CN101631770A - The compound that suppresses Pseudocholinesterase - Google Patents
The compound that suppresses Pseudocholinesterase Download PDFInfo
- Publication number
- CN101631770A CN101631770A CN200880007756A CN200880007756A CN101631770A CN 101631770 A CN101631770 A CN 101631770A CN 200880007756 A CN200880007756 A CN 200880007756A CN 200880007756 A CN200880007756 A CN 200880007756A CN 101631770 A CN101631770 A CN 101631770A
- Authority
- CN
- China
- Prior art keywords
- hydrogen
- compound
- pharmacological activity
- refers
- structural formula
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 374
- 108010053652 Butyrylcholinesterase Proteins 0.000 title claims description 80
- 102000021944 Butyrylcholinesterase Human genes 0.000 title 1
- 230000000694 effects Effects 0.000 claims abstract description 70
- 230000001713 cholinergic effect Effects 0.000 claims abstract description 36
- 230000008034 disappearance Effects 0.000 claims abstract description 26
- 201000010099 disease Diseases 0.000 claims abstract description 26
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 26
- 230000000926 neurological effect Effects 0.000 claims abstract description 15
- 239000001257 hydrogen Substances 0.000 claims description 510
- 229910052739 hydrogen Inorganic materials 0.000 claims description 510
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 341
- 150000002431 hydrogen Chemical class 0.000 claims description 166
- 102100032404 Cholinesterase Human genes 0.000 claims description 92
- 230000006378 damage Effects 0.000 claims description 89
- 230000015654 memory Effects 0.000 claims description 75
- 238000011282 treatment Methods 0.000 claims description 63
- GGRLKHMFMUXIOG-UHFFFAOYSA-M 2-acetyloxyethyl(trimethyl)azanium;hydroxide Chemical compound [OH-].CC(=O)OCC[N+](C)(C)C GGRLKHMFMUXIOG-UHFFFAOYSA-M 0.000 claims description 62
- -1 sec.-propyl Chemical group 0.000 claims description 57
- 239000003814 drug Substances 0.000 claims description 50
- 125000000217 alkyl group Chemical group 0.000 claims description 45
- 102100033639 Acetylcholinesterase Human genes 0.000 claims description 43
- 108010022752 Acetylcholinesterase Proteins 0.000 claims description 43
- 229940022698 acetylcholinesterase Drugs 0.000 claims description 43
- 208000027418 Wounds and injury Diseases 0.000 claims description 40
- 208000014674 injury Diseases 0.000 claims description 40
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 34
- 230000003920 cognitive function Effects 0.000 claims description 33
- 208000024827 Alzheimer disease Diseases 0.000 claims description 28
- 239000000812 cholinergic antagonist Substances 0.000 claims description 27
- 229940121948 Muscarinic receptor antagonist Drugs 0.000 claims description 21
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 20
- 210000001428 peripheral nervous system Anatomy 0.000 claims description 20
- 238000002360 preparation method Methods 0.000 claims description 20
- 208000002193 Pain Diseases 0.000 claims description 19
- 208000015114 central nervous system disease Diseases 0.000 claims description 19
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 claims description 18
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 claims description 18
- 208000018737 Parkinson disease Diseases 0.000 claims description 18
- 150000003839 salts Chemical class 0.000 claims description 17
- 206010008190 Cerebrovascular accident Diseases 0.000 claims description 16
- 206010021518 Impaired gastric emptying Diseases 0.000 claims description 16
- 241000208125 Nicotiana Species 0.000 claims description 16
- 235000002637 Nicotiana tabacum Nutrition 0.000 claims description 16
- 206010034912 Phobia Diseases 0.000 claims description 16
- 208000006011 Stroke Diseases 0.000 claims description 16
- 208000019899 phobic disease Diseases 0.000 claims description 16
- 201000006417 multiple sclerosis Diseases 0.000 claims description 13
- 229910052698 phosphorus Inorganic materials 0.000 claims description 13
- 239000008194 pharmaceutical composition Substances 0.000 claims description 12
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 claims description 11
- 229960004373 acetylcholine Drugs 0.000 claims description 11
- 208000012219 Autonomic Nervous System disease Diseases 0.000 claims description 10
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 10
- 229910052717 sulfur Inorganic materials 0.000 claims description 9
- 239000002329 esterase inhibitor Substances 0.000 claims description 8
- 230000006403 short-term memory Effects 0.000 claims description 8
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 8
- 241000894006 Bacteria Species 0.000 claims description 7
- 208000010412 Glaucoma Diseases 0.000 claims description 7
- 206010028980 Neoplasm Diseases 0.000 claims description 7
- 206010020751 Hypersensitivity Diseases 0.000 claims description 6
- 208000027530 Meniere disease Diseases 0.000 claims description 6
- 208000008238 Muscle Spasticity Diseases 0.000 claims description 6
- 208000026935 allergic disease Diseases 0.000 claims description 6
- 230000007815 allergy Effects 0.000 claims description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
- 208000018198 spasticity Diseases 0.000 claims description 6
- 230000009385 viral infection Effects 0.000 claims description 6
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 5
- 241001289721 Lethe Species 0.000 claims description 5
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 5
- 230000007787 long-term memory Effects 0.000 claims description 4
- 239000003153 chemical reaction reagent Substances 0.000 abstract description 491
- 230000000144 pharmacologic effect Effects 0.000 abstract description 405
- 238000006460 hydrolysis reaction Methods 0.000 abstract description 35
- 230000007062 hydrolysis Effects 0.000 abstract description 25
- 108090000322 Cholinesterases Proteins 0.000 abstract description 4
- 229940048961 cholinesterase Drugs 0.000 abstract description 4
- 102000003914 Cholinesterases Human genes 0.000 abstract 1
- 238000000034 method Methods 0.000 description 108
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 62
- VIKNJXKGJWUCNN-XGXHKTLJSA-N norethisterone Chemical compound O=C1CC[C@@H]2[C@H]3CC[C@](C)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=C1 VIKNJXKGJWUCNN-XGXHKTLJSA-N 0.000 description 38
- 210000004027 cell Anatomy 0.000 description 37
- 241000700159 Rattus Species 0.000 description 35
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 34
- 238000012360 testing method Methods 0.000 description 32
- 239000000243 solution Substances 0.000 description 31
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 29
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 29
- 210000001519 tissue Anatomy 0.000 description 29
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 28
- 150000001412 amines Chemical class 0.000 description 27
- 239000003795 chemical substances by application Substances 0.000 description 26
- 239000002858 neurotransmitter agent Substances 0.000 description 25
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 24
- KXDHJXZQYSOELW-UHFFFAOYSA-N Carbamic acid Chemical compound NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 description 24
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 24
- 229960002748 norepinephrine Drugs 0.000 description 24
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 24
- 230000005540 biological transmission Effects 0.000 description 23
- 210000004556 brain Anatomy 0.000 description 20
- 210000003169 central nervous system Anatomy 0.000 description 20
- 210000002569 neuron Anatomy 0.000 description 20
- 239000000825 pharmaceutical preparation Substances 0.000 description 20
- 230000005764 inhibitory process Effects 0.000 description 18
- 108090000371 Esterases Proteins 0.000 description 17
- 230000003301 hydrolyzing effect Effects 0.000 description 17
- 230000003750 conditioning effect Effects 0.000 description 15
- 239000003112 inhibitor Substances 0.000 description 15
- OGNSCSPNOLGXSM-UHFFFAOYSA-N (+/-)-DABA Natural products NCCC(N)C(O)=O OGNSCSPNOLGXSM-UHFFFAOYSA-N 0.000 description 14
- 108020002739 Catechol O-methyltransferase Proteins 0.000 description 14
- 102000006378 Catechol O-methyltransferase Human genes 0.000 description 14
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 14
- 229960003692 gamma aminobutyric acid Drugs 0.000 description 14
- 239000000523 sample Substances 0.000 description 14
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 13
- 239000005557 antagonist Substances 0.000 description 13
- 229960002989 glutamic acid Drugs 0.000 description 13
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 12
- PIJVFDBKTWXHHD-UHFFFAOYSA-N Physostigmine Natural products C12=CC(OC(=O)NC)=CC=C2N(C)C2C1(C)CCN2C PIJVFDBKTWXHHD-UHFFFAOYSA-N 0.000 description 12
- 238000001514 detection method Methods 0.000 description 12
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 12
- 230000003291 dopaminomimetic effect Effects 0.000 description 12
- 229960001697 physostigmine Drugs 0.000 description 12
- 230000008569 process Effects 0.000 description 12
- 239000000047 product Substances 0.000 description 12
- HOKKHZGPKSLGJE-VKHMYHEASA-N (2s)-2-(methylamino)butanedioic acid Chemical compound CN[C@H](C(O)=O)CC(O)=O HOKKHZGPKSLGJE-VKHMYHEASA-N 0.000 description 11
- CTENFNNZBMHDDG-UHFFFAOYSA-N Dopamine hydrochloride Chemical compound Cl.NCCC1=CC=C(O)C(O)=C1 CTENFNNZBMHDDG-UHFFFAOYSA-N 0.000 description 11
- 102000004190 Enzymes Human genes 0.000 description 11
- 108090000790 Enzymes Proteins 0.000 description 11
- HOKKHZGPKSLGJE-UHFFFAOYSA-N N-methyl-D-aspartic acid Natural products CNC(C(O)=O)CC(O)=O HOKKHZGPKSLGJE-UHFFFAOYSA-N 0.000 description 11
- 239000000556 agonist Substances 0.000 description 11
- STECJAGHUSJQJN-VJQRDGCPSA-N chembl3084722 Chemical compound C1([C@@H](CO)C(=O)O[C@@H]2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 STECJAGHUSJQJN-VJQRDGCPSA-N 0.000 description 11
- 229940088598 enzyme Drugs 0.000 description 11
- 210000003205 muscle Anatomy 0.000 description 11
- PIJVFDBKTWXHHD-HIFRSBDPSA-N physostigmine Chemical compound C12=CC(OC(=O)NC)=CC=C2N(C)[C@@H]2[C@@]1(C)CCN2C PIJVFDBKTWXHHD-HIFRSBDPSA-N 0.000 description 11
- 102000005962 receptors Human genes 0.000 description 11
- 108020003175 receptors Proteins 0.000 description 11
- 229960002646 scopolamine Drugs 0.000 description 11
- 208000024891 symptom Diseases 0.000 description 11
- 101710083761 Cholinesterase Proteins 0.000 description 10
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 10
- 239000013543 active substance Substances 0.000 description 10
- 230000001800 adrenalinergic effect Effects 0.000 description 10
- 125000003118 aryl group Chemical group 0.000 description 10
- 229940079593 drug Drugs 0.000 description 10
- 239000007789 gas Substances 0.000 description 10
- 230000001242 postsynaptic effect Effects 0.000 description 10
- 229930000680 A04AD01 - Scopolamine Natural products 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
- STECJAGHUSJQJN-GAUPFVANSA-N Hyoscine Natural products C1([C@H](CO)C(=O)OC2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 STECJAGHUSJQJN-GAUPFVANSA-N 0.000 description 9
- STECJAGHUSJQJN-UHFFFAOYSA-N N-Methyl-scopolamin Natural products C1C(C2C3O2)N(C)C3CC1OC(=O)C(CO)C1=CC=CC=C1 STECJAGHUSJQJN-UHFFFAOYSA-N 0.000 description 9
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 9
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 9
- 239000002253 acid Substances 0.000 description 9
- 210000003403 autonomic nervous system Anatomy 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 9
- 239000002504 physiological saline solution Substances 0.000 description 9
- UCTWMZQNUQWSLP-VIFPVBQESA-N (R)-adrenaline Chemical compound CNC[C@H](O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-VIFPVBQESA-N 0.000 description 8
- HCYAFALTSJYZDH-UHFFFAOYSA-N Desimpramine Chemical compound C1CC2=CC=CC=C2N(CCCNC)C2=CC=CC=C21 HCYAFALTSJYZDH-UHFFFAOYSA-N 0.000 description 8
- 239000004471 Glycine Substances 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 8
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 8
- 239000002585 base Substances 0.000 description 8
- MYSWGUAQZAJSOK-UHFFFAOYSA-N ciprofloxacin Chemical compound C12=CC(N3CCNCC3)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 MYSWGUAQZAJSOK-UHFFFAOYSA-N 0.000 description 8
- 229960003914 desipramine Drugs 0.000 description 8
- 229960005139 epinephrine Drugs 0.000 description 8
- 238000004128 high performance liquid chromatography Methods 0.000 description 8
- 239000000463 material Substances 0.000 description 8
- 230000000862 serotonergic effect Effects 0.000 description 8
- FDDDEECHVMSUSB-UHFFFAOYSA-N sulfanilamide Chemical compound NC1=CC=C(S(N)(=O)=O)C=C1 FDDDEECHVMSUSB-UHFFFAOYSA-N 0.000 description 8
- 229940124530 sulfonamide Drugs 0.000 description 8
- AHOUBRCZNHFOSL-YOEHRIQHSA-N (+)-Casbol Chemical compound C1=CC(F)=CC=C1[C@H]1[C@H](COC=2C=C3OCOC3=CC=2)CNCC1 AHOUBRCZNHFOSL-YOEHRIQHSA-N 0.000 description 7
- WTDRDQBEARUVNC-LURJTMIESA-N L-DOPA Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-LURJTMIESA-N 0.000 description 7
- WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 description 7
- 102000016193 Metabotropic glutamate receptors Human genes 0.000 description 7
- 108010010914 Metabotropic glutamate receptors Proteins 0.000 description 7
- AHOUBRCZNHFOSL-UHFFFAOYSA-N Paroxetine hydrochloride Natural products C1=CC(F)=CC=C1C1C(COC=2C=C3OCOC3=CC=2)CNCC1 AHOUBRCZNHFOSL-UHFFFAOYSA-N 0.000 description 7
- ASNFTDCKZKHJSW-REOHCLBHSA-N Quisqualic acid Chemical compound OC(=O)[C@@H](N)CN1OC(=O)NC1=O ASNFTDCKZKHJSW-REOHCLBHSA-N 0.000 description 7
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 7
- 229960004038 fluvoxamine Drugs 0.000 description 7
- CJOFXWAVKWHTFT-XSFVSMFZSA-N fluvoxamine Chemical compound COCCCC\C(=N/OCCN)C1=CC=C(C(F)(F)F)C=C1 CJOFXWAVKWHTFT-XSFVSMFZSA-N 0.000 description 7
- JUMYIBMBTDDLNG-OJERSXHUSA-N hydron;methyl (2r)-2-phenyl-2-[(2r)-piperidin-2-yl]acetate;chloride Chemical compound Cl.C([C@@H]1[C@H](C(=O)OC)C=2C=CC=CC=2)CCCN1 JUMYIBMBTDDLNG-OJERSXHUSA-N 0.000 description 7
- 239000007924 injection Substances 0.000 description 7
- 238000002347 injection Methods 0.000 description 7
- 229960004502 levodopa Drugs 0.000 description 7
- 239000000203 mixture Substances 0.000 description 7
- 229960002296 paroxetine Drugs 0.000 description 7
- BWPIARFWQZKAIA-UHFFFAOYSA-N protriptyline Chemical compound C1=CC2=CC=CC=C2C(CCCNC)C2=CC=CC=C21 BWPIARFWQZKAIA-UHFFFAOYSA-N 0.000 description 7
- 229960002601 protriptyline Drugs 0.000 description 7
- 229940099204 ritalin Drugs 0.000 description 7
- VGKDLMBJGBXTGI-SJCJKPOMSA-N sertraline Chemical compound C1([C@@H]2CC[C@@H](C3=CC=CC=C32)NC)=CC=C(Cl)C(Cl)=C1 VGKDLMBJGBXTGI-SJCJKPOMSA-N 0.000 description 7
- 229960002073 sertraline Drugs 0.000 description 7
- 210000002027 skeletal muscle Anatomy 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- ZEUITGRIYCTCEM-KRWDZBQOSA-N (S)-duloxetine Chemical compound C1([C@@H](OC=2C3=CC=CC=C3C=CC=2)CCNC)=CC=CS1 ZEUITGRIYCTCEM-KRWDZBQOSA-N 0.000 description 6
- 102000009346 Adenosine receptors Human genes 0.000 description 6
- 108050000203 Adenosine receptors Proteins 0.000 description 6
- 208000019901 Anxiety disease Diseases 0.000 description 6
- KPYSYYIEGFHWSV-UHFFFAOYSA-N Baclofen Chemical compound OC(=O)CC(CN)C1=CC=C(Cl)C=C1 KPYSYYIEGFHWSV-UHFFFAOYSA-N 0.000 description 6
- UGJMXCAKCUNAIE-UHFFFAOYSA-N Gabapentin Chemical compound OC(=O)CC1(CN)CCCCC1 UGJMXCAKCUNAIE-UHFFFAOYSA-N 0.000 description 6
- PHVGLTMQBUFIQQ-UHFFFAOYSA-N Nortryptiline Chemical compound C1CC2=CC=CC=C2C(=CCCNC)C2=CC=CC=C21 PHVGLTMQBUFIQQ-UHFFFAOYSA-N 0.000 description 6
- 206010039424 Salivary hypersecretion Diseases 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 238000010521 absorption reaction Methods 0.000 description 6
- 239000000783 alginic acid Substances 0.000 description 6
- 235000010443 alginic acid Nutrition 0.000 description 6
- 229920000615 alginic acid Polymers 0.000 description 6
- 229960001126 alginic acid Drugs 0.000 description 6
- 150000004781 alginic acids Chemical class 0.000 description 6
- QWGDMFLQWFTERH-UHFFFAOYSA-N amoxapine Chemical compound C12=CC(Cl)=CC=C2OC2=CC=CC=C2N=C1N1CCNCC1 QWGDMFLQWFTERH-UHFFFAOYSA-N 0.000 description 6
- 229960002519 amoxapine Drugs 0.000 description 6
- RXDALBZNGVATNY-CWLIKTDRSA-N ampicillin trihydrate Chemical compound O.O.O.C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 RXDALBZNGVATNY-CWLIKTDRSA-N 0.000 description 6
- 229960003311 ampicillin trihydrate Drugs 0.000 description 6
- 229960000794 baclofen Drugs 0.000 description 6
- UUQMNUMQCIQDMZ-UHFFFAOYSA-N betahistine Chemical compound CNCCC1=CC=CC=N1 UUQMNUMQCIQDMZ-UHFFFAOYSA-N 0.000 description 6
- 229960004536 betahistine Drugs 0.000 description 6
- KDJVUTSOHYQCDQ-UHFFFAOYSA-N carbamic acid;1h-imidazole Chemical class NC([O-])=O.[NH2+]1C=CN=C1 KDJVUTSOHYQCDQ-UHFFFAOYSA-N 0.000 description 6
- 125000004432 carbon atom Chemical group C* 0.000 description 6
- 230000008859 change Effects 0.000 description 6
- 238000013016 damping Methods 0.000 description 6
- 230000000994 depressogenic effect Effects 0.000 description 6
- 229960002866 duloxetine Drugs 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 6
- 239000012530 fluid Substances 0.000 description 6
- 230000006870 function Effects 0.000 description 6
- 229960001340 histamine Drugs 0.000 description 6
- 229940125425 inverse agonist Drugs 0.000 description 6
- 210000004165 myocardium Anatomy 0.000 description 6
- SYJXFKPQNSDJLI-HKEUSBCWSA-N neamine Chemical compound N[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](N)C[C@@H]1N SYJXFKPQNSDJLI-HKEUSBCWSA-N 0.000 description 6
- 230000001537 neural effect Effects 0.000 description 6
- 229960001158 nortriptyline Drugs 0.000 description 6
- 210000005215 presynaptic neuron Anatomy 0.000 description 6
- 235000019260 propionic acid Nutrition 0.000 description 6
- 230000009467 reduction Effects 0.000 description 6
- 208000026451 salivation Diseases 0.000 description 6
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 6
- PFNFFQXMRSDOHW-UHFFFAOYSA-N spermine Chemical compound NCCCNCCCCNCCCN PFNFFQXMRSDOHW-UHFFFAOYSA-N 0.000 description 6
- 108010013043 Acetylesterase Proteins 0.000 description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 5
- 206010020772 Hypertension Diseases 0.000 description 5
- 102000010909 Monoamine Oxidase Human genes 0.000 description 5
- 108010062431 Monoamine oxidase Proteins 0.000 description 5
- 229940087098 Oxidase inhibitor Drugs 0.000 description 5
- 230000004913 activation Effects 0.000 description 5
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 5
- DKNWSYNQZKUICI-UHFFFAOYSA-N amantadine Chemical compound C1C(C2)CC3CC2CC1(N)C3 DKNWSYNQZKUICI-UHFFFAOYSA-N 0.000 description 5
- 229960000528 amlodipine Drugs 0.000 description 5
- HTIQEAQVCYTUBX-UHFFFAOYSA-N amlodipine Chemical compound CCOC(=O)C1=C(COCCN)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1Cl HTIQEAQVCYTUBX-UHFFFAOYSA-N 0.000 description 5
- 235000003704 aspartic acid Nutrition 0.000 description 5
- VHGCDTVCOLNTBX-QGZVFWFLSA-N atomoxetine Chemical compound O([C@H](CCNC)C=1C=CC=CC=1)C1=CC=CC=C1C VHGCDTVCOLNTBX-QGZVFWFLSA-N 0.000 description 5
- 229960002430 atomoxetine Drugs 0.000 description 5
- 239000002439 beta secretase inhibitor Substances 0.000 description 5
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 5
- 229910052799 carbon Inorganic materials 0.000 description 5
- 239000000064 cholinergic agonist Substances 0.000 description 5
- 230000021615 conjugation Effects 0.000 description 5
- 238000005516 engineering process Methods 0.000 description 5
- 239000003540 gamma secretase inhibitor Substances 0.000 description 5
- 239000004615 ingredient Substances 0.000 description 5
- 238000005259 measurement Methods 0.000 description 5
- 230000001404 mediated effect Effects 0.000 description 5
- 230000003551 muscarinic effect Effects 0.000 description 5
- 210000000663 muscle cell Anatomy 0.000 description 5
- 239000002767 noradrenalin uptake inhibitor Substances 0.000 description 5
- 229940126569 noradrenaline reuptake inhibitor Drugs 0.000 description 5
- 150000003141 primary amines Chemical class 0.000 description 5
- 229940002612 prodrug Drugs 0.000 description 5
- 239000000651 prodrug Substances 0.000 description 5
- 238000011160 research Methods 0.000 description 5
- 238000012216 screening Methods 0.000 description 5
- 239000000758 substrate Substances 0.000 description 5
- 238000012549 training Methods 0.000 description 5
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 5
- 239000003981 vehicle Substances 0.000 description 5
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 description 4
- RTHCYVBBDHJXIQ-MRXNPFEDSA-N (R)-fluoxetine Chemical compound O([C@H](CCNC)C=1C=CC=CC=1)C1=CC=C(C(F)(F)F)C=C1 RTHCYVBBDHJXIQ-MRXNPFEDSA-N 0.000 description 4
- UBCHPRBFMUDMNC-UHFFFAOYSA-N 1-(1-adamantyl)ethanamine Chemical compound C1C(C2)CC3CC2CC1(C(N)C)C3 UBCHPRBFMUDMNC-UHFFFAOYSA-N 0.000 description 4
- 208000000044 Amnesia Diseases 0.000 description 4
- 208000031091 Amnestic disease Diseases 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 4
- 229940122739 Calcineurin inhibitor Drugs 0.000 description 4
- 101710192106 Calcineurin-binding protein cabin-1 Proteins 0.000 description 4
- 102100024123 Calcineurin-binding protein cabin-1 Human genes 0.000 description 4
- 241000218236 Cannabis Species 0.000 description 4
- 108010065152 Coagulase Proteins 0.000 description 4
- ASNFTDCKZKHJSW-UHFFFAOYSA-N DL-Quisqualic acid Natural products OC(=O)C(N)CN1OC(=O)NC1=O ASNFTDCKZKHJSW-UHFFFAOYSA-N 0.000 description 4
- MQJKPEGWNLWLTK-UHFFFAOYSA-N Dapsone Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=C1 MQJKPEGWNLWLTK-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- RPTUSVTUFVMDQK-UHFFFAOYSA-N Hidralazin Chemical compound C1=CC=C2C(NN)=NN=CC2=C1 RPTUSVTUFVMDQK-UHFFFAOYSA-N 0.000 description 4
- 102000004310 Ion Channels Human genes 0.000 description 4
- 108090000862 Ion Channels Proteins 0.000 description 4
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 4
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 4
- 206010029897 Obsessive thoughts Diseases 0.000 description 4
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 4
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 241000191940 Staphylococcus Species 0.000 description 4
- NHUHCSRWZMLRLA-UHFFFAOYSA-N Sulfisoxazole Chemical compound CC1=NOC(NS(=O)(=O)C=2C=CC(N)=CC=2)=C1C NHUHCSRWZMLRLA-UHFFFAOYSA-N 0.000 description 4
- 102000016981 Trace amine receptors Human genes 0.000 description 4
- 108070000027 Trace amine receptors Proteins 0.000 description 4
- 239000007983 Tris buffer Substances 0.000 description 4
- HDOVUKNUBWVHOX-QMMMGPOBSA-N Valacyclovir Chemical compound N1C(N)=NC(=O)C2=C1N(COCCOC(=O)[C@@H](N)C(C)C)C=N2 HDOVUKNUBWVHOX-QMMMGPOBSA-N 0.000 description 4
- WREGKURFCTUGRC-POYBYMJQSA-N Zalcitabine Chemical compound O=C1N=C(N)C=CN1[C@@H]1O[C@H](CO)CC1 WREGKURFCTUGRC-POYBYMJQSA-N 0.000 description 4
- 230000009471 action Effects 0.000 description 4
- 229960005305 adenosine Drugs 0.000 description 4
- 230000006986 amnesia Effects 0.000 description 4
- 230000006399 behavior Effects 0.000 description 4
- BLFLLBZGZJTVJG-UHFFFAOYSA-N benzocaine Chemical compound CCOC(=O)C1=CC=C(N)C=C1 BLFLLBZGZJTVJG-UHFFFAOYSA-N 0.000 description 4
- 230000036760 body temperature Effects 0.000 description 4
- 230000003925 brain function Effects 0.000 description 4
- 229960001701 chloroform Drugs 0.000 description 4
- 229960003405 ciprofloxacin Drugs 0.000 description 4
- 230000019771 cognition Effects 0.000 description 4
- 230000001149 cognitive effect Effects 0.000 description 4
- 229960000860 dapsone Drugs 0.000 description 4
- 230000009849 deactivation Effects 0.000 description 4
- 238000000354 decomposition reaction Methods 0.000 description 4
- 230000007423 decrease Effects 0.000 description 4
- WHBIGIKBNXZKFE-UHFFFAOYSA-N delavirdine Chemical compound CC(C)NC1=CC=CN=C1N1CCN(C(=O)C=2NC3=CC=C(NS(C)(=O)=O)C=C3C=2)CC1 WHBIGIKBNXZKFE-UHFFFAOYSA-N 0.000 description 4
- 230000006866 deterioration Effects 0.000 description 4
- 210000003499 exocrine gland Anatomy 0.000 description 4
- 229960002464 fluoxetine Drugs 0.000 description 4
- 210000004907 gland Anatomy 0.000 description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 229930182817 methionine Natural products 0.000 description 4
- 239000011259 mixed solution Substances 0.000 description 4
- 238000012544 monitoring process Methods 0.000 description 4
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 4
- 229960002715 nicotine Drugs 0.000 description 4
- 239000002664 nootropic agent Substances 0.000 description 4
- 230000001777 nootropic effect Effects 0.000 description 4
- FASDKYOPVNHBLU-ZETCQYMHSA-N pramipexole Chemical compound C1[C@@H](NCCC)CCC2=C1SC(N)=N2 FASDKYOPVNHBLU-ZETCQYMHSA-N 0.000 description 4
- AYXYPKUFHZROOJ-ZETCQYMHSA-N pregabalin Chemical compound CC(C)C[C@H](CN)CC(O)=O AYXYPKUFHZROOJ-ZETCQYMHSA-N 0.000 description 4
- 108090000765 processed proteins & peptides Proteins 0.000 description 4
- 125000003226 pyrazolyl group Chemical group 0.000 description 4
- 229940044551 receptor antagonist Drugs 0.000 description 4
- 239000002464 receptor antagonist Substances 0.000 description 4
- 230000000452 restraining effect Effects 0.000 description 4
- 229960000888 rimantadine Drugs 0.000 description 4
- 150000003335 secondary amines Chemical class 0.000 description 4
- 229940099992 seromycin Drugs 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- 229960001866 silicon dioxide Drugs 0.000 description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 description 4
- 229910000029 sodium carbonate Inorganic materials 0.000 description 4
- 229960000654 sulfafurazole Drugs 0.000 description 4
- 229940093257 valacyclovir Drugs 0.000 description 4
- 229960000523 zalcitabine Drugs 0.000 description 4
- IGLYMJRIWWIQQE-QUOODJBBSA-N (1S,2R)-2-phenylcyclopropan-1-amine (1R,2S)-2-phenylcyclopropan-1-amine Chemical compound N[C@H]1C[C@@H]1C1=CC=CC=C1.N[C@@H]1C[C@H]1C1=CC=CC=C1 IGLYMJRIWWIQQE-QUOODJBBSA-N 0.000 description 3
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 3
- SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 description 3
- UIAGMCDKSXEBJQ-IBGZPJMESA-N 3-o-(2-methoxyethyl) 5-o-propan-2-yl (4s)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound COCCOC(=O)C1=C(C)NC(C)=C(C(=O)OC(C)C)[C@H]1C1=CC=CC([N+]([O-])=O)=C1 UIAGMCDKSXEBJQ-IBGZPJMESA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- OGSPWJRAVKPPFI-UHFFFAOYSA-N Alendronic Acid Chemical compound NCCCC(O)(P(O)(O)=O)P(O)(O)=O OGSPWJRAVKPPFI-UHFFFAOYSA-N 0.000 description 3
- XYLJNLCSTIOKRM-UHFFFAOYSA-N Alphagan Chemical compound C1=CC2=NC=CN=C2C(Br)=C1NC1=NCCN1 XYLJNLCSTIOKRM-UHFFFAOYSA-N 0.000 description 3
- 229940127291 Calcium channel antagonist Drugs 0.000 description 3
- CKDWPUIZGOQOOM-UHFFFAOYSA-N Carbamyl chloride Chemical compound NC(Cl)=O CKDWPUIZGOQOOM-UHFFFAOYSA-N 0.000 description 3
- 108010009685 Cholinergic Receptors Proteins 0.000 description 3
- 208000000094 Chronic Pain Diseases 0.000 description 3
- JRWZLRBJNMZMFE-UHFFFAOYSA-N Dobutamine Chemical compound C=1C=C(O)C(O)=CC=1CCNC(C)CCC1=CC=C(O)C=C1 JRWZLRBJNMZMFE-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- LFMYNZPAVPMEGP-PIDGMYBPSA-N Fluvoxamine maleate Chemical compound OC(=O)\C=C/C(O)=O.COCCCC\C(=N/OCCN)C1=CC=C(C(F)(F)F)C=C1 LFMYNZPAVPMEGP-PIDGMYBPSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 102000004257 Potassium Channel Human genes 0.000 description 3
- 229940127316 Potassium Channel Antagonists Drugs 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 3
- FTALBRSUTCGOEG-UHFFFAOYSA-N Riluzole Chemical compound C1=C(OC(F)(F)F)C=C2SC(N)=NC2=C1 FTALBRSUTCGOEG-UHFFFAOYSA-N 0.000 description 3
- 206010066218 Stress Urinary Incontinence Diseases 0.000 description 3
- 102000034337 acetylcholine receptors Human genes 0.000 description 3
- 229940049706 benzodiazepine Drugs 0.000 description 3
- 230000008236 biological pathway Effects 0.000 description 3
- 229960003679 brimonidine Drugs 0.000 description 3
- 239000000480 calcium channel blocker Substances 0.000 description 3
- 230000006949 cholinergic function Effects 0.000 description 3
- 238000004737 colorimetric analysis Methods 0.000 description 3
- 238000006114 decarboxylation reaction Methods 0.000 description 3
- 229960001089 dobutamine Drugs 0.000 description 3
- IAVUPMFITXYVAF-XPUUQOCRSA-N dorzolamide Chemical compound CCN[C@H]1C[C@H](C)S(=O)(=O)C2=C1C=C(S(N)(=O)=O)S2 IAVUPMFITXYVAF-XPUUQOCRSA-N 0.000 description 3
- 229960003933 dorzolamide Drugs 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 230000009977 dual effect Effects 0.000 description 3
- 210000002919 epithelial cell Anatomy 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 230000003203 everyday effect Effects 0.000 description 3
- 229960002107 fluvoxamine maleate Drugs 0.000 description 3
- 229960002870 gabapentin Drugs 0.000 description 3
- 239000003823 glutamate receptor agonist Substances 0.000 description 3
- 239000003825 glutamate receptor antagonist Substances 0.000 description 3
- 125000005842 heteroatom Chemical group 0.000 description 3
- 229940088597 hormone Drugs 0.000 description 3
- 239000005556 hormone Substances 0.000 description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 3
- 239000012948 isocyanate Substances 0.000 description 3
- 150000002513 isocyanates Chemical class 0.000 description 3
- PYZRQGJRPPTADH-UHFFFAOYSA-N lamotrigine Chemical compound NC1=NC(N)=NN=C1C1=CC=CC(Cl)=C1Cl PYZRQGJRPPTADH-UHFFFAOYSA-N 0.000 description 3
- 229960001848 lamotrigine Drugs 0.000 description 3
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 3
- 229960003088 loratadine Drugs 0.000 description 3
- JCCNYMKQOSZNPW-UHFFFAOYSA-N loratadine Chemical compound C1CN(C(=O)OCC)CCC1=C1C2=NC=CC=C2CCC2=CC(Cl)=CC=C21 JCCNYMKQOSZNPW-UHFFFAOYSA-N 0.000 description 3
- 229940009697 lyrica Drugs 0.000 description 3
- 125000004674 methylcarbonyl group Chemical group CC(=O)* 0.000 description 3
- 238000002715 modification method Methods 0.000 description 3
- ZJQHPWUVQPJPQT-UHFFFAOYSA-N muscimol Chemical compound NCC1=CC(=O)NO1 ZJQHPWUVQPJPQT-UHFFFAOYSA-N 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 229930014626 natural product Natural products 0.000 description 3
- 210000005036 nerve Anatomy 0.000 description 3
- 229960000715 nimodipine Drugs 0.000 description 3
- 210000000056 organ Anatomy 0.000 description 3
- 210000001002 parasympathetic nervous system Anatomy 0.000 description 3
- 230000037361 pathway Effects 0.000 description 3
- 229960004851 pergolide Drugs 0.000 description 3
- YEHCICAEULNIGD-MZMPZRCHSA-N pergolide Chemical compound C1=CC([C@H]2C[C@@H](CSC)CN([C@@H]2C2)CCC)=C3C2=CNC3=C1 YEHCICAEULNIGD-MZMPZRCHSA-N 0.000 description 3
- 108020001213 potassium channel Proteins 0.000 description 3
- 229960003089 pramipexole Drugs 0.000 description 3
- 239000002243 precursor Substances 0.000 description 3
- 230000002265 prevention Effects 0.000 description 3
- 238000012545 processing Methods 0.000 description 3
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical group CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 3
- 230000001105 regulatory effect Effects 0.000 description 3
- 229960004181 riluzole Drugs 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 230000019491 signal transduction Effects 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 229940063675 spermine Drugs 0.000 description 3
- 210000000278 spinal cord Anatomy 0.000 description 3
- 208000022170 stress incontinence Diseases 0.000 description 3
- 210000002820 sympathetic nervous system Anatomy 0.000 description 3
- 230000000946 synaptic effect Effects 0.000 description 3
- 229960003741 tranylcypromine Drugs 0.000 description 3
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 3
- 230000003313 weakening effect Effects 0.000 description 3
- JWZZKOKVBUJMES-UHFFFAOYSA-N (+-)-Isoprenaline Chemical compound CC(C)NCC(O)C1=CC=C(O)C(O)=C1 JWZZKOKVBUJMES-UHFFFAOYSA-N 0.000 description 2
- HMJIYCCIJYRONP-UHFFFAOYSA-N (+-)-Isradipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC(C)C)C1C1=CC=CC2=NON=C12 HMJIYCCIJYRONP-UHFFFAOYSA-N 0.000 description 2
- KWGRBVOPPLSCSI-WPRPVWTQSA-N (-)-ephedrine Chemical compound CN[C@@H](C)[C@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-WPRPVWTQSA-N 0.000 description 2
- FERIKTBTNCSGJS-OBLUMXEWSA-N (1r,2s)-4-aminocyclopentane-1,2,4-tricarboxylic acid Chemical compound OC(=O)C1(N)C[C@H](C(O)=O)[C@H](C(O)=O)C1 FERIKTBTNCSGJS-OBLUMXEWSA-N 0.000 description 2
- IRJCBFDCFXCWGO-BYPYZUCNSA-N (2s)-2-amino-2-(3-oxo-1,2-oxazol-5-yl)acetic acid Chemical compound OC(=O)[C@@H](N)C1=CC(=O)NO1 IRJCBFDCFXCWGO-BYPYZUCNSA-N 0.000 description 2
- YKFCISHFRZHKHY-NGQGLHOPSA-N (2s)-2-amino-3-(3,4-dihydroxyphenyl)-2-methylpropanoic acid;trihydrate Chemical compound O.O.O.OC(=O)[C@](N)(C)CC1=CC=C(O)C(O)=C1.OC(=O)[C@](N)(C)CC1=CC=C(O)C(O)=C1 YKFCISHFRZHKHY-NGQGLHOPSA-N 0.000 description 2
- OOBHFESNSZDWIU-GXSJLCMTSA-N (2s,3s)-3-methyl-2-phenylmorpholine Chemical compound C[C@@H]1NCCO[C@H]1C1=CC=CC=C1 OOBHFESNSZDWIU-GXSJLCMTSA-N 0.000 description 2
- KRKRAOXTGDJWNI-DMTCNVIQSA-N (2s,4r)-2-amino-4-methylpentanedioic acid Chemical compound OC(=O)[C@H](C)C[C@H](N)C(O)=O KRKRAOXTGDJWNI-DMTCNVIQSA-N 0.000 description 2
- NXLNNXIXOYSCMB-UHFFFAOYSA-N (4-nitrophenyl) carbonochloridate Chemical compound [O-][N+](=O)C1=CC=C(OC(Cl)=O)C=C1 NXLNNXIXOYSCMB-UHFFFAOYSA-N 0.000 description 2
- BGOQGUHWXBGXJW-YOEHRIQHSA-N (6as,12br)-5,6,6a,7,8,12b-hexahydrobenzo[a]phenanthridine-10,11-diol Chemical compound N1CC2=CC=CC=C2[C@@H]2[C@@H]1CCC1=C2C=C(O)C(O)=C1 BGOQGUHWXBGXJW-YOEHRIQHSA-N 0.000 description 2
- MTXSIJUGVMTTMU-JTQLQIEISA-N (S)-anabasine Chemical compound N1CCCC[C@H]1C1=CC=CN=C1 MTXSIJUGVMTTMU-JTQLQIEISA-N 0.000 description 2
- XUBOMFCQGDBHNK-JTQLQIEISA-N (S)-gatifloxacin Chemical compound FC1=CC(C(C(C(O)=O)=CN2C3CC3)=O)=C2C(OC)=C1N1CCN[C@@H](C)C1 XUBOMFCQGDBHNK-JTQLQIEISA-N 0.000 description 2
- MGRVRXRGTBOSHW-UHFFFAOYSA-N (aminomethyl)phosphonic acid Chemical compound NCP(O)(O)=O MGRVRXRGTBOSHW-UHFFFAOYSA-N 0.000 description 2
- JDZOTSLZMQDFLG-BTJKTKAUSA-N (z)-but-2-enedioic acid;2-(2,2-dicyclohexylethyl)piperidine Chemical compound OC(=O)\C=C/C(O)=O.C1CCCNC1CC(C1CCCCC1)C1CCCCC1 JDZOTSLZMQDFLG-BTJKTKAUSA-N 0.000 description 2
- VILCJCGEZXAXTO-UHFFFAOYSA-N 2,2,2-tetramine Chemical compound NCCNCCNCCN VILCJCGEZXAXTO-UHFFFAOYSA-N 0.000 description 2
- TXQPXJKRNHJWAX-UHFFFAOYSA-N 2-(3-aminopropylamino)ethylsulfanylphosphonic acid;trihydrate Chemical compound O.O.O.NCCCNCCSP(O)(O)=O TXQPXJKRNHJWAX-UHFFFAOYSA-N 0.000 description 2
- MSWZFWKMSRAUBD-UHFFFAOYSA-N 2-Amino-2-Deoxy-Hexose Chemical compound NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 2
- PTKSEFOSCHHMPD-SNVBAGLBSA-N 2-amino-n-[(2s)-2-(2,5-dimethoxyphenyl)-2-hydroxyethyl]acetamide Chemical compound COC1=CC=C(OC)C([C@H](O)CNC(=O)CN)=C1 PTKSEFOSCHHMPD-SNVBAGLBSA-N 0.000 description 2
- ISPYQTSUDJAMAB-UHFFFAOYSA-N 2-chlorophenol Chemical compound OC1=CC=CC=C1Cl ISPYQTSUDJAMAB-UHFFFAOYSA-N 0.000 description 2
- PUYOAVGNCWPANW-UHFFFAOYSA-N 2-methylpropyl 4-aminobenzoate Chemical compound CC(C)COC(=O)C1=CC=C(N)C=C1 PUYOAVGNCWPANW-UHFFFAOYSA-N 0.000 description 2
- SLAMLWHELXOEJZ-UHFFFAOYSA-N 2-nitrobenzoic acid Chemical compound OC(=O)C1=CC=CC=C1[N+]([O-])=O SLAMLWHELXOEJZ-UHFFFAOYSA-N 0.000 description 2
- AOJJSUZBOXZQNB-VTZDEGQISA-N 4'-epidoxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-VTZDEGQISA-N 0.000 description 2
- VTMJKPGFERYGJF-UHFFFAOYSA-N 4-Carboxyphenylglycine Chemical compound OC(=O)C(N)C1=CC=C(C(O)=O)C=C1 VTMJKPGFERYGJF-UHFFFAOYSA-N 0.000 description 2
- RZTAMFZIAATZDJ-HNNXBMFYSA-N 5-o-ethyl 3-o-methyl (4s)-4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound CCOC(=O)C1=C(C)NC(C)=C(C(=O)OC)[C@@H]1C1=CC=CC(Cl)=C1Cl RZTAMFZIAATZDJ-HNNXBMFYSA-N 0.000 description 2
- BKYKPTRYDKTTJY-UHFFFAOYSA-N 6-chloro-3-(cyclopentylmethyl)-1,1-dioxo-3,4-dihydro-2H-1$l^{6},2,4-benzothiadiazine-7-sulfonamide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(S(N2)(=O)=O)=C1NC2CC1CCCC1 BKYKPTRYDKTTJY-UHFFFAOYSA-N 0.000 description 2
- VDOSWXIDETXFET-UHFFFAOYSA-N Afloqualone Chemical compound CC1=CC=CC=C1N1C(=O)C2=CC(N)=CC=C2N=C1CF VDOSWXIDETXFET-UHFFFAOYSA-N 0.000 description 2
- WKEMJKQOLOHJLZ-UHFFFAOYSA-N Almogran Chemical compound C1=C2C(CCN(C)C)=CNC2=CC=C1CS(=O)(=O)N1CCCC1 WKEMJKQOLOHJLZ-UHFFFAOYSA-N 0.000 description 2
- OVCDSSHSILBFBN-UHFFFAOYSA-N Amodiaquine Chemical compound C1=C(O)C(CN(CC)CC)=CC(NC=2C3=CC=C(Cl)C=C3N=CC=2)=C1 OVCDSSHSILBFBN-UHFFFAOYSA-N 0.000 description 2
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- 239000004475 Arginine Substances 0.000 description 2
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 2
- XPCFTKFZXHTYIP-PMACEKPBSA-N Benazepril Chemical compound C([C@@H](C(=O)OCC)N[C@@H]1C(N(CC(O)=O)C2=CC=CC=C2CC1)=O)CC1=CC=CC=C1 XPCFTKFZXHTYIP-PMACEKPBSA-N 0.000 description 2
- 239000004072 C09CA03 - Valsartan Substances 0.000 description 2
- 239000002053 C09CA06 - Candesartan Substances 0.000 description 2
- KORNTPPJEAJQIU-KJXAQDMKSA-N Cabaser Chemical compound C1=CC([C@H]2C[C@H](CN(CC=C)[C@@H]2C2)C(=O)N(CCCN(C)C)C(=O)NCC)=C3C2=CNC3=C1 KORNTPPJEAJQIU-KJXAQDMKSA-N 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical group [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- 229930186147 Cephalosporin Natural products 0.000 description 2
- JZUFKLXOESDKRF-UHFFFAOYSA-N Chlorothiazide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NCNS2(=O)=O JZUFKLXOESDKRF-UHFFFAOYSA-N 0.000 description 2
- VWFCHDSQECPREK-LURJTMIESA-N Cidofovir Chemical compound NC=1C=CN(C[C@@H](CO)OCP(O)(O)=O)C(=O)N=1 VWFCHDSQECPREK-LURJTMIESA-N 0.000 description 2
- GJSURZIOUXUGAL-UHFFFAOYSA-N Clonidine Chemical compound ClC1=CC=CC(Cl)=C1NC1=NCCN1 GJSURZIOUXUGAL-UHFFFAOYSA-N 0.000 description 2
- 229920002911 Colestipol Polymers 0.000 description 2
- UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 description 2
- DYDCUQKUCUHJBH-UWTATZPHSA-N D-Cycloserine Chemical compound N[C@@H]1CONC1=O DYDCUQKUCUHJBH-UWTATZPHSA-N 0.000 description 2
- 206010012289 Dementia Diseases 0.000 description 2
- XQSPYNMVSIKCOC-NTSWFWBYSA-N Emtricitabine Chemical compound C1=C(F)C(N)=NC(=O)N1[C@H]1O[C@@H](CO)SC1 XQSPYNMVSIKCOC-NTSWFWBYSA-N 0.000 description 2
- 108010061435 Enalapril Proteins 0.000 description 2
- HTIJFSOGRVMCQR-UHFFFAOYSA-N Epirubicin Natural products COc1cccc2C(=O)c3c(O)c4CC(O)(CC(OC5CC(N)C(=O)C(C)O5)c4c(O)c3C(=O)c12)C(=O)CO HTIJFSOGRVMCQR-UHFFFAOYSA-N 0.000 description 2
- CNBHDDBNEKKMJH-ZFWWWQNUSA-N Eseridine Chemical compound O1N(C)CC[C@@]2(C)C3=CC(OC(=O)NC)=CC=C3N(C)[C@H]21 CNBHDDBNEKKMJH-ZFWWWQNUSA-N 0.000 description 2
- 102100039250 Essential MCU regulator, mitochondrial Human genes 0.000 description 2
- 108010086677 Gonadotropins Proteins 0.000 description 2
- 102000006771 Gonadotropins Human genes 0.000 description 2
- 101000813097 Homo sapiens Essential MCU regulator, mitochondrial Proteins 0.000 description 2
- IRJCBFDCFXCWGO-UHFFFAOYSA-N Ibotenic acid Natural products OC(=O)C(N)C1=CC(=O)NO1 IRJCBFDCFXCWGO-UHFFFAOYSA-N 0.000 description 2
- XDXDZDZNSLXDNA-TZNDIEGXSA-N Idarubicin Chemical compound C1[C@H](N)[C@H](O)[C@H](C)O[C@H]1O[C@@H]1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2C[C@@](O)(C(C)=O)C1 XDXDZDZNSLXDNA-TZNDIEGXSA-N 0.000 description 2
- XDXDZDZNSLXDNA-UHFFFAOYSA-N Idarubicin Natural products C1C(N)C(O)C(C)OC1OC1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2CC(O)(C(C)=O)C1 XDXDZDZNSLXDNA-UHFFFAOYSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical group C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- JUZNIMUFDBIJCM-ANEDZVCMSA-N Invanz Chemical compound O=C([C@H]1NC[C@H](C1)SC=1[C@H](C)[C@@H]2[C@H](C(N2C=1C(O)=O)=O)[C@H](O)C)NC1=CC=CC(C(O)=O)=C1 JUZNIMUFDBIJCM-ANEDZVCMSA-N 0.000 description 2
- OIRFJRBSRORBCM-UHFFFAOYSA-N Iopanoic acid Chemical compound CCC(C(O)=O)CC1=C(I)C=C(I)C(N)=C1I OIRFJRBSRORBCM-UHFFFAOYSA-N 0.000 description 2
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 2
- WXFIGDLSSYIKKV-RCOVLWMOSA-N L-Metaraminol Chemical compound C[C@H](N)[C@H](O)C1=CC=CC(O)=C1 WXFIGDLSSYIKKV-RCOVLWMOSA-N 0.000 description 2
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 2
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 2
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 2
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 2
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 2
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 2
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 2
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 2
- XUIIKFGFIJCVMT-LBPRGKRZSA-N L-thyroxine Chemical compound IC1=CC(C[C@H]([NH3+])C([O-])=O)=CC(I)=C1OC1=CC(I)=C(O)C(I)=C1 XUIIKFGFIJCVMT-LBPRGKRZSA-N 0.000 description 2
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 2
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 2
- NHTGHBARYWONDQ-JTQLQIEISA-N L-α-methyl-Tyrosine Chemical compound OC(=O)[C@](N)(C)CC1=CC=C(O)C=C1 NHTGHBARYWONDQ-JTQLQIEISA-N 0.000 description 2
- 239000005517 L01XE01 - Imatinib Substances 0.000 description 2
- 239000005411 L01XE02 - Gefitinib Substances 0.000 description 2
- 239000005551 L01XE03 - Erlotinib Substances 0.000 description 2
- 240000008415 Lactuca sativa Species 0.000 description 2
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 2
- 108010007859 Lisinopril Proteins 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- JUOSGGQXEBBCJB-UHFFFAOYSA-N Metanicotine Natural products CNCCC=CC1=CC=CN=C1 JUOSGGQXEBBCJB-UHFFFAOYSA-N 0.000 description 2
- WJAJPNHVVFWKKL-UHFFFAOYSA-N Methoxamine Chemical group COC1=CC=C(OC)C(C(O)C(C)N)=C1 WJAJPNHVVFWKKL-UHFFFAOYSA-N 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- DUGOZIWVEXMGBE-UHFFFAOYSA-N Methylphenidate Chemical compound C=1C=CC=CC=1C(C(=O)OC)C1CCCCN1 DUGOZIWVEXMGBE-UHFFFAOYSA-N 0.000 description 2
- UWWDHYUMIORJTA-HSQYWUDLSA-N Moexipril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](CC2=CC(OC)=C(OC)C=C2C1)C(O)=O)CC1=CC=CC=C1 UWWDHYUMIORJTA-HSQYWUDLSA-N 0.000 description 2
- HSMNQINEKMPTIC-UHFFFAOYSA-N N-(4-aminobenzoyl)glycine Chemical compound NC1=CC=C(C(=O)NCC(O)=O)C=C1 HSMNQINEKMPTIC-UHFFFAOYSA-N 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- HOKKHZGPKSLGJE-GSVOUGTGSA-N N-Methyl-D-aspartic acid Chemical compound CN[C@@H](C(O)=O)CC(O)=O HOKKHZGPKSLGJE-GSVOUGTGSA-N 0.000 description 2
- XUYPXLNMDZIRQH-LURJTMIESA-N N-acetyl-L-methionine Chemical compound CSCC[C@@H](C(O)=O)NC(C)=O XUYPXLNMDZIRQH-LURJTMIESA-N 0.000 description 2
- UBQYURCVBFRUQT-UHFFFAOYSA-N N-benzoyl-Ferrioxamine B Chemical compound CC(=O)N(O)CCCCCNC(=O)CCC(=O)N(O)CCCCCNC(=O)CCC(=O)N(O)CCCCCN UBQYURCVBFRUQT-UHFFFAOYSA-N 0.000 description 2
- GIYXAJPCNFJEHY-UHFFFAOYSA-N N-methyl-3-phenyl-3-[4-(trifluoromethyl)phenoxy]-1-propanamine hydrochloride (1:1) Chemical compound Cl.C=1C=CC=CC=1C(CCNC)OC1=CC=C(C(F)(F)F)C=C1 GIYXAJPCNFJEHY-UHFFFAOYSA-N 0.000 description 2
- VTJITQLWKYPNTF-UHFFFAOYSA-N N1=NC=CC=C1.S1C=CC=C1.ClC1=CC=CC=C1 Chemical compound N1=NC=CC=C1.S1C=CC=C1.ClC1=CC=CC=C1 VTJITQLWKYPNTF-UHFFFAOYSA-N 0.000 description 2
- ZBBHBTPTTSWHBA-UHFFFAOYSA-N Nicardipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OCCN(C)CC=2C=CC=CC=2)C1C1=CC=CC([N+]([O-])=O)=C1 ZBBHBTPTTSWHBA-UHFFFAOYSA-N 0.000 description 2
- RSPISYXLHRIGJD-UHFFFAOYSA-N OOOO Chemical compound OOOO RSPISYXLHRIGJD-UHFFFAOYSA-N 0.000 description 2
- KUGRPPRAQNPSQD-UHFFFAOYSA-N OOOOO Chemical compound OOOOO KUGRPPRAQNPSQD-UHFFFAOYSA-N 0.000 description 2
- 239000005480 Olmesartan Substances 0.000 description 2
- IQPSEEYGBUAQFF-UHFFFAOYSA-N Pantoprazole Chemical compound COC1=CC=NC(CS(=O)C=2NC3=CC=C(OC(F)F)C=C3N=2)=C1OC IQPSEEYGBUAQFF-UHFFFAOYSA-N 0.000 description 2
- JNTOCHDNEULJHD-UHFFFAOYSA-N Penciclovir Chemical compound N1C(N)=NC(=O)C2=C1N(CCC(CO)CO)C=N2 JNTOCHDNEULJHD-UHFFFAOYSA-N 0.000 description 2
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 2
- 241000219780 Pueraria Species 0.000 description 2
- QSMYZGMJSGUWPM-UHFFFAOYSA-N RS 39604 hydrochloride Chemical compound Cl.COC1=CC(OC)=CC(COC=2C(=CC(Cl)=C(N)C=2)C(=O)CCC2CCN(CCNS(C)(=O)=O)CC2)=C1 QSMYZGMJSGUWPM-UHFFFAOYSA-N 0.000 description 2
- URWAJWIAIPFPJE-UHFFFAOYSA-N Rickamicin Natural products O1CC(O)(C)C(NC)C(O)C1OC1C(O)C(OC2C(CC=C(CN)O2)N)C(N)CC1N URWAJWIAIPFPJE-UHFFFAOYSA-N 0.000 description 2
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 2
- 229930192786 Sisomicin Natural products 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- QKLSCPPJEVXONT-UHFFFAOYSA-N Sulfametomidine Chemical compound CC1=NC(OC)=CC(NS(=O)(=O)C=2C=CC(N)=CC=2)=N1 QKLSCPPJEVXONT-UHFFFAOYSA-N 0.000 description 2
- PJSFRIWCGOHTNF-UHFFFAOYSA-N Sulphormetoxin Chemical compound COC1=NC=NC(NS(=O)(=O)C=2C=CC(N)=CC=2)=C1OC PJSFRIWCGOHTNF-UHFFFAOYSA-N 0.000 description 2
- DRHKJLXJIQTDTD-OAHLLOKOSA-N Tamsulosine Chemical compound CCOC1=CC=CC=C1OCCN[C@H](C)CC1=CC=C(OC)C(S(N)(=O)=O)=C1 DRHKJLXJIQTDTD-OAHLLOKOSA-N 0.000 description 2
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 2
- 239000004473 Threonine Substances 0.000 description 2
- NGBFQHCMQULJNZ-UHFFFAOYSA-N Torsemide Chemical compound CC(C)NC(=O)NS(=O)(=O)C1=CN=CC=C1NC1=CC=CC(C)=C1 NGBFQHCMQULJNZ-UHFFFAOYSA-N 0.000 description 2
- 241000209140 Triticum Species 0.000 description 2
- 235000021307 Triticum Nutrition 0.000 description 2
- YSIITVVESCNIPR-UHFFFAOYSA-N Troxipide Chemical compound COC1=C(OC)C(OC)=CC(C(=O)NC2CNCCC2)=C1 YSIITVVESCNIPR-UHFFFAOYSA-N 0.000 description 2
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 2
- 239000006035 Tryptophane Substances 0.000 description 2
- WPVFJKSGQUFQAP-GKAPJAKFSA-N Valcyte Chemical compound N1C(N)=NC(=O)C2=C1N(COC(CO)COC(=O)[C@@H](N)C(C)C)C=N2 WPVFJKSGQUFQAP-GKAPJAKFSA-N 0.000 description 2
- SECKRCOLJRRGGV-UHFFFAOYSA-N Vardenafil Chemical compound CCCC1=NC(C)=C(C(N=2)=O)N1NC=2C(C(=CC=1)OCC)=CC=1S(=O)(=O)N1CCN(CC)CC1 SECKRCOLJRRGGV-UHFFFAOYSA-N 0.000 description 2
- 201000004810 Vascular dementia Diseases 0.000 description 2
- 241000405119 Virga Species 0.000 description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
- 229960001997 adefovir Drugs 0.000 description 2
- 229950009353 afloqualone Drugs 0.000 description 2
- QYPPJABKJHAVHS-UHFFFAOYSA-N agmatine Chemical compound NCCCCNC(N)=N QYPPJABKJHAVHS-UHFFFAOYSA-N 0.000 description 2
- UUZPPAMZDFLUHD-VUJLHGSVSA-N alatrofloxacin Chemical compound C([C@@H]1[C@H]([C@@H]1C1)NC(=O)[C@H](C)NC(=O)[C@@H](N)C)N1C(C(=CC=1C(=O)C(C(O)=O)=C2)F)=NC=1N2C1=CC=C(F)C=C1F UUZPPAMZDFLUHD-VUJLHGSVSA-N 0.000 description 2
- 229960000919 alatrofloxacin Drugs 0.000 description 2
- 229940062527 alendronate Drugs 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 229960002133 almotriptan Drugs 0.000 description 2
- JSWZEAMFRNKZNL-UHFFFAOYSA-N alosetron Chemical compound N1C=NC(CN2C(C3=C(N(C4=CC=CC=C43)C)CC2)=O)=C1C JSWZEAMFRNKZNL-UHFFFAOYSA-N 0.000 description 2
- 229960001097 amifostine Drugs 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- ROBVIMPUHSLWNV-UHFFFAOYSA-N aminoglutethimide Chemical compound C=1C=C(N)C=CC=1C1(CC)CCC(=O)NC1=O ROBVIMPUHSLWNV-UHFFFAOYSA-N 0.000 description 2
- 229960003437 aminoglutethimide Drugs 0.000 description 2
- 229960004567 aminohippuric acid Drugs 0.000 description 2
- SGRYPYWGNKJSDL-UHFFFAOYSA-N amlexanox Chemical compound NC1=C(C(O)=O)C=C2C(=O)C3=CC(C(C)C)=CC=C3OC2=N1 SGRYPYWGNKJSDL-UHFFFAOYSA-N 0.000 description 2
- 229960003731 amlexanox Drugs 0.000 description 2
- 229960001444 amodiaquine Drugs 0.000 description 2
- YMARZQAQMVYCKC-OEMFJLHTSA-N amprenavir Chemical compound C([C@@H]([C@H](O)CN(CC(C)C)S(=O)(=O)C=1C=CC(N)=CC=1)NC(=O)O[C@@H]1COCC1)C1=CC=CC=C1 YMARZQAQMVYCKC-OEMFJLHTSA-N 0.000 description 2
- 229960001830 amprenavir Drugs 0.000 description 2
- RNLQIBCLLYYYFJ-UHFFFAOYSA-N amrinone Chemical compound N1C(=O)C(N)=CC(C=2C=CN=CC=2)=C1 RNLQIBCLLYYYFJ-UHFFFAOYSA-N 0.000 description 2
- 229960002105 amrinone Drugs 0.000 description 2
- XCPGHVQEEXUHNC-UHFFFAOYSA-N amsacrine Chemical compound COC1=CC(NS(C)(=O)=O)=CC=C1NC1=C(C=CC=C2)C2=NC2=CC=CC=C12 XCPGHVQEEXUHNC-UHFFFAOYSA-N 0.000 description 2
- 229960001220 amsacrine Drugs 0.000 description 2
- OTBXOEAOVRKTNQ-UHFFFAOYSA-N anagrelide Chemical compound N1=C2NC(=O)CN2CC2=C(Cl)C(Cl)=CC=C21 OTBXOEAOVRKTNQ-UHFFFAOYSA-N 0.000 description 2
- 229960001694 anagrelide Drugs 0.000 description 2
- 230000036506 anxiety Effects 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- KXNPVXPOPUZYGB-XYVMCAHJSA-N argatroban Chemical compound OC(=O)[C@H]1C[C@H](C)CCN1C(=O)[C@H](CCCN=C(N)N)NS(=O)(=O)C1=CC=CC2=C1NC[C@H](C)C2 KXNPVXPOPUZYGB-XYVMCAHJSA-N 0.000 description 2
- 229960003856 argatroban Drugs 0.000 description 2
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 2
- 229960001230 asparagine Drugs 0.000 description 2
- 235000009582 asparagine Nutrition 0.000 description 2
- KUCQYCKVKVOKAY-CTYIDZIISA-N atovaquone Chemical compound C1([C@H]2CC[C@@H](CC2)C2=C(C(C3=CC=CC=C3C2=O)=O)O)=CC=C(Cl)C=C1 KUCQYCKVKVOKAY-CTYIDZIISA-N 0.000 description 2
- 229960003159 atovaquone Drugs 0.000 description 2
- 239000012752 auxiliary agent Substances 0.000 description 2
- 229960004530 benazepril Drugs 0.000 description 2
- 229960005274 benzocaine Drugs 0.000 description 2
- 229960001303 benzoctamine Drugs 0.000 description 2
- GNRXCIONJWKSEA-UHFFFAOYSA-N benzoctamine Chemical compound C12=CC=CC=C2C2(CNC)C3=CC=CC=C3C1CC2 GNRXCIONJWKSEA-UHFFFAOYSA-N 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 210000004204 blood vessel Anatomy 0.000 description 2
- ZBPLOVFIXSTCRZ-UHFFFAOYSA-N bromfenac Chemical compound NC1=C(CC(O)=O)C=CC=C1C(=O)C1=CC=C(Br)C=C1 ZBPLOVFIXSTCRZ-UHFFFAOYSA-N 0.000 description 2
- 229960003655 bromfenac Drugs 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 229960004064 bumetanide Drugs 0.000 description 2
- MAEIEVLCKWDQJH-UHFFFAOYSA-N bumetanide Chemical compound CCCCNC1=CC(C(O)=O)=CC(S(N)(=O)=O)=C1OC1=CC=CC=C1 MAEIEVLCKWDQJH-UHFFFAOYSA-N 0.000 description 2
- 229960001058 bupropion Drugs 0.000 description 2
- SNPPWIUOZRMYNY-UHFFFAOYSA-N bupropion Chemical compound CC(C)(C)NC(C)C(=O)C1=CC=CC(Cl)=C1 SNPPWIUOZRMYNY-UHFFFAOYSA-N 0.000 description 2
- HGBFRHCDYZJRAO-UHFFFAOYSA-N butizide Chemical compound ClC1=C(S(N)(=O)=O)C=C2S(=O)(=O)NC(CC(C)C)NC2=C1 HGBFRHCDYZJRAO-UHFFFAOYSA-N 0.000 description 2
- 229950008955 butizide Drugs 0.000 description 2
- 229960004596 cabergoline Drugs 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 229960000932 candesartan Drugs 0.000 description 2
- SGZAIDDFHDDFJU-UHFFFAOYSA-N candesartan Chemical compound CCOC1=NC2=CC=CC(C(O)=O)=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1C1=NN=N[N]1 SGZAIDDFHDDFJU-UHFFFAOYSA-N 0.000 description 2
- 229960004205 carbidopa Drugs 0.000 description 2
- TZFNLOMSOLWIDK-JTQLQIEISA-N carbidopa (anhydrous) Chemical compound NN[C@@](C(O)=O)(C)CC1=CC=C(O)C(O)=C1 TZFNLOMSOLWIDK-JTQLQIEISA-N 0.000 description 2
- 125000002837 carbocyclic group Chemical group 0.000 description 2
- VDTNNGKXZGSZIP-UHFFFAOYSA-N carbutamide Chemical compound CCCCNC(=O)NS(=O)(=O)C1=CC=C(N)C=C1 VDTNNGKXZGSZIP-UHFFFAOYSA-N 0.000 description 2
- 229960003362 carbutamide Drugs 0.000 description 2
- 239000012876 carrier material Substances 0.000 description 2
- NPAKNKYSJIDKMW-UHFFFAOYSA-N carvedilol Chemical compound COC1=CC=CC=C1OCCNCC(O)COC1=CC=CC2=NC3=CC=C[CH]C3=C12 NPAKNKYSJIDKMW-UHFFFAOYSA-N 0.000 description 2
- 229960004195 carvedilol Drugs 0.000 description 2
- 238000006555 catalytic reaction Methods 0.000 description 2
- QYIYFLOTGYLRGG-GPCCPHFNSA-N cefaclor Chemical compound C1([C@H](C(=O)N[C@@H]2C(N3C(=C(Cl)CS[C@@H]32)C(O)=O)=O)N)=CC=CC=C1 QYIYFLOTGYLRGG-GPCCPHFNSA-N 0.000 description 2
- 229960005361 cefaclor Drugs 0.000 description 2
- 229960002142 cefditoren pivoxil Drugs 0.000 description 2
- 229960002588 cefradine Drugs 0.000 description 2
- RDMOROXKXONCAL-UEKVPHQBSA-N cefroxadine Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@@H]3N(C2=O)C(=C(CS3)OC)C(O)=O)=CCC=CC1 RDMOROXKXONCAL-UEKVPHQBSA-N 0.000 description 2
- 229960003844 cefroxadine Drugs 0.000 description 2
- 230000010261 cell growth Effects 0.000 description 2
- 229940083181 centrally acting adntiadrenergic agent methyldopa Drugs 0.000 description 2
- 229940124587 cephalosporin Drugs 0.000 description 2
- RDLPVSKMFDYCOR-UEKVPHQBSA-N cephradine Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@@H]3N(C2=O)C(=C(CS3)C)C(O)=O)=CCC=CC1 RDLPVSKMFDYCOR-UEKVPHQBSA-N 0.000 description 2
- UKTAZPQNNNJVKR-KJGYPYNMSA-N chembl2368925 Chemical compound C1=CC=C2C(C(O[C@@H]3C[C@@H]4C[C@H]5C[C@@H](N4CC5=O)C3)=O)=CNC2=C1 UKTAZPQNNNJVKR-KJGYPYNMSA-N 0.000 description 2
- 229960004782 chlordiazepoxide Drugs 0.000 description 2
- ANTSCNMPPGJYLG-UHFFFAOYSA-N chlordiazepoxide Chemical compound O=N=1CC(NC)=NC2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 ANTSCNMPPGJYLG-UHFFFAOYSA-N 0.000 description 2
- DDKMFOUTRRODRE-UHFFFAOYSA-N chloromethanone Chemical compound Cl[C]=O DDKMFOUTRRODRE-UHFFFAOYSA-N 0.000 description 2
- VDANGULDQQJODZ-UHFFFAOYSA-N chloroprocaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1Cl VDANGULDQQJODZ-UHFFFAOYSA-N 0.000 description 2
- 229960002023 chloroprocaine Drugs 0.000 description 2
- 229960000724 cidofovir Drugs 0.000 description 2
- VDHAWDNDOKGFTD-MRXNPFEDSA-N cinacalcet Chemical compound N([C@H](C)C=1C2=CC=CC=C2C=CC=1)CCCC1=CC=CC(C(F)(F)F)=C1 VDHAWDNDOKGFTD-MRXNPFEDSA-N 0.000 description 2
- 229960003315 cinacalcet Drugs 0.000 description 2
- 229960005132 cisapride Drugs 0.000 description 2
- DCSUBABJRXZOMT-IRLDBZIGSA-N cisapride Chemical compound C([C@@H]([C@@H](CC1)NC(=O)C=2C(=CC(N)=C(Cl)C=2)OC)OC)N1CCCOC1=CC=C(F)C=C1 DCSUBABJRXZOMT-IRLDBZIGSA-N 0.000 description 2
- DCSUBABJRXZOMT-UHFFFAOYSA-N cisapride Natural products C1CC(NC(=O)C=2C(=CC(N)=C(Cl)C=2)OC)C(OC)CN1CCCOC1=CC=C(F)C=C1 DCSUBABJRXZOMT-UHFFFAOYSA-N 0.000 description 2
- WDDPHFBMKLOVOX-AYQXTPAHSA-N clofarabine Chemical compound C1=NC=2C(N)=NC(Cl)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@@H]1F WDDPHFBMKLOVOX-AYQXTPAHSA-N 0.000 description 2
- 229960000928 clofarabine Drugs 0.000 description 2
- 229950000649 clortermine Drugs 0.000 description 2
- HXCXASJHZQXCKK-UHFFFAOYSA-N clortermine Chemical compound CC(C)(N)CC1=CC=CC=C1Cl HXCXASJHZQXCKK-UHFFFAOYSA-N 0.000 description 2
- GMRWGQCZJGVHKL-UHFFFAOYSA-N colestipol Chemical compound ClCC1CO1.NCCNCCNCCNCCN GMRWGQCZJGVHKL-UHFFFAOYSA-N 0.000 description 2
- 229960002604 colestipol Drugs 0.000 description 2
- 229960000562 conivaptan Drugs 0.000 description 2
- JGBBVDFNZSRLIF-UHFFFAOYSA-N conivaptan Chemical compound C12=CC=CC=C2C=2[N]C(C)=NC=2CCN1C(=O)C(C=C1)=CC=C1NC(=O)C1=CC=CC=C1C1=CC=CC=C1 JGBBVDFNZSRLIF-UHFFFAOYSA-N 0.000 description 2
- 229960004244 cyclacillin Drugs 0.000 description 2
- HGBLNBBNRORJKI-WCABBAIRSA-N cyclacillin Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)C1(N)CCCCC1 HGBLNBBNRORJKI-WCABBAIRSA-N 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- 229960003206 cyclopenthiazide Drugs 0.000 description 2
- UFULAYFCSOUIOV-UHFFFAOYSA-N cysteamine Chemical compound NCCS UFULAYFCSOUIOV-UHFFFAOYSA-N 0.000 description 2
- KWGRBVOPPLSCSI-UHFFFAOYSA-N d-ephedrine Natural products CNC(C)C(O)C1=CC=CC=C1 KWGRBVOPPLSCSI-UHFFFAOYSA-N 0.000 description 2
- 230000002354 daily effect Effects 0.000 description 2
- 229960000958 deferoxamine Drugs 0.000 description 2
- 229960005319 delavirdine Drugs 0.000 description 2
- 230000002939 deleterious effect Effects 0.000 description 2
- 229960004253 dexmedetomidine Drugs 0.000 description 2
- HRLIOXLXPOHXTA-NSHDSACASA-N dexmedetomidine Chemical compound C1([C@@H](C)C=2C(=C(C)C=CC=2)C)=CN=C[N]1 HRLIOXLXPOHXTA-NSHDSACASA-N 0.000 description 2
- VTMVHDZWSFQSQP-VBNZEHGJSA-N dezocine Chemical compound C1CCCC[C@H]2CC3=CC=C(O)C=C3[C@]1(C)[C@H]2N VTMVHDZWSFQSQP-VBNZEHGJSA-N 0.000 description 2
- DCOPUUMXTXDBNB-UHFFFAOYSA-N diclofenac Chemical compound OC(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl DCOPUUMXTXDBNB-UHFFFAOYSA-N 0.000 description 2
- 229960001259 diclofenac Drugs 0.000 description 2
- NYDXNILOWQXUOF-UHFFFAOYSA-L disodium;2-[[4-[2-(2-amino-4-oxo-1,7-dihydropyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]amino]pentanedioate Chemical compound [Na+].[Na+].C=1NC=2NC(N)=NC(=O)C=2C=1CCC1=CC=C(C(=O)NC(CCC([O-])=O)C([O-])=O)C=C1 NYDXNILOWQXUOF-UHFFFAOYSA-L 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- DLNKOYKMWOXYQA-UHFFFAOYSA-N dl-pseudophenylpropanolamine Natural products CC(N)C(O)C1=CC=CC=C1 DLNKOYKMWOXYQA-UHFFFAOYSA-N 0.000 description 2
- 229960003413 dolasetron Drugs 0.000 description 2
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 2
- RUZYUOTYCVRMRZ-UHFFFAOYSA-N doxazosin Chemical compound C1OC2=CC=CC=C2OC1C(=O)N(CC1)CCN1C1=NC(N)=C(C=C(C(OC)=C2)OC)C2=N1 RUZYUOTYCVRMRZ-UHFFFAOYSA-N 0.000 description 2
- 229960001389 doxazosin Drugs 0.000 description 2
- 230000002526 effect on cardiovascular system Effects 0.000 description 2
- 229960002759 eflornithine Drugs 0.000 description 2
- VLCYCQAOQCDTCN-UHFFFAOYSA-N eflornithine Chemical compound NCCCC(N)(C(F)F)C(O)=O VLCYCQAOQCDTCN-UHFFFAOYSA-N 0.000 description 2
- BSPSXMXQKZZNFP-UHFFFAOYSA-N elfazepam Chemical compound N=1CC(=O)N(CCS(=O)(=O)CC)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1F BSPSXMXQKZZNFP-UHFFFAOYSA-N 0.000 description 2
- 229950008850 elfazepam Drugs 0.000 description 2
- 229960000366 emtricitabine Drugs 0.000 description 2
- 229960000873 enalapril Drugs 0.000 description 2
- GBXSMTUPTTWBMN-XIRDDKMYSA-N enalapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(O)=O)CC1=CC=CC=C1 GBXSMTUPTTWBMN-XIRDDKMYSA-N 0.000 description 2
- 229960002549 enoxacin Drugs 0.000 description 2
- IDYZIJYBMGIQMJ-UHFFFAOYSA-N enoxacin Chemical compound N1=C2N(CC)C=C(C(O)=O)C(=O)C2=CC(F)=C1N1CCNCC1 IDYZIJYBMGIQMJ-UHFFFAOYSA-N 0.000 description 2
- WHWZLSFABNNENI-UHFFFAOYSA-N epinastine Chemical compound C1C2=CC=CC=C2C2CN=C(N)N2C2=CC=CC=C21 WHWZLSFABNNENI-UHFFFAOYSA-N 0.000 description 2
- 229960003449 epinastine Drugs 0.000 description 2
- 229960001904 epirubicin Drugs 0.000 description 2
- 210000000981 epithelium Anatomy 0.000 description 2
- AAKJLRGGTJKAMG-UHFFFAOYSA-N erlotinib Chemical compound C=12C=C(OCCOC)C(OCCOC)=CC2=NC=NC=1NC1=CC=CC(C#C)=C1 AAKJLRGGTJKAMG-UHFFFAOYSA-N 0.000 description 2
- 229960001433 erlotinib Drugs 0.000 description 2
- 229960002770 ertapenem Drugs 0.000 description 2
- 229950003340 eseridine Drugs 0.000 description 2
- AUAHHJJRFHRVPV-BZDVOYDHSA-N ethambutol dihydrochloride Chemical compound [Cl-].[Cl-].CC[C@@H](CO)[NH2+]CC[NH2+][C@@H](CC)CO AUAHHJJRFHRVPV-BZDVOYDHSA-N 0.000 description 2
- 235000019441 ethanol Nutrition 0.000 description 2
- 229960005293 etodolac Drugs 0.000 description 2
- 239000003257 excitatory amino acid Substances 0.000 description 2
- 230000002461 excitatory amino acid Effects 0.000 description 2
- 229960004396 famciclovir Drugs 0.000 description 2
- GGXKWVWZWMLJEH-UHFFFAOYSA-N famcyclovir Chemical compound N1=C(N)N=C2N(CCC(COC(=O)C)COC(C)=O)C=NC2=C1 GGXKWVWZWMLJEH-UHFFFAOYSA-N 0.000 description 2
- XUFQPHANEAPEMJ-UHFFFAOYSA-N famotidine Chemical compound NC(N)=NC1=NC(CSCCC(N)=NS(N)(=O)=O)=CS1 XUFQPHANEAPEMJ-UHFFFAOYSA-N 0.000 description 2
- 229960001596 famotidine Drugs 0.000 description 2
- 230000002349 favourable effect Effects 0.000 description 2
- 229960003580 felodipine Drugs 0.000 description 2
- 229960002724 fenoldopam Drugs 0.000 description 2
- TVURRHSHRRELCG-UHFFFAOYSA-N fenoldopam Chemical compound C1=CC(O)=CC=C1C1C2=CC(O)=C(O)C(Cl)=C2CCNC1 TVURRHSHRRELCG-UHFFFAOYSA-N 0.000 description 2
- XRECTZIEBJDKEO-UHFFFAOYSA-N flucytosine Chemical compound NC1=NC(=O)NC=C1F XRECTZIEBJDKEO-UHFFFAOYSA-N 0.000 description 2
- 229960004413 flucytosine Drugs 0.000 description 2
- LPEPZBJOKDYZAD-UHFFFAOYSA-N flufenamic acid Chemical compound OC(=O)C1=CC=CC=C1NC1=CC=CC(C(F)(F)F)=C1 LPEPZBJOKDYZAD-UHFFFAOYSA-N 0.000 description 2
- 229960000389 fluoxetine hydrochloride Drugs 0.000 description 2
- 229960004285 fomepizole Drugs 0.000 description 2
- WXXNSDVNQFRQIA-UHFFFAOYSA-N fomepizole Chemical compound CC1=CN=N[CH]1 WXXNSDVNQFRQIA-UHFFFAOYSA-N 0.000 description 2
- MLBVMOWEQCZNCC-OEMFJLHTSA-N fosamprenavir Chemical compound C([C@@H]([C@H](OP(O)(O)=O)CN(CC(C)C)S(=O)(=O)C=1C=CC(N)=CC=1)NC(=O)O[C@@H]1COCC1)C1=CC=CC=C1 MLBVMOWEQCZNCC-OEMFJLHTSA-N 0.000 description 2
- 229960003142 fosamprenavir Drugs 0.000 description 2
- 229960002284 frovatriptan Drugs 0.000 description 2
- SIBNYOSJIXCDRI-SECBINFHSA-N frovatriptan Chemical compound C1=C(C(N)=O)[CH]C2=C(C[C@H](NC)CC3)C3=NC2=C1 SIBNYOSJIXCDRI-SECBINFHSA-N 0.000 description 2
- 229960003883 furosemide Drugs 0.000 description 2
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 2
- 125000002541 furyl group Chemical group 0.000 description 2
- 229960002963 ganciclovir Drugs 0.000 description 2
- IRSCQMHQWWYFCW-UHFFFAOYSA-N ganciclovir Chemical compound O=C1NC(N)=NC2=C1N=CN2COC(CO)CO IRSCQMHQWWYFCW-UHFFFAOYSA-N 0.000 description 2
- 229960003923 gatifloxacin Drugs 0.000 description 2
- 229960002584 gefitinib Drugs 0.000 description 2
- XGALLCVXEZPNRQ-UHFFFAOYSA-N gefitinib Chemical compound C=12C=C(OCCCN3CCOCC3)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 XGALLCVXEZPNRQ-UHFFFAOYSA-N 0.000 description 2
- SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 description 2
- 229960005277 gemcitabine Drugs 0.000 description 2
- 229960003170 gemifloxacin Drugs 0.000 description 2
- ZRCVYEYHRGVLOC-HYARGMPZSA-N gemifloxacin Chemical compound C1C(CN)C(=N/OC)/CN1C(C(=C1)F)=NC2=C1C(=O)C(C(O)=O)=CN2C1CC1 ZRCVYEYHRGVLOC-HYARGMPZSA-N 0.000 description 2
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 2
- 229930182470 glycoside Natural products 0.000 description 2
- 239000002622 gonadotropin Substances 0.000 description 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 2
- 229960002885 histidine Drugs 0.000 description 2
- 229960002474 hydralazine Drugs 0.000 description 2
- 229960002003 hydrochlorothiazide Drugs 0.000 description 2
- 229960000908 idarubicin Drugs 0.000 description 2
- KTUFNOKKBVMGRW-UHFFFAOYSA-N imatinib Chemical compound C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)C=C1 KTUFNOKKBVMGRW-UHFFFAOYSA-N 0.000 description 2
- 229960002411 imatinib Drugs 0.000 description 2
- 125000002883 imidazolyl group Chemical group 0.000 description 2
- 229960002751 imiquimod Drugs 0.000 description 2
- DOUYETYNHWVLEO-UHFFFAOYSA-N imiquimod Chemical compound C1=CC=CC2=C3N(CC(C)C)C=NC3=C(N)N=C21 DOUYETYNHWVLEO-UHFFFAOYSA-N 0.000 description 2
- 230000001976 improved effect Effects 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 229960002979 iopanoic acid Drugs 0.000 description 2
- 229940055052 isocaine Drugs 0.000 description 2
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 2
- 229960000310 isoleucine Drugs 0.000 description 2
- XVQUOJBERHHONY-UHFFFAOYSA-N isometheptene Chemical compound CNC(C)CCC=C(C)C XVQUOJBERHHONY-UHFFFAOYSA-N 0.000 description 2
- 229960003046 isometheptene Drugs 0.000 description 2
- 229960004427 isradipine Drugs 0.000 description 2
- JTEGQNOMFQHVDC-NKWVEPMBSA-N lamivudine Chemical compound O=C1N=C(N)C=CN1[C@H]1O[C@@H](CO)SC1 JTEGQNOMFQHVDC-NKWVEPMBSA-N 0.000 description 2
- 229960001627 lamivudine Drugs 0.000 description 2
- 229960003136 leucine Drugs 0.000 description 2
- 229950008325 levothyroxine Drugs 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- RLAWWYSOJDYHDC-BZSNNMDCSA-N lisinopril Chemical compound C([C@H](N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(O)=O)C(O)=O)CC1=CC=CC=C1 RLAWWYSOJDYHDC-BZSNNMDCSA-N 0.000 description 2
- 229960002394 lisinopril Drugs 0.000 description 2
- KSMAGQUYOIHWFS-UHFFFAOYSA-N lofexidine Chemical compound N=1CCNC=1C(C)OC1=C(Cl)C=CC=C1Cl KSMAGQUYOIHWFS-UHFFFAOYSA-N 0.000 description 2
- 229960005209 lofexidine Drugs 0.000 description 2
- ZEKZLJVOYLTDKK-UHFFFAOYSA-N lomefloxacin Chemical compound FC1=C2N(CC)C=C(C(O)=O)C(=O)C2=CC(F)=C1N1CCNC(C)C1 ZEKZLJVOYLTDKK-UHFFFAOYSA-N 0.000 description 2
- 229960002422 lomefloxacin Drugs 0.000 description 2
- 229940060963 lotronex Drugs 0.000 description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- IMYZQPCYWPFTAG-IQJOONFLSA-N mecamylamine Chemical compound C1C[C@@H]2C(C)(C)[C@@](NC)(C)[C@H]1C2 IMYZQPCYWPFTAG-IQJOONFLSA-N 0.000 description 2
- 229960002525 mecamylamine Drugs 0.000 description 2
- HYYBABOKPJLUIN-UHFFFAOYSA-N mefenamic acid Chemical compound CC1=CC=CC(NC=2C(=CC=CC=2)C(O)=O)=C1C HYYBABOKPJLUIN-UHFFFAOYSA-N 0.000 description 2
- HVGQWHMSVYODLJ-GFCCVEGCSA-N melanochrome Natural products CC1(C)Oc2cc3OC(=CC(=O)c3c(O)c2C[C@H]1O)CO HVGQWHMSVYODLJ-GFCCVEGCSA-N 0.000 description 2
- SGDBTWWWUNNDEQ-LBPRGKRZSA-N melphalan Chemical compound OC(=O)[C@@H](N)CC1=CC=C(N(CCCl)CCCl)C=C1 SGDBTWWWUNNDEQ-LBPRGKRZSA-N 0.000 description 2
- 229960001924 melphalan Drugs 0.000 description 2
- RXQCGGRTAILOIN-UHFFFAOYSA-N mephentermine Chemical compound CNC(C)(C)CC1=CC=CC=C1 RXQCGGRTAILOIN-UHFFFAOYSA-N 0.000 description 2
- 229960002342 mephentermine Drugs 0.000 description 2
- 229960003151 mercaptamine Drugs 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- 229960003663 metaraminol Drugs 0.000 description 2
- XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 description 2
- 229960003105 metformin Drugs 0.000 description 2
- OEHAYUOVELTAPG-UHFFFAOYSA-N methoxyphenamine Chemical compound CNC(C)CC1=CC=CC=C1OC OEHAYUOVELTAPG-UHFFFAOYSA-N 0.000 description 2
- VKQFCGNPDRICFG-UHFFFAOYSA-N methyl 2-methylpropyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OCC(C)C)C1C1=CC=CC=C1[N+]([O-])=O VKQFCGNPDRICFG-UHFFFAOYSA-N 0.000 description 2
- 229960001980 metirosine Drugs 0.000 description 2
- TTWJBBZEZQICBI-UHFFFAOYSA-N metoclopramide Chemical compound CCN(CC)CCNC(=O)C1=CC(Cl)=C(N)C=C1OC TTWJBBZEZQICBI-UHFFFAOYSA-N 0.000 description 2
- 229960004503 metoclopramide Drugs 0.000 description 2
- 229960001094 midodrine Drugs 0.000 description 2
- MGCQZNBCJBRZDT-UHFFFAOYSA-N midodrine hydrochloride Chemical compound [H+].[Cl-].COC1=CC=C(OC)C(C(O)CNC(=O)CN)=C1 MGCQZNBCJBRZDT-UHFFFAOYSA-N 0.000 description 2
- 229960002728 midodrine hydrochloride Drugs 0.000 description 2
- KKZJGLLVHKMTCM-UHFFFAOYSA-N mitoxantrone Chemical compound O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO KKZJGLLVHKMTCM-UHFFFAOYSA-N 0.000 description 2
- 229960001156 mitoxantrone Drugs 0.000 description 2
- 229960005170 moexipril Drugs 0.000 description 2
- 229960003702 moxifloxacin Drugs 0.000 description 2
- FABPRXSRWADJSP-MEDUHNTESA-N moxifloxacin Chemical compound COC1=C(N2C[C@H]3NCCC[C@H]3C2)C(F)=CC(C(C(C(O)=O)=C2)=O)=C1N2C1CC1 FABPRXSRWADJSP-MEDUHNTESA-N 0.000 description 2
- DPBLXKKOBLCELK-UHFFFAOYSA-N n-pentylamine Natural products CCCCCN DPBLXKKOBLCELK-UHFFFAOYSA-N 0.000 description 2
- 229960005254 naratriptan Drugs 0.000 description 2
- UNHGSHHVDNGCFN-UHFFFAOYSA-N naratriptan Chemical compound C=12[CH]C(CCS(=O)(=O)NC)=CC=C2N=CC=1C1CCN(C)CC1 UNHGSHHVDNGCFN-UHFFFAOYSA-N 0.000 description 2
- 201000003631 narcolepsy Diseases 0.000 description 2
- IXOXBSCIXZEQEQ-UHTZMRCNSA-N nelarabine Chemical compound C1=NC=2C(OC)=NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@@H]1O IXOXBSCIXZEQEQ-UHTZMRCNSA-N 0.000 description 2
- 229960000801 nelarabine Drugs 0.000 description 2
- QEFAQIPZVLVERP-UHFFFAOYSA-N nepafenac Chemical compound NC(=O)CC1=CC=CC(C(=O)C=2C=CC=CC=2)=C1N QEFAQIPZVLVERP-UHFFFAOYSA-N 0.000 description 2
- 229960001002 nepafenac Drugs 0.000 description 2
- 230000002232 neuromuscular Effects 0.000 description 2
- 229960001783 nicardipine Drugs 0.000 description 2
- 239000000181 nicotinic agonist Substances 0.000 description 2
- 229960000227 nisoldipine Drugs 0.000 description 2
- 229950004211 nisoxetine Drugs 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- SGXXNSQHWDMGGP-IZZDOVSWSA-N nizatidine Chemical compound [O-][N+](=O)\C=C(/NC)NCCSCC1=CSC(CN(C)C)=N1 SGXXNSQHWDMGGP-IZZDOVSWSA-N 0.000 description 2
- 229960004872 nizatidine Drugs 0.000 description 2
- 239000012434 nucleophilic reagent Substances 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 235000019198 oils Nutrition 0.000 description 2
- KVWDHTXUZHCGIO-UHFFFAOYSA-N olanzapine Chemical compound C1CN(C)CCN1C1=NC2=CC=CC=C2NC2=C1C=C(C)S2 KVWDHTXUZHCGIO-UHFFFAOYSA-N 0.000 description 2
- 229960005017 olanzapine Drugs 0.000 description 2
- VTRAEEWXHOVJFV-UHFFFAOYSA-N olmesartan Chemical compound CCCC1=NC(C(C)(C)O)=C(C(O)=O)N1CC1=CC=C(C=2C(=CC=CC=2)C=2NN=NN=2)C=C1 VTRAEEWXHOVJFV-UHFFFAOYSA-N 0.000 description 2
- 229960005117 olmesartan Drugs 0.000 description 2
- 229960000381 omeprazole Drugs 0.000 description 2
- SBQLYHNEIUGQKH-UHFFFAOYSA-N omeprazole Chemical compound N1=C2[CH]C(OC)=CC=C2N=C1S(=O)CC1=NC=C(C)C(OC)=C1C SBQLYHNEIUGQKH-UHFFFAOYSA-N 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 229960003752 oseltamivir Drugs 0.000 description 2
- VSZGPKBBMSAYNT-RRFJBIMHSA-N oseltamivir Chemical compound CCOC(=O)C1=C[C@@H](OC(CC)CC)[C@H](NC(C)=O)[C@@H](N)C1 VSZGPKBBMSAYNT-RRFJBIMHSA-N 0.000 description 2
- DWAFYCQODLXJNR-BNTLRKBRSA-L oxaliplatin Chemical compound O1C(=O)C(=O)O[Pt]11N[C@@H]2CCCC[C@H]2N1 DWAFYCQODLXJNR-BNTLRKBRSA-L 0.000 description 2
- 229960001756 oxaliplatin Drugs 0.000 description 2
- XCGYUJZMCCFSRP-UHFFFAOYSA-N oxamniquine Chemical compound OCC1=C([N+]([O-])=O)C=C2NC(CNC(C)C)CCC2=C1 XCGYUJZMCCFSRP-UHFFFAOYSA-N 0.000 description 2
- 229960000462 oxamniquine Drugs 0.000 description 2
- 125000002971 oxazolyl group Chemical group 0.000 description 2
- GDYUVHBMFVMBAF-LIRRHRJNSA-N oxyfedrine Chemical compound COC1=CC=CC(C(=O)CCN[C@@H](C)[C@H](O)C=2C=CC=CC=2)=C1 GDYUVHBMFVMBAF-LIRRHRJNSA-N 0.000 description 2
- 229960001818 oxyfedrine Drugs 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- WYWIFABBXFUGLM-UHFFFAOYSA-N oxymetazoline Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C)=C1CC1=NCCN1 WYWIFABBXFUGLM-UHFFFAOYSA-N 0.000 description 2
- WRUUGTRCQOWXEG-UHFFFAOYSA-N pamidronate Chemical compound NCCC(O)(P(O)(O)=O)P(O)(O)=O WRUUGTRCQOWXEG-UHFFFAOYSA-N 0.000 description 2
- 229960003978 pamidronic acid Drugs 0.000 description 2
- 229960005019 pantoprazole Drugs 0.000 description 2
- 229960003349 pemetrexed disodium Drugs 0.000 description 2
- 229960001179 penciclovir Drugs 0.000 description 2
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 2
- CYXKNKQEMFBLER-UHFFFAOYSA-N perhexiline Chemical compound C1CCCNC1CC(C1CCCCC1)C1CCCCC1 CYXKNKQEMFBLER-UHFFFAOYSA-N 0.000 description 2
- 229960000989 perhexiline Drugs 0.000 description 2
- 229960004803 perhexiline maleate Drugs 0.000 description 2
- 229960002582 perindopril Drugs 0.000 description 2
- IPVQLZZIHOAWMC-QXKUPLGCSA-N perindopril Chemical compound C1CCC[C@H]2C[C@@H](C(O)=O)N(C(=O)[C@H](C)N[C@@H](CCC)C(=O)OCC)[C@H]21 IPVQLZZIHOAWMC-QXKUPLGCSA-N 0.000 description 2
- 238000001050 pharmacotherapy Methods 0.000 description 2
- 229960003209 phenmetrazine Drugs 0.000 description 2
- 229960001999 phentolamine Drugs 0.000 description 2
- MRBDMNSDAVCSSF-UHFFFAOYSA-N phentolamine Chemical compound C1=CC(C)=CC=C1N(C=1C=C(O)C=CC=1)CC1=NCCN1 MRBDMNSDAVCSSF-UHFFFAOYSA-N 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 2
- DLNKOYKMWOXYQA-APPZFPTMSA-N phenylpropanolamine Chemical compound C[C@@H](N)[C@H](O)C1=CC=CC=C1 DLNKOYKMWOXYQA-APPZFPTMSA-N 0.000 description 2
- 229960000395 phenylpropanolamine Drugs 0.000 description 2
- JOHZPMXAZQZXHR-UHFFFAOYSA-N pipemidic acid Chemical compound N1=C2N(CC)C=C(C(O)=O)C(=O)C2=CN=C1N1CCNCC1 JOHZPMXAZQZXHR-UHFFFAOYSA-N 0.000 description 2
- 229960001732 pipemidic acid Drugs 0.000 description 2
- XSWHNYGMWWVAIE-UHFFFAOYSA-N pipradrol Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(O)C1CCCCN1 XSWHNYGMWWVAIE-UHFFFAOYSA-N 0.000 description 2
- 229960000753 pipradrol Drugs 0.000 description 2
- 229920000768 polyamine Polymers 0.000 description 2
- 239000003450 potassium channel blocker Substances 0.000 description 2
- WSVOMANDJDYYEY-CWNVBEKCSA-N prednylidene Chemical group O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](C(=C)C4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 WSVOMANDJDYYEY-CWNVBEKCSA-N 0.000 description 2
- 229960001917 prednylidene Drugs 0.000 description 2
- INDBQLZJXZLFIT-UHFFFAOYSA-N primaquine Chemical compound N1=CC=CC2=CC(OC)=CC(NC(C)CCCN)=C21 INDBQLZJXZLFIT-UHFFFAOYSA-N 0.000 description 2
- 229960005179 primaquine Drugs 0.000 description 2
- REQCZEXYDRLIBE-UHFFFAOYSA-N procainamide Chemical compound CCN(CC)CCNC(=O)C1=CC=C(N)C=C1 REQCZEXYDRLIBE-UHFFFAOYSA-N 0.000 description 2
- 229960000244 procainamide Drugs 0.000 description 2
- CPTBDICYNRMXFX-UHFFFAOYSA-N procarbazine Chemical compound CNNCC1=CC=C(C(=O)NC(C)C)C=C1 CPTBDICYNRMXFX-UHFFFAOYSA-N 0.000 description 2
- 229960000624 procarbazine Drugs 0.000 description 2
- JWHAUXFOSRPERK-UHFFFAOYSA-N propafenone Chemical compound CCCNCC(O)COC1=CC=CC=C1C(=O)CCC1=CC=CC=C1 JWHAUXFOSRPERK-UHFFFAOYSA-N 0.000 description 2
- 229960000203 propafenone Drugs 0.000 description 2
- JCRIVQIOJSSCQD-UHFFFAOYSA-N propylhexedrine Chemical compound CNC(C)CC1CCCCC1 JCRIVQIOJSSCQD-UHFFFAOYSA-N 0.000 description 2
- 229960000786 propylhexedrine Drugs 0.000 description 2
- 229960003908 pseudoephedrine Drugs 0.000 description 2
- KWGRBVOPPLSCSI-WCBMZHEXSA-N pseudoephedrine Chemical compound CN[C@@H](C)[C@@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-WCBMZHEXSA-N 0.000 description 2
- 125000004076 pyridyl group Chemical group 0.000 description 2
- WKSAUQYGYAYLPV-UHFFFAOYSA-N pyrimethamine Chemical compound CCC1=NC(N)=NC(N)=C1C1=CC=C(Cl)C=C1 WKSAUQYGYAYLPV-UHFFFAOYSA-N 0.000 description 2
- 229960000611 pyrimethamine Drugs 0.000 description 2
- 229960001455 quinapril Drugs 0.000 description 2
- JSDRRTOADPPCHY-HSQYWUDLSA-N quinapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](CC2=CC=CC=C2C1)C(O)=O)CC1=CC=CC=C1 JSDRRTOADPPCHY-HSQYWUDLSA-N 0.000 description 2
- AGMMTXLNIQSRCG-UHFFFAOYSA-N quinethazone Chemical compound NS(=O)(=O)C1=C(Cl)C=C2NC(CC)NC(=O)C2=C1 AGMMTXLNIQSRCG-UHFFFAOYSA-N 0.000 description 2
- 229960000577 quinethazone Drugs 0.000 description 2
- 125000005493 quinolyl group Chemical group 0.000 description 2
- YREYEVIYCVEVJK-UHFFFAOYSA-N rabeprazole Chemical compound COCCCOC1=CC=NC(CS(=O)C=2NC3=CC=CC=C3N=2)=C1C YREYEVIYCVEVJK-UHFFFAOYSA-N 0.000 description 2
- 229960004157 rabeprazole Drugs 0.000 description 2
- 229950003070 racephedrine Drugs 0.000 description 2
- 229960003401 ramipril Drugs 0.000 description 2
- HDACQVRGBOVJII-JBDAPHQKSA-N ramipril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](C[C@@H]2CCC[C@@H]21)C(O)=O)CC1=CC=CC=C1 HDACQVRGBOVJII-JBDAPHQKSA-N 0.000 description 2
- GGWBHVILAJZWKJ-KJEVSKRMSA-N ranitidine hydrochloride Chemical compound [H+].[Cl-].[O-][N+](=O)\C=C(/NC)NCCSCC1=CC=C(CN(C)C)O1 GGWBHVILAJZWKJ-KJEVSKRMSA-N 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 210000000664 rectum Anatomy 0.000 description 2
- 238000012827 research and development Methods 0.000 description 2
- 239000003340 retarding agent Substances 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 238000012552 review Methods 0.000 description 2
- 229960000425 rizatriptan Drugs 0.000 description 2
- TXHZXHICDBAVJW-UHFFFAOYSA-N rizatriptan Chemical compound C=1[C]2C(CCN(C)C)=CN=C2C=CC=1CN1C=NC=N1 TXHZXHICDBAVJW-UHFFFAOYSA-N 0.000 description 2
- 235000012045 salad Nutrition 0.000 description 2
- 210000002955 secretory cell Anatomy 0.000 description 2
- 229960003693 sevelamer Drugs 0.000 description 2
- ZNSIZMQNQCNRBW-UHFFFAOYSA-N sevelamer Chemical compound NCC=C.ClCC1CO1 ZNSIZMQNQCNRBW-UHFFFAOYSA-N 0.000 description 2
- 229960005456 sisomicin Drugs 0.000 description 2
- URWAJWIAIPFPJE-YFMIWBNJSA-N sisomycin Chemical compound O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H](CC=C(CN)O2)N)[C@@H](N)C[C@H]1N URWAJWIAIPFPJE-YFMIWBNJSA-N 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000001488 sodium phosphate Substances 0.000 description 2
- 229910000162 sodium phosphate Inorganic materials 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 229960004954 sparfloxacin Drugs 0.000 description 2
- DZZWHBIBMUVIIW-DTORHVGOSA-N sparfloxacin Chemical compound C1[C@@H](C)N[C@@H](C)CN1C1=C(F)C(N)=C2C(=O)C(C(O)=O)=CN(C3CC3)C2=C1F DZZWHBIBMUVIIW-DTORHVGOSA-N 0.000 description 2
- UNFWWIHTNXNPBV-WXKVUWSESA-N spectinomycin Chemical compound O([C@@H]1[C@@H](NC)[C@@H](O)[C@H]([C@@H]([C@H]1O1)O)NC)[C@]2(O)[C@H]1O[C@H](C)CC2=O UNFWWIHTNXNPBV-WXKVUWSESA-N 0.000 description 2
- 229960000268 spectinomycin Drugs 0.000 description 2
- ATHGHQPFGPMSJY-UHFFFAOYSA-N spermidine Chemical compound NCCCCNCCCN ATHGHQPFGPMSJY-UHFFFAOYSA-N 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 229960002076 sulfacytine Drugs 0.000 description 2
- SIBQAECNSSQUOD-UHFFFAOYSA-N sulfacytine Chemical compound O=C1N(CC)C=CC(NS(=O)(=O)C=2C=CC(N)=CC=2)=N1 SIBQAECNSSQUOD-UHFFFAOYSA-N 0.000 description 2
- 229960002135 sulfadimidine Drugs 0.000 description 2
- BRBKOPJOKNSWSG-UHFFFAOYSA-N sulfaguanidine Chemical compound NC(=N)NS(=O)(=O)C1=CC=C(N)C=C1 BRBKOPJOKNSWSG-UHFFFAOYSA-N 0.000 description 2
- 229960004257 sulfaguanidine Drugs 0.000 description 2
- IJZUQDQOAFUFJY-UHFFFAOYSA-N sulfaguanole Chemical compound O1C(C)=C(C)N=C1N\C(N)=N\S(=O)(=O)C1=CC=C(N)C=C1 IJZUQDQOAFUFJY-UHFFFAOYSA-N 0.000 description 2
- 229950008582 sulfaguanole Drugs 0.000 description 2
- QPPBRPIAZZHUNT-UHFFFAOYSA-N sulfamerazine Chemical compound CC1=CC=NC(NS(=O)(=O)C=2C=CC(N)=CC=2)=N1 QPPBRPIAZZHUNT-UHFFFAOYSA-N 0.000 description 2
- 229960002597 sulfamerazine Drugs 0.000 description 2
- ASWVTGNCAZCNNR-UHFFFAOYSA-N sulfamethazine Chemical compound CC1=CC(C)=NC(NS(=O)(=O)C=2C=CC(N)=CC=2)=N1 ASWVTGNCAZCNNR-UHFFFAOYSA-N 0.000 description 2
- 229960005404 sulfamethoxazole Drugs 0.000 description 2
- GPTONYMQFTZPKC-UHFFFAOYSA-N sulfamethoxydiazine Chemical compound N1=CC(OC)=CN=C1NS(=O)(=O)C1=CC=C(N)C=C1 GPTONYMQFTZPKC-UHFFFAOYSA-N 0.000 description 2
- VLYWMPOKSSWJAL-UHFFFAOYSA-N sulfamethoxypyridazine Chemical compound N1=NC(OC)=CC=C1NS(=O)(=O)C1=CC=C(N)C=C1 VLYWMPOKSSWJAL-UHFFFAOYSA-N 0.000 description 2
- 229960004936 sulfamethoxypyridazine Drugs 0.000 description 2
- 229960001873 sulfametomidine Drugs 0.000 description 2
- 229960002229 sulfametoxydiazine Drugs 0.000 description 2
- JLKIGFTWXXRPMT-UHFFFAOYSA-N sulphamethoxazole Chemical compound O1C(C)=CC(NS(=O)(=O)C=2C=CC(N)=CC=2)=N1 JLKIGFTWXXRPMT-UHFFFAOYSA-N 0.000 description 2
- 229960003708 sumatriptan Drugs 0.000 description 2
- KQKPFRSPSRPDEB-UHFFFAOYSA-N sumatriptan Chemical compound CNS(=O)(=O)CC1=CC=C2NC=C(CCN(C)C)C2=C1 KQKPFRSPSRPDEB-UHFFFAOYSA-N 0.000 description 2
- 210000000225 synapse Anatomy 0.000 description 2
- 230000005062 synaptic transmission Effects 0.000 description 2
- YLJREFDVOIBQDA-UHFFFAOYSA-N tacrine Chemical compound C1=CC=C2C(N)=C(CCCC3)C3=NC2=C1 YLJREFDVOIBQDA-UHFFFAOYSA-N 0.000 description 2
- 229960001685 tacrine Drugs 0.000 description 2
- WOXKDUGGOYFFRN-IIBYNOLFSA-N tadalafil Chemical compound C1=C2OCOC2=CC([C@@H]2C3=C(C4=CC=CC=C4N3)C[C@H]3N2C(=O)CN(C3=O)C)=C1 WOXKDUGGOYFFRN-IIBYNOLFSA-N 0.000 description 2
- 229960002613 tamsulosin Drugs 0.000 description 2
- IKBKZGMPCYNSLU-RGVLZGJSSA-N tegaserod Chemical compound C1=C(OC)C=C2C(/C=N/NC(=N)NCCCCC)=CNC2=C1 IKBKZGMPCYNSLU-RGVLZGJSSA-N 0.000 description 2
- 229960002876 tegaserod Drugs 0.000 description 2
- 229960004556 tenofovir Drugs 0.000 description 2
- VCMJCVGFSROFHV-WZGZYPNHSA-N tenofovir disoproxil fumarate Chemical compound OC(=O)\C=C\C(O)=O.N1=CN=C2N(C[C@@H](C)OCP(=O)(OCOC(=O)OC(C)C)OCOC(=O)OC(C)C)C=NC2=C1N VCMJCVGFSROFHV-WZGZYPNHSA-N 0.000 description 2
- VCKUSRYTPJJLNI-UHFFFAOYSA-N terazosin Chemical compound N=1C(N)=C2C=C(OC)C(OC)=CC2=NC=1N(CC1)CCN1C(=O)C1CCCO1 VCKUSRYTPJJLNI-UHFFFAOYSA-N 0.000 description 2
- 229960001693 terazosin Drugs 0.000 description 2
- 125000005306 thianaphthenyl group Chemical group 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- DZLNHFMRPBPULJ-UHFFFAOYSA-N thioproline Chemical compound OC(=O)C1CSCN1 DZLNHFMRPBPULJ-UHFFFAOYSA-N 0.000 description 2
- XUIIKFGFIJCVMT-UHFFFAOYSA-N thyroxine-binding globulin Natural products IC1=CC(CC([NH3+])C([O-])=O)=CC(I)=C1OC1=CC(I)=C(O)C(I)=C1 XUIIKFGFIJCVMT-UHFFFAOYSA-N 0.000 description 2
- FPZLLRFZJZRHSY-HJYUBDRYSA-N tigecycline Chemical compound C([C@H]1C2)C3=C(N(C)C)C=C(NC(=O)CNC(C)(C)C)C(O)=C3C(=O)C1=C(O)[C@@]1(O)[C@@H]2[C@H](N(C)C)C(O)=C(C(N)=O)C1=O FPZLLRFZJZRHSY-HJYUBDRYSA-N 0.000 description 2
- 229960004089 tigecycline Drugs 0.000 description 2
- 229950001139 timonacic Drugs 0.000 description 2
- 229950010298 tinoridine Drugs 0.000 description 2
- PFENFDGYVLAFBR-UHFFFAOYSA-N tinoridine Chemical compound C1CC=2C(C(=O)OCC)=C(N)SC=2CN1CC1=CC=CC=C1 PFENFDGYVLAFBR-UHFFFAOYSA-N 0.000 description 2
- COKMIXFXJJXBQG-NRFANRHFSA-N tirofiban Chemical compound C1=CC(C[C@H](NS(=O)(=O)CCCC)C(O)=O)=CC=C1OCCCCC1CCNCC1 COKMIXFXJJXBQG-NRFANRHFSA-N 0.000 description 2
- 229960003425 tirofiban Drugs 0.000 description 2
- XFYDIVBRZNQMJC-UHFFFAOYSA-N tizanidine Chemical compound ClC=1C=CC2=NSN=C2C=1NC1=NCCN1 XFYDIVBRZNQMJC-UHFFFAOYSA-N 0.000 description 2
- 229960000488 tizanidine Drugs 0.000 description 2
- JIVZKJJQOZQXQB-UHFFFAOYSA-N tolazoline Chemical compound C=1C=CC=CC=1CC1=NCCN1 JIVZKJJQOZQXQB-UHFFFAOYSA-N 0.000 description 2
- 229960002312 tolazoline Drugs 0.000 description 2
- 229960005461 torasemide Drugs 0.000 description 2
- 231100000027 toxicology Toxicity 0.000 description 2
- RGVPOXRFEPSFGH-AWEZNQCLSA-N tretoquinol Chemical compound COC1=C(OC)C(OC)=CC(C[C@H]2C3=CC(O)=C(O)C=C3CCN2)=C1 RGVPOXRFEPSFGH-AWEZNQCLSA-N 0.000 description 2
- 229960005204 tretoquinol Drugs 0.000 description 2
- LMJSLTNSBFUCMU-UHFFFAOYSA-N trichlormethiazide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NC(C(Cl)Cl)NS2(=O)=O LMJSLTNSBFUCMU-UHFFFAOYSA-N 0.000 description 2
- 229960004813 trichlormethiazide Drugs 0.000 description 2
- 229960001124 trientine Drugs 0.000 description 2
- 150000004684 trihydrates Chemical class 0.000 description 2
- IEDVJHCEMCRBQM-UHFFFAOYSA-N trimethoprim Chemical compound COC1=C(OC)C(OC)=CC(CC=2C(=NC(N)=NC=2)N)=C1 IEDVJHCEMCRBQM-UHFFFAOYSA-N 0.000 description 2
- 229960001082 trimethoprim Drugs 0.000 description 2
- NOYPYLRCIDNJJB-UHFFFAOYSA-N trimetrexate Chemical compound COC1=C(OC)C(OC)=CC(NCC=2C(=C3C(N)=NC(N)=NC3=CC=2)C)=C1 NOYPYLRCIDNJJB-UHFFFAOYSA-N 0.000 description 2
- 229960001099 trimetrexate Drugs 0.000 description 2
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 2
- 229960000497 trovafloxacin Drugs 0.000 description 2
- 229960001341 troxipide Drugs 0.000 description 2
- 229960004799 tryptophan Drugs 0.000 description 2
- 238000007039 two-step reaction Methods 0.000 description 2
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 2
- 229960002149 valganciclovir Drugs 0.000 description 2
- 229960004699 valsartan Drugs 0.000 description 2
- SJSNUMAYCRRIOM-QFIPXVFZSA-N valsartan Chemical compound C1=CC(CN(C(=O)CCCC)[C@@H](C(C)C)C(O)=O)=CC=C1C1=CC=CC=C1C1=NN=N[N]1 SJSNUMAYCRRIOM-QFIPXVFZSA-N 0.000 description 2
- 229960002381 vardenafil Drugs 0.000 description 2
- 229960001360 zolmitriptan Drugs 0.000 description 2
- UTAZCRNOSWWEFR-ZDUSSCGKSA-N zolmitriptan Chemical compound C=1[C]2C(CCN(C)C)=CN=C2C=CC=1C[C@H]1COC(=O)N1 UTAZCRNOSWWEFR-ZDUSSCGKSA-N 0.000 description 2
- XWTYSIMOBUGWOL-UHFFFAOYSA-N (+-)-Terbutaline Chemical compound CC(C)(C)NCC(O)C1=CC(O)=CC(O)=C1 XWTYSIMOBUGWOL-UHFFFAOYSA-N 0.000 description 1
- SUHGRZPINGKYNV-GJZGRUSLSA-N (1R,3S)-1-(aminomethyl)-3-phenyl-3,4-dihydro-1H-2-benzopyran-5,6-diol Chemical compound C1([C@H]2O[C@H](C3=CC=C(O)C(O)=C3C2)CN)=CC=CC=C1 SUHGRZPINGKYNV-GJZGRUSLSA-N 0.000 description 1
- BWHPNJVKFAPVOG-QYFJGNGUSA-N (1R,3S)-3-(adamantan-1-yl)-1-(aminomethyl)-3,4-dihydroisochromene-5,6-diol hydrochloride Chemical compound Cl.C1C(C2)CC(C3)CC2CC13[C@H]1O[C@@H](CN)C2=CC=C(O)C(O)=C2C1 BWHPNJVKFAPVOG-QYFJGNGUSA-N 0.000 description 1
- GGMYWPBNZXRMME-UHFFFAOYSA-N (1RS,2SR)-1-Amino-1,3-cyclobutanedicarboxylic acid Natural products OC(=O)C1(N)CC(C(O)=O)C1 GGMYWPBNZXRMME-UHFFFAOYSA-N 0.000 description 1
- VLZBRVJVCCNPRJ-KPHUOKFYSA-N (1S,2S)-2-[(1S)-1-amino-1-carboxy-2-(9H-xanthen-9-yl)ethyl]-1-cyclopropanecarboxylic acid Chemical compound C([C@@H]1[C@](CC2C3=CC=CC=C3OC3=CC=CC=C32)(N)C(O)=O)[C@@H]1C(O)=O VLZBRVJVCCNPRJ-KPHUOKFYSA-N 0.000 description 1
- KFACHLANPCGTFI-FVSJBQLASA-N (1S,2S)-2-[(1S)-1-amino-1-carboxyethyl]-1-cyclopropanecarboxylic acid Chemical compound OC(=O)[C@](N)(C)[C@H]1C[C@@H]1C(O)=O KFACHLANPCGTFI-FVSJBQLASA-N 0.000 description 1
- YFYNOWXBIBKGHB-FBCQKBJTSA-N (1s,3r)-1-aminocyclopentane-1,3-dicarboxylic acid Chemical compound OC(=O)[C@]1(N)CC[C@@H](C(O)=O)C1 YFYNOWXBIBKGHB-FBCQKBJTSA-N 0.000 description 1
- VXLBSYHAEKDUSU-JXMROGBWSA-N (2e)-2-(fluoromethylidene)-4-(4-fluorophenyl)butan-1-amine Chemical compound NC\C(=C\F)CCC1=CC=C(F)C=C1 VXLBSYHAEKDUSU-JXMROGBWSA-N 0.000 description 1
- YWPHCCPCQOJSGZ-LLVKDONJSA-N (2r)-2-[(2-ethoxyphenoxy)methyl]morpholine Chemical compound CCOC1=CC=CC=C1OC[C@@H]1OCCNC1 YWPHCCPCQOJSGZ-LLVKDONJSA-N 0.000 description 1
- JMVIGOFRIJJUAW-PWNYCUMCSA-N (2r,4r)-azetidine-2,4-dicarboxylic acid Chemical compound OC(=O)[C@H]1C[C@H](C(O)=O)N1 JMVIGOFRIJJUAW-PWNYCUMCSA-N 0.000 description 1
- XTBQNQMNFXNGLR-MKSBGGEFSA-N (2s)-1-(2-ethylphenoxy)-3-[[(1s)-1,2,3,4-tetrahydronaphthalen-1-yl]amino]propan-2-ol;oxalic acid Chemical compound OC(=O)C(O)=O.CCC1=CC=CC=C1OC[C@@H](O)CN[C@@H]1C2=CC=CC=C2CCC1 XTBQNQMNFXNGLR-MKSBGGEFSA-N 0.000 description 1
- HONKEGXLWUDTCF-YFKPBYRVSA-N (2s)-2-amino-2-methyl-4-phosphonobutanoic acid Chemical compound OC(=O)[C@](N)(C)CCP(O)(O)=O HONKEGXLWUDTCF-YFKPBYRVSA-N 0.000 description 1
- VBRJFXSFCYEZMQ-HNNXBMFYSA-N (2s)-2-amino-3-[3-(2-chlorophenyl)-5-(phosphonomethyl)phenyl]propanoic acid Chemical compound OC(=O)[C@@H](N)CC1=CC(CP(O)(O)=O)=CC(C=2C(=CC=CC=2)Cl)=C1 VBRJFXSFCYEZMQ-HNNXBMFYSA-N 0.000 description 1
- NYZFUZCCDOSQBG-AWEZNQCLSA-N (2s)-2-amino-3-[5-(2,4-dichlorophenyl)-2-hydroxy-3-(phosphonomethyl)phenyl]propanoic acid Chemical compound OP(=O)(O)CC1=C(O)C(C[C@H](N)C(O)=O)=CC(C=2C(=CC(Cl)=CC=2)Cl)=C1 NYZFUZCCDOSQBG-AWEZNQCLSA-N 0.000 description 1
- JXJHGTYDEKHEIX-WNQIDUERSA-N (2s)-2-amino-3-hydroxypropanoic acid;benzene Chemical compound C1=CC=CC=C1.OC[C@H](N)C(O)=O JXJHGTYDEKHEIX-WNQIDUERSA-N 0.000 description 1
- BYOBCYXURWDEDS-IUCAKERBSA-N (2s,3s)-2-amino-3-phenylmethoxybutanedioic acid Chemical compound OC(=O)[C@@H](N)[C@@H](C(O)=O)OCC1=CC=CC=C1 BYOBCYXURWDEDS-IUCAKERBSA-N 0.000 description 1
- UCKHICKHGAOGAP-KGLIPLIRSA-N (2s,4r)-5,7-dichloro-4-(phenylcarbamoylamino)-1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound N([C@@H]1C[C@H](NC2=CC(Cl)=CC(Cl)=C21)C(=O)O)C(=O)NC1=CC=CC=C1 UCKHICKHGAOGAP-KGLIPLIRSA-N 0.000 description 1
- XNQIOISZPFVUFG-RXMQYKEDSA-N (R)-alpha-methylhistamine Chemical compound C[C@@H](N)CC1=CN=CN1 XNQIOISZPFVUFG-RXMQYKEDSA-N 0.000 description 1
- QHGUCRYDKWKLMG-QMMMGPOBSA-N (R)-octopamine Chemical compound NC[C@H](O)C1=CC=C(O)C=C1 QHGUCRYDKWKLMG-QMMMGPOBSA-N 0.000 description 1
- XHGLVMDBZZZXDP-LLVKDONJSA-N (R)-salsolinol-1-carboxylate zwitterion Chemical compound OC1=C(O)C=C2[C@](C)(C(O)=O)NCCC2=C1 XHGLVMDBZZZXDP-LLVKDONJSA-N 0.000 description 1
- FMKJUUQOYOHLTF-OWOJBTEDSA-N (e)-4-azaniumylbut-2-enoate Chemical compound NC\C=C\C(O)=O FMKJUUQOYOHLTF-OWOJBTEDSA-N 0.000 description 1
- ODAOZWTYNWZSBY-SPIKMXEPSA-N (z)-but-2-enedioic acid;6-[2-(1h-imidazol-5-yl)ethylamino]-n-[4-(trifluoromethyl)phenyl]heptanamide Chemical compound OC(=O)\C=C/C(O)=O.OC(=O)\C=C/C(O)=O.C=1N=CNC=1CCNC(C)CCCCC(=O)NC1=CC=C(C(F)(F)F)C=C1 ODAOZWTYNWZSBY-SPIKMXEPSA-N 0.000 description 1
- KKIMDKMETPPURN-UHFFFAOYSA-N 1-(3-(trifluoromethyl)phenyl)piperazine Chemical compound FC(F)(F)C1=CC=CC(N2CCNCC2)=C1 KKIMDKMETPPURN-UHFFFAOYSA-N 0.000 description 1
- VHFVKMTVMIZMIK-UHFFFAOYSA-N 1-(3-chlorophenyl)piperazine Chemical compound ClC1=CC=CC(N2CCNCC2)=C1 VHFVKMTVMIZMIK-UHFFFAOYSA-N 0.000 description 1
- JBHLYIVFFLNISJ-UHFFFAOYSA-N 1-(4-amino-5-chloro-2-methoxyphenyl)-3-(1-butyl-4-piperidinyl)-1-propanone Chemical compound C1CN(CCCC)CCC1CCC(=O)C1=CC(Cl)=C(N)C=C1OC JBHLYIVFFLNISJ-UHFFFAOYSA-N 0.000 description 1
- MJKADKZSYQWGLL-UHFFFAOYSA-N 1-(4-aminophenyl)-7,8-dimethoxy-3,5-dihydro-2,3-benzodiazepin-4-one Chemical compound C1=2C=C(OC)C(OC)=CC=2CC(=O)NN=C1C1=CC=C(N)C=C1 MJKADKZSYQWGLL-UHFFFAOYSA-N 0.000 description 1
- XVTVPGKWYHWYAD-UHFFFAOYSA-N 1-(propan-2-ylamino)-3-[2-(1-pyrrolyl)phenoxy]-2-propanol Chemical compound CC(C)NCC(O)COC1=CC=CC=C1N1C=CC=C1 XVTVPGKWYHWYAD-UHFFFAOYSA-N 0.000 description 1
- FVTVMQPGKVHSEY-UHFFFAOYSA-N 1-AMINOCYCLOBUTANE CARBOXYLIC ACID Chemical compound OC(=O)C1(N)CCC1 FVTVMQPGKVHSEY-UHFFFAOYSA-N 0.000 description 1
- HTLWRKRZKFAAAH-UHFFFAOYSA-N 1-[2-[[3-(2-cyanophenoxy)-2-hydroxypropyl]amino]ethyl]-3-phenylurea Chemical compound C=1C=CC=C(C#N)C=1OCC(O)CNCCNC(=O)NC1=CC=CC=C1 HTLWRKRZKFAAAH-UHFFFAOYSA-N 0.000 description 1
- IUPKMXPUMPJRDV-UHFFFAOYSA-N 1-amino-5-bromopyrimidine-2,4-dione Chemical compound NN1C=C(Br)C(=O)NC1=O IUPKMXPUMPJRDV-UHFFFAOYSA-N 0.000 description 1
- JUDKOGFHZYMDMF-UHFFFAOYSA-N 1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine-7,8-diol Chemical compound C1=2C=C(O)C(O)=CC=2CCNCC1C1=CC=CC=C1 JUDKOGFHZYMDMF-UHFFFAOYSA-N 0.000 description 1
- SDQUDWYMWXUWPV-UHFFFAOYSA-N 2-(3-hydroxyanilino)acetic acid Chemical compound OC(=O)CNC1=CC=CC(O)=C1 SDQUDWYMWXUWPV-UHFFFAOYSA-N 0.000 description 1
- GJNNXIYZWIZFRH-UHFFFAOYSA-N 2-(pentylamino)acetamide Chemical compound CCCCCNCC(N)=O GJNNXIYZWIZFRH-UHFFFAOYSA-N 0.000 description 1
- ZTMODTQBGMQMDL-UHFFFAOYSA-N 2-[(4,7-dimethyl-1,2-benzoxazol-3-yl)oxy]ethanamine Chemical compound CC1=CC=C(C)C2=C1ON=C2OCCN ZTMODTQBGMQMDL-UHFFFAOYSA-N 0.000 description 1
- ZGGNJJJYUVRADP-ACJLOTCBSA-N 2-[4-[(2R)-2-[[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]propyl]phenoxy]acetic acid Chemical compound C([C@@H](C)NC[C@H](O)C=1C=C(Cl)C=CC=1)C1=CC=C(OCC(O)=O)C=C1 ZGGNJJJYUVRADP-ACJLOTCBSA-N 0.000 description 1
- RVMBDLSFFNKKLG-SFHVURJKSA-N 2-[4-[2-[[(2s)-2-hydroxy-3-phenoxypropyl]amino]ethoxy]phenoxy]-n-(2-methoxyethyl)acetamide Chemical compound C1=CC(OCC(=O)NCCOC)=CC=C1OCCNC[C@H](O)COC1=CC=CC=C1 RVMBDLSFFNKKLG-SFHVURJKSA-N 0.000 description 1
- UNIDAFCQFPGYJJ-UHFFFAOYSA-N 2-amino-2-(2-chloro-5-hydroxyphenyl)acetic acid Chemical compound OC(=O)C(N)C1=CC(O)=CC=C1Cl UNIDAFCQFPGYJJ-UHFFFAOYSA-N 0.000 description 1
- HOOWCUZPEFNHDT-UHFFFAOYSA-N 2-amino-2-(3,5-dihydroxyphenyl)acetic acid Chemical compound OC(=O)C(N)C1=CC(O)=CC(O)=C1 HOOWCUZPEFNHDT-UHFFFAOYSA-N 0.000 description 1
- LLEOLNUKLKCAFG-UHFFFAOYSA-N 2-amino-2-(3-methyl-4-phosphonophenyl)propanoic acid Chemical compound CC1=CC(C(C)(N)C(O)=O)=CC=C1P(O)(O)=O LLEOLNUKLKCAFG-UHFFFAOYSA-N 0.000 description 1
- PAONCRJPUQXPRW-UHFFFAOYSA-N 2-amino-2-(4-phosphonophenyl)propanoic acid Chemical compound OC(=O)C(N)(C)C1=CC=C(P(O)(O)=O)C=C1 PAONCRJPUQXPRW-UHFFFAOYSA-N 0.000 description 1
- MVDSFPIEJILRME-UHFFFAOYSA-N 2-amino-2-(4-sulfophenyl)propanoic acid Chemical compound OC(=O)C(N)(C)C1=CC=C(S(O)(=O)=O)C=C1 MVDSFPIEJILRME-UHFFFAOYSA-N 0.000 description 1
- IGODGTDUQSMDQU-UHFFFAOYSA-N 2-amino-2-cyclopropyl-2-(4-phosphonophenyl)acetic acid Chemical compound C=1C=C(P(O)(O)=O)C=CC=1C(N)(C(O)=O)C1CC1 IGODGTDUQSMDQU-UHFFFAOYSA-N 0.000 description 1
- GSFCOAGADOGIGE-UHFFFAOYSA-N 2-amino-2-methyl-3-phosphonooxypropanoic acid Chemical compound OC(=O)C(N)(C)COP(O)(O)=O GSFCOAGADOGIGE-UHFFFAOYSA-N 0.000 description 1
- PIXJURSCCVBKRF-UHFFFAOYSA-N 2-amino-3-(5-tert-butyl-3-oxo-4-isoxazolyl)propanoic acid Chemical compound CC(C)(C)C=1ONC(=O)C=1CC([NH3+])C([O-])=O PIXJURSCCVBKRF-UHFFFAOYSA-N 0.000 description 1
- ADVPTQAUNPRNPO-UHFFFAOYSA-N 2-azaniumyl-3-sulfinopropanoate Chemical compound OC(=O)C(N)CS(O)=O ADVPTQAUNPRNPO-UHFFFAOYSA-N 0.000 description 1
- GGALEXMXDMUMDM-UHFFFAOYSA-N 2-chloro-6-(4-piperidinylthio)pyridine Chemical compound ClC1=CC=CC(SC2CCNCC2)=N1 GGALEXMXDMUMDM-UHFFFAOYSA-N 0.000 description 1
- WYWNEDARFVJQSG-UHFFFAOYSA-N 2-methylserotonin Chemical compound C1=C(O)C=C2C(CCN)=C(C)NC2=C1 WYWNEDARFVJQSG-UHFFFAOYSA-N 0.000 description 1
- 150000005341 2-nitrobenzoic acids Chemical class 0.000 description 1
- FKHYYOUFMJBLAF-UHFFFAOYSA-N 3-(3,3-dimethyl-1-phenyl-2-benzothiophen-1-yl)-n-methylpropan-1-amine Chemical compound S1C(C)(C)C2=CC=CC=C2C1(CCCNC)C1=CC=CC=C1 FKHYYOUFMJBLAF-UHFFFAOYSA-N 0.000 description 1
- DBWPFHJYSTVBCZ-BYPYZUCNSA-N 3-(5-fluorouracil-1-yl)-L-alanine Chemical compound OC(=O)[C@@H](N)CN1C=C(F)C(=O)NC1=O DBWPFHJYSTVBCZ-BYPYZUCNSA-N 0.000 description 1
- XKFMBGWHHBCWCD-UHFFFAOYSA-N 3-(azetidin-2-ylmethoxy)pyridine Chemical compound C1CNC1COC1=CC=CN=C1 XKFMBGWHHBCWCD-UHFFFAOYSA-N 0.000 description 1
- FACUYWPMDKTVFU-BYPYZUCNSA-N 3-(uracil-1-yl)-L-alanine Chemical compound OC(=O)[C@@H](N)CN1C=CC(=O)NC1=O FACUYWPMDKTVFU-BYPYZUCNSA-N 0.000 description 1
- GJZVQXWEIYRHBE-UHFFFAOYSA-N 3-[(3,4-dichlorophenyl)methylamino]propyl-(diethoxymethyl)phosphinic acid Chemical compound CCOC(OCC)P(O)(=O)CCCNCC1=CC=C(Cl)C(Cl)=C1 GJZVQXWEIYRHBE-UHFFFAOYSA-N 0.000 description 1
- XKFMBGWHHBCWCD-QMMMGPOBSA-N 3-[[(2s)-azetidin-2-yl]methoxy]pyridine Chemical compound C([C@H]1NCC1)OC1=CC=CN=C1 XKFMBGWHHBCWCD-QMMMGPOBSA-N 0.000 description 1
- ONNMDRQRSGKZCN-UHFFFAOYSA-N 3-aminopropyl(butyl)phosphinic acid Chemical compound CCCCP(O)(=O)CCCN ONNMDRQRSGKZCN-UHFFFAOYSA-N 0.000 description 1
- XOESDNIUAWGCLU-UHFFFAOYSA-N 3-aminopropyl(cyclohexylmethyl)phosphinic acid Chemical compound NCCCP(O)(=O)CC1CCCCC1 XOESDNIUAWGCLU-UHFFFAOYSA-N 0.000 description 1
- XQJMXPAEFMWDOZ-UHFFFAOYSA-N 3exo-benzoyloxy-tropane Natural products CN1C(C2)CCC1CC2OC(=O)C1=CC=CC=C1 XQJMXPAEFMWDOZ-UHFFFAOYSA-N 0.000 description 1
- 239000003148 4 aminobutyric acid receptor blocking agent Substances 0.000 description 1
- AIEFWRHRHFRLFT-UHFFFAOYSA-N 4-(1-amino-1-carboxypropyl)benzoic acid Chemical compound CCC(N)(C(O)=O)C1=CC=C(C(O)=O)C=C1 AIEFWRHRHFRLFT-UHFFFAOYSA-N 0.000 description 1
- FVIVKIGLBDRWNR-UHFFFAOYSA-N 4-(2-fluorophenyl)-6-methyl-2-piperazin-1-ylthieno[2,3-d]pyrimidine Chemical compound N1=C2SC(C)=CC2=C(C=2C(=CC=CC=2)F)N=C1N1CCNCC1 FVIVKIGLBDRWNR-UHFFFAOYSA-N 0.000 description 1
- PCTRYMLLRKWXGF-UHFFFAOYSA-N 4-(butylamino)-1-ethyl-6-methyl-5-pyrazolo[3,4-b]pyridinecarboxylic acid ethyl ester Chemical compound CCCCNC1=C(C(=O)OCC)C(C)=NC2=C1C=NN2CC PCTRYMLLRKWXGF-UHFFFAOYSA-N 0.000 description 1
- SGIKDIUCJAUSRD-QMMMGPOBSA-N 4-[(s)-amino(carboxy)methyl]-3-methylbenzoic acid Chemical compound CC1=CC(C(O)=O)=CC=C1[C@H](N)C(O)=O SGIKDIUCJAUSRD-QMMMGPOBSA-N 0.000 description 1
- IJVMOGKBEVRBPP-UHFFFAOYSA-N 4-[amino(carboxy)methyl]phthalic acid Chemical compound OC(=O)C(N)C1=CC=C(C(O)=O)C(C(O)=O)=C1 IJVMOGKBEVRBPP-UHFFFAOYSA-N 0.000 description 1
- JDTZAGLGBRRCJT-UHFFFAOYSA-N 4-amino-7-hydroxy-2-methyl-5,6,7,8-tetrahydro-[1]benzothiolo[2,3-b]pyridine-3-carboxylic acid but-2-ynyl ester Chemical compound C1C(O)CCC2=C1SC1=NC(C)=C(C(=O)OCC#CC)C(N)=C12 JDTZAGLGBRRCJT-UHFFFAOYSA-N 0.000 description 1
- NUKYPUAOHBNCPY-UHFFFAOYSA-N 4-aminopyridine Chemical group NC1=CC=NC=C1 NUKYPUAOHBNCPY-UHFFFAOYSA-N 0.000 description 1
- LHVRFUVVRXGZPV-UHFFFAOYSA-N 5-(2-aminoethyl)-4-methyl-2-thiazolamine Chemical compound CC=1N=C(N)SC=1CCN LHVRFUVVRXGZPV-UHFFFAOYSA-N 0.000 description 1
- KSNXJLQDQOIRIP-UHFFFAOYSA-N 5-iodouracil Chemical compound IC1=CNC(=O)NC1=O KSNXJLQDQOIRIP-UHFFFAOYSA-N 0.000 description 1
- AXXYLTBQIQBTES-BYPYZUCNSA-N 5-iodowillardiine Chemical compound OC(=O)[C@@H](N)CN1C=C(I)C(=O)NC1=O AXXYLTBQIQBTES-BYPYZUCNSA-N 0.000 description 1
- KRVMLPUDAOWOGN-UHFFFAOYSA-N 5-methoxy-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole Chemical compound C12=CC(OC)=CC=C2NC=C1C1=CCNCC1 KRVMLPUDAOWOGN-UHFFFAOYSA-N 0.000 description 1
- GGDBEAVVGFNWIA-UHFFFAOYSA-N 6-nitro-2-(1-piperazinyl)quinoline Chemical compound C1=CC2=CC([N+](=O)[O-])=CC=C2N=C1N1CCNCC1 GGDBEAVVGFNWIA-UHFFFAOYSA-N 0.000 description 1
- VZRNTCHTJRLTMU-UHFFFAOYSA-N 7-chloro-3-methyl-3,4-dihydro-2H-1$l^{6},2,4-benzothiadiazine 1,1-dioxide Chemical compound C1=C(Cl)C=C2S(=O)(=O)NC(C)NC2=C1 VZRNTCHTJRLTMU-UHFFFAOYSA-N 0.000 description 1
- OFUDZKKOKPGXOH-UHFFFAOYSA-N 8-(4-aminophenyl)-5-methyl-N-propyl-5H-[1,3]dioxolo[4,5-g]phthalazine-6-carboxamide Chemical compound C12=CC=3OCOC=3C=C2C(C)N(C(=O)NCCC)N=C1C1=CC=C(N)C=C1 OFUDZKKOKPGXOH-UHFFFAOYSA-N 0.000 description 1
- JXBLEDCYKVWLJI-UHFFFAOYSA-N 8-[2-(2,3-dihydro-1,4-benzodioxin-3-ylmethylamino)ethyl]-8-azaspiro[4.5]decane-7,9-dione;methanesulfonic acid Chemical compound CS(O)(=O)=O.C1C(=O)N(CCNCC2OC3=CC=CC=C3OC2)C(=O)CC21CCCC2 JXBLEDCYKVWLJI-UHFFFAOYSA-N 0.000 description 1
- HCVRCHQFYYZPHT-UHFFFAOYSA-N 8-[4-(2,3-dihydro-1,4-benzodioxin-3-ylmethylamino)butyl]-8-azaspiro[4.5]decane-7,9-dione Chemical compound C1C(=O)N(CCCCNCC2OC3=CC=CC=C3OC2)C(=O)CC21CCCC2 HCVRCHQFYYZPHT-UHFFFAOYSA-N 0.000 description 1
- ZGXJTSGNIOSYLO-UHFFFAOYSA-N 88755TAZ87 Chemical compound NCC(=O)CCC(O)=O ZGXJTSGNIOSYLO-UHFFFAOYSA-N 0.000 description 1
- GUDVQJXODNJRIJ-CALCHBBNSA-N 9-[3-[(3S,5R)-3,5-dimethyl-1-piperazinyl]propyl]carbazole Chemical compound C1[C@@H](C)N[C@@H](C)CN1CCCN1C2=CC=CC=C2C2=CC=CC=C21 GUDVQJXODNJRIJ-CALCHBBNSA-N 0.000 description 1
- GHWJEDJMOVUXEC-UHFFFAOYSA-N 9-chloro-5-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine-7,8-diol Chemical compound C1NCCC=2C(Cl)=C(O)C(O)=CC=2C1C1=CC=CC=C1 GHWJEDJMOVUXEC-UHFFFAOYSA-N 0.000 description 1
- 229920000856 Amylose Polymers 0.000 description 1
- 108010087765 Antipain Proteins 0.000 description 1
- 108010039627 Aprotinin Proteins 0.000 description 1
- 102000003916 Arrestin Human genes 0.000 description 1
- 108090000328 Arrestin Proteins 0.000 description 1
- 206010003591 Ataxia Diseases 0.000 description 1
- VGGGPCQERPFHOB-MCIONIFRSA-N Bestatin Chemical compound CC(C)C[C@H](C(O)=O)NC(=O)[C@@H](O)[C@H](N)CC1=CC=CC=C1 VGGGPCQERPFHOB-MCIONIFRSA-N 0.000 description 1
- VGGGPCQERPFHOB-UHFFFAOYSA-N Bestatin Natural products CC(C)CC(C(O)=O)NC(=O)C(O)C(N)CC1=CC=CC=C1 VGGGPCQERPFHOB-UHFFFAOYSA-N 0.000 description 1
- DKHJWWRYTONYHB-UHFFFAOYSA-N CPP Chemical compound OC(=O)C(C)OC1=CC=C(Cl)C=C1 DKHJWWRYTONYHB-UHFFFAOYSA-N 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
- 229940122072 Carbonic anhydrase inhibitor Drugs 0.000 description 1
- 102000000844 Cell Surface Receptors Human genes 0.000 description 1
- 108010001857 Cell Surface Receptors Proteins 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 108091006146 Channels Proteins 0.000 description 1
- 206010048650 Cholinesterase inhibition Diseases 0.000 description 1
- YAORIDZYZDUZCM-UHFFFAOYSA-N Cirazoline Chemical compound N=1CCNC=1COC1=CC=CC=C1C1CC1 YAORIDZYZDUZCM-UHFFFAOYSA-N 0.000 description 1
- 102000008130 Cyclic AMP-Dependent Protein Kinases Human genes 0.000 description 1
- 108010049894 Cyclic AMP-Dependent Protein Kinases Proteins 0.000 description 1
- MTCFGRXMJLQNBG-UWTATZPHSA-N D-Serine Chemical compound OC[C@@H](N)C(O)=O MTCFGRXMJLQNBG-UWTATZPHSA-N 0.000 description 1
- PTJADDMMFYXMMG-UHFFFAOYSA-N Demethylcitalopram Chemical compound O1CC2=CC(C#N)=CC=C2C1(CCCNC)C1=CC=C(F)C=C1 PTJADDMMFYXMMG-UHFFFAOYSA-N 0.000 description 1
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 1
- 201000010374 Down Syndrome Diseases 0.000 description 1
- NLPRAJRHRHZCQQ-UHFFFAOYSA-N Epibatidine Natural products C1=NC(Cl)=CC=C1C1C(N2)CCC2C1 NLPRAJRHRHZCQQ-UHFFFAOYSA-N 0.000 description 1
- 206010015548 Euthanasia Diseases 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 1
- 229940098788 GABA receptor antagonist Drugs 0.000 description 1
- ZXRVKCBLGJOCEE-UHFFFAOYSA-N Gaboxadol Chemical compound C1NCCC2=C1ONC2=O ZXRVKCBLGJOCEE-UHFFFAOYSA-N 0.000 description 1
- 206010017577 Gait disturbance Diseases 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 102000018899 Glutamate Receptors Human genes 0.000 description 1
- 108010027915 Glutamate Receptors Proteins 0.000 description 1
- 102000011714 Glycine Receptors Human genes 0.000 description 1
- 108010076533 Glycine Receptors Proteins 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 101000987586 Homo sapiens Eosinophil peroxidase Proteins 0.000 description 1
- 101000920686 Homo sapiens Erythropoietin Proteins 0.000 description 1
- 101000616438 Homo sapiens Microtubule-associated protein 4 Proteins 0.000 description 1
- VFIDUCMKNJIJTO-BBRMVZONSA-N ICI 118551 Chemical compound CC(C)N[C@@H](C)[C@@H](O)COC1=CC=C(C)C2=C1CCC2 VFIDUCMKNJIJTO-BBRMVZONSA-N 0.000 description 1
- 102000009032 Imidazoline Receptors Human genes 0.000 description 1
- 108010049134 Imidazoline Receptors Proteins 0.000 description 1
- MCNGUYXRBCIGOV-UHFFFAOYSA-N Immepip Chemical compound C=1N=CNC=1CC1CCNCC1 MCNGUYXRBCIGOV-UHFFFAOYSA-N 0.000 description 1
- 208000026350 Inborn Genetic disease Diseases 0.000 description 1
- MADRVGBADLFHMO-UHFFFAOYSA-N Indeloxazine Chemical compound C=1C=CC=2C=CCC=2C=1OCC1CNCCO1 MADRVGBADLFHMO-UHFFFAOYSA-N 0.000 description 1
- QZRGKCOWNLSUDK-UHFFFAOYSA-N Iodochlorine Chemical compound ICl QZRGKCOWNLSUDK-UHFFFAOYSA-N 0.000 description 1
- KRVDMABBKYMBHG-UHFFFAOYSA-N Isoguvacine Chemical compound OC(=O)C1=CCNCC1 KRVDMABBKYMBHG-UHFFFAOYSA-N 0.000 description 1
- 229940123572 Kainate receptor antagonist Drugs 0.000 description 1
- MPIZVHPMGFWKMJ-AKGZTFGVSA-N L-alpha-(methylidenecyclopropyl)glycine Chemical compound OC(=O)[C@@H](N)C1CC1=C MPIZVHPMGFWKMJ-AKGZTFGVSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- GZOVEPYOCJWRFC-UHFFFAOYSA-N L-trans-alpha-Amino-2-carboxycyclopropaneacetic acid Chemical compound OC(=O)C(N)C1CC1C(O)=O GZOVEPYOCJWRFC-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- GDBQQVLCIARPGH-UHFFFAOYSA-N Leupeptin Natural products CC(C)CC(NC(C)=O)C(=O)NC(CC(C)C)C(=O)NC(C=O)CCCN=C(N)N GDBQQVLCIARPGH-UHFFFAOYSA-N 0.000 description 1
- 208000009829 Lewy Body Disease Diseases 0.000 description 1
- 201000002832 Lewy body dementia Diseases 0.000 description 1
- 102100021794 Microtubule-associated protein 4 Human genes 0.000 description 1
- 206010028347 Muscle twitching Diseases 0.000 description 1
- GYSZUJHYXCZAKI-UHFFFAOYSA-N N-(2,3-dihydro-1,4-benzodioxin-2-ylmethyl)-2-(2,6-dimethoxyphenoxy)ethanamine Chemical compound COC1=CC=CC(OC)=C1OCCNCC1OC2=CC=CC=C2OC1 GYSZUJHYXCZAKI-UHFFFAOYSA-N 0.000 description 1
- XHLOUFPZLUULGI-UHFFFAOYSA-N N-[(4-bromophenyl)methyl]-2-(5-methoxy-1H-indol-3-yl)ethanamine Chemical compound C12=CC(OC)=CC=C2NC=C1CCNCC1=CC=C(Br)C=C1 XHLOUFPZLUULGI-UHFFFAOYSA-N 0.000 description 1
- OQFCXJDXHCDLHX-UHFFFAOYSA-N N-[5-(4,5-dihydro-1H-imidazol-2-yl)-2-hydroxy-5,6,7,8-tetrahydronaphthalen-1-yl]methanesulfonamide Chemical compound C1CCC=2C(NS(=O)(=O)C)=C(O)C=CC=2C1C1=NCCN1 OQFCXJDXHCDLHX-UHFFFAOYSA-N 0.000 description 1
- QSQQPMHPCBLLGX-UHFFFAOYSA-N N-methyl-4-[2-(phenylmethyl)phenoxy]-1-butanamine Chemical compound CNCCCCOC1=CC=CC=C1CC1=CC=CC=C1 QSQQPMHPCBLLGX-UHFFFAOYSA-N 0.000 description 1
- QQXLDOJGLXJCSE-UHFFFAOYSA-N N-methylnortropinone Natural products C1C(=O)CC2CCC1N2C QQXLDOJGLXJCSE-UHFFFAOYSA-N 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 1
- JAUOIFJMECXRGI-UHFFFAOYSA-N Neoclaritin Chemical compound C=1C(Cl)=CC=C2C=1CCC1=CC=CN=C1C2=C1CCNCC1 JAUOIFJMECXRGI-UHFFFAOYSA-N 0.000 description 1
- MTXSIJUGVMTTMU-UHFFFAOYSA-N Neonicotine Natural products N1CCCCC1C1=CC=CN=C1 MTXSIJUGVMTTMU-UHFFFAOYSA-N 0.000 description 1
- DLHLOYYQQGSXCC-DOFZRALJSA-N O-Arachidonoyl ethanolamine Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(=O)OCCN DLHLOYYQQGSXCC-DOFZRALJSA-N 0.000 description 1
- QHGUCRYDKWKLMG-MRVPVSSYSA-N Octopamine Natural products NC[C@@H](O)C1=CC=C(O)C=C1 QHGUCRYDKWKLMG-MRVPVSSYSA-N 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 229920005439 Perspex® Polymers 0.000 description 1
- DYUQAZSOFZSPHD-UHFFFAOYSA-N Phenylpropyl alcohol Natural products CCC(O)C1=CC=CC=C1 DYUQAZSOFZSPHD-UHFFFAOYSA-N 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 206010036049 Polycystic ovaries Diseases 0.000 description 1
- 206010062519 Poor quality sleep Diseases 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 102000003923 Protein Kinase C Human genes 0.000 description 1
- 108090000315 Protein Kinase C Proteins 0.000 description 1
- QIZDQFOVGFDBKW-DHBOJHSNSA-N Pseudotropine Natural products OC1C[C@@H]2[N+](C)[C@H](C1)CC2 QIZDQFOVGFDBKW-DHBOJHSNSA-N 0.000 description 1
- KDCGOANMDULRCW-UHFFFAOYSA-N Purine Natural products N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- XSVMFMHYUFZWBK-NSHDSACASA-N Rivastigmine Chemical compound CCN(C)C(=O)OC1=CC=CC([C@H](C)N(C)C)=C1 XSVMFMHYUFZWBK-NSHDSACASA-N 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- LPMRCCNDNGONCD-RITPCOANSA-N Selfotel Chemical compound OC(=O)[C@@H]1C[C@H](CP(O)(O)=O)CCN1 LPMRCCNDNGONCD-RITPCOANSA-N 0.000 description 1
- 108010052164 Sodium Channels Proteins 0.000 description 1
- 102000018674 Sodium Channels Human genes 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- FKNQFGJONOIPTF-UHFFFAOYSA-N Sodium cation Chemical compound [Na+] FKNQFGJONOIPTF-UHFFFAOYSA-N 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 239000005864 Sulphur Substances 0.000 description 1
- 206010042674 Swelling Diseases 0.000 description 1
- 206010044565 Tremor Diseases 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
- 206010044688 Trisomy 21 Diseases 0.000 description 1
- 102000014384 Type C Phospholipases Human genes 0.000 description 1
- 108010079194 Type C Phospholipases Proteins 0.000 description 1
- 102000006275 Ubiquitin-Protein Ligases Human genes 0.000 description 1
- 108010083111 Ubiquitin-Protein Ligases Proteins 0.000 description 1
- DXPOSRCHIDYWHW-UHFFFAOYSA-N Xamoterol Chemical compound C=1C=C(O)C=CC=1OCC(O)CNCCNC(=O)N1CCOCC1 DXPOSRCHIDYWHW-UHFFFAOYSA-N 0.000 description 1
- ZODSPDOOCZZEIM-BBRMVZONSA-N [(2S)-3-[[(1S)-1-(3,4-dichlorophenyl)ethyl]amino]-2-hydroxypropyl]-(phenylmethyl)phosphinic acid Chemical compound C([C@@H](O)CN[C@@H](C)C=1C=C(Cl)C(Cl)=CC=1)P(O)(=O)CC1=CC=CC=C1 ZODSPDOOCZZEIM-BBRMVZONSA-N 0.000 description 1
- OKDOWCKDTWNRCB-GQCTYLIASA-N [(e)-4-amino-5-ethoxy-2-methyl-5-oxopent-2-enyl]phosphonic acid Chemical compound CCOC(=O)C(N)\C=C(/C)CP(O)(O)=O OKDOWCKDTWNRCB-GQCTYLIASA-N 0.000 description 1
- UOHUDFHWFDUDID-UHFFFAOYSA-N [Cl].C[SiH](C)C Chemical compound [Cl].C[SiH](C)C UOHUDFHWFDUDID-UHFFFAOYSA-N 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 239000012445 acidic reagent Substances 0.000 description 1
- 239000007825 activation reagent Substances 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- KTEBZVJGMARTOQ-GCJKJVERSA-N adrogolide Chemical compound CC(=O)OC1=C(OC(C)=O)C=C2[C@H]3C(C=C(S4)CCC)=C4CN[C@@H]3CCC2=C1 KTEBZVJGMARTOQ-GCJKJVERSA-N 0.000 description 1
- 229950007871 adrogolide Drugs 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 229960004343 alendronic acid Drugs 0.000 description 1
- 230000036626 alertness Effects 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 230000003281 allosteric effect Effects 0.000 description 1
- LYPCGXKCQDYTFV-UHFFFAOYSA-N alpha-methylserotonin Chemical compound C1=C(O)C=C2C(CC(N)C)=CNC2=C1 LYPCGXKCQDYTFV-UHFFFAOYSA-N 0.000 description 1
- 229960003805 amantadine Drugs 0.000 description 1
- 229960002749 aminolevulinic acid Drugs 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 229930014345 anabasine Natural products 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 229950000969 anpirtoline Drugs 0.000 description 1
- 125000005428 anthryl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C3C(*)=C([H])C([H])=C([H])C3=C([H])C2=C1[H] 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- SDNYTAYICBFYFH-TUFLPTIASA-N antipain Chemical compound NC(N)=NCCC[C@@H](C=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 SDNYTAYICBFYFH-TUFLPTIASA-N 0.000 description 1
- 239000003420 antiserotonin agent Substances 0.000 description 1
- 229960004405 aprotinin Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 235000009697 arginine Nutrition 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 101150088806 atpA gene Proteins 0.000 description 1
- 230000002567 autonomic effect Effects 0.000 description 1
- 125000005334 azaindolyl group Chemical group N1N=C(C2=CC=CC=C12)* 0.000 description 1
- 150000003851 azoles Chemical class 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000003542 behavioural effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- QRUDEWIWKLJBPS-UHFFFAOYSA-N benzotriazole Chemical compound C1=CC=C2N[N][N]C2=C1 QRUDEWIWKLJBPS-UHFFFAOYSA-N 0.000 description 1
- 239000012964 benzotriazole Substances 0.000 description 1
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 102000012740 beta Adrenergic Receptors Human genes 0.000 description 1
- 108010079452 beta Adrenergic Receptors Proteins 0.000 description 1
- 229960004933 bifemelane Drugs 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 229920001400 block copolymer Polymers 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 210000001218 blood-brain barrier Anatomy 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- SGOFAUSEYBZKDQ-UHFFFAOYSA-N brl-44408 Chemical compound C1C2=CC=CC=C2C(C)N1CC1=NCCN1 SGOFAUSEYBZKDQ-UHFFFAOYSA-N 0.000 description 1
- WZXHSWVDAYOFPE-UHFFFAOYSA-N brofaromine Chemical compound C=1C2=CC(OC)=CC(Br)=C2OC=1C1CCNCC1 WZXHSWVDAYOFPE-UHFFFAOYSA-N 0.000 description 1
- 229950004068 brofaromine Drugs 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 235000011089 carbon dioxide Nutrition 0.000 description 1
- 239000003489 carbonate dehydratase inhibitor Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 239000006143 cell culture medium Substances 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- QIIVUOWTHWIXFO-UHFFFAOYSA-N cgp-35348 Chemical compound CCOC(OCC)P(O)(=O)CCCN QIIVUOWTHWIXFO-UHFFFAOYSA-N 0.000 description 1
- BDYHNCZIGYIOGJ-XWCPEMDWSA-N cgp-37849 Chemical compound OP(=O)(O)CC(/C)=C/[C@@H](N)C(O)=O BDYHNCZIGYIOGJ-XWCPEMDWSA-N 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 229950008137 cirazoline Drugs 0.000 description 1
- 229960001117 clenbuterol Drugs 0.000 description 1
- STJMRWALKKWQGH-UHFFFAOYSA-N clenbuterol Chemical compound CC(C)(C)NCC(O)C1=CC(Cl)=C(N)C(Cl)=C1 STJMRWALKKWQGH-UHFFFAOYSA-N 0.000 description 1
- 229960002896 clonidine Drugs 0.000 description 1
- 230000003930 cognitive ability Effects 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- JGGVBBYJRQOPPA-BBRMVZONSA-N cyclohexylmethyl-[(2s)-3-[[(1s)-1-(3,4-dichlorophenyl)ethyl]amino]-2-hydroxypropyl]phosphinic acid Chemical compound C([C@@H](O)CN[C@@H](C)C=1C=C(Cl)C(Cl)=CC=1)P(O)(=O)CC1CCCCC1 JGGVBBYJRQOPPA-BBRMVZONSA-N 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- MATPZHBYOVDBLI-JJYYJPOSSA-N dcg-iv Chemical compound OC(=O)[C@@H](N)C1[C@@H](C(O)=O)[C@@H]1C(O)=O MATPZHBYOVDBLI-JJYYJPOSSA-N 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 229960001271 desloratadine Drugs 0.000 description 1
- SRPXSILJHWNFMK-ZBEGNZNMSA-N desmethylsertraline Chemical compound C1([C@@H]2CC[C@@H](C3=CC=CC=C32)N)=CC=C(Cl)C(Cl)=C1 SRPXSILJHWNFMK-ZBEGNZNMSA-N 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- HESHRHUZIWVEAJ-JGRZULCMSA-N dihydroergotamine Chemical compound C([C@H]1C(=O)N2CCC[C@H]2[C@]2(O)O[C@@](C(N21)=O)(C)NC(=O)[C@H]1CN([C@H]2[C@@H](C3=CC=CC4=NC=C([C]34)C2)C1)C)C1=CC=CC=C1 HESHRHUZIWVEAJ-JGRZULCMSA-N 0.000 description 1
- 229960004704 dihydroergotamine Drugs 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- OBISXEJSEGNNKL-UHFFFAOYSA-N dinitrogen-n-sulfide Chemical compound [N-]=[N+]=S OBISXEJSEGNNKL-UHFFFAOYSA-N 0.000 description 1
- OCUJLLGVOUDECM-UHFFFAOYSA-N dipivefrin Chemical compound CNCC(O)C1=CC=C(OC(=O)C(C)(C)C)C(OC(=O)C(C)(C)C)=C1 OCUJLLGVOUDECM-UHFFFAOYSA-N 0.000 description 1
- 229960000966 dipivefrine Drugs 0.000 description 1
- QLTXKCWMEZIHBJ-PJGJYSAQSA-N dizocilpine maleate Chemical compound OC(=O)\C=C/C(O)=O.C12=CC=CC=C2[C@]2(C)C3=CC=CC=C3C[C@H]1N2 QLTXKCWMEZIHBJ-PJGJYSAQSA-N 0.000 description 1
- VZFRNCSOCOPNDB-AJKFJWDBSA-N domoic acid Chemical compound OC(=O)[C@@H](C)\C=C\C=C(/C)[C@H]1CN[C@H](C(O)=O)[C@H]1CC(O)=O VZFRNCSOCOPNDB-AJKFJWDBSA-N 0.000 description 1
- VZFRNCSOCOPNDB-UHFFFAOYSA-N domoic acid Natural products OC(=O)C(C)C=CC=C(C)C1CNC(C(O)=O)C1CC(O)=O VZFRNCSOCOPNDB-UHFFFAOYSA-N 0.000 description 1
- 229960003638 dopamine Drugs 0.000 description 1
- 229940052760 dopamine agonists Drugs 0.000 description 1
- 239000003136 dopamine receptor stimulating agent Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- QFYBYZLHPIALCZ-ZETCQYMHSA-N eglu Chemical compound CC[C@@](N)(C(O)=O)CCC(O)=O QFYBYZLHPIALCZ-ZETCQYMHSA-N 0.000 description 1
- 230000005611 electricity Effects 0.000 description 1
- 238000003372 electrophysiological method Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- NLPRAJRHRHZCQQ-IVZWLZJFSA-N epibatidine Chemical compound C1=NC(Cl)=CC=C1[C@@H]1[C@H](N2)CC[C@H]2C1 NLPRAJRHRHZCQQ-IVZWLZJFSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 229960004979 fampridine Drugs 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229960002949 fluorouracil Drugs 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 230000003371 gabaergic effect Effects 0.000 description 1
- 230000005021 gait Effects 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 210000004051 gastric juice Anatomy 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 208000016361 genetic disease Diseases 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 229960002743 glutamine Drugs 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 229960002449 glycine Drugs 0.000 description 1
- 125000004438 haloalkoxy group Chemical group 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 210000003677 hemocyte Anatomy 0.000 description 1
- 229940000351 hemocyte Drugs 0.000 description 1
- 102000044890 human EPO Human genes 0.000 description 1
- 150000002430 hydrocarbons Chemical group 0.000 description 1
- QLZLBYYNMGQIAR-UHFFFAOYSA-N hydron;3-piperidin-1-ylpropyl 4-amino-5-chloro-2-methoxybenzoate;chloride Chemical compound Cl.COC1=CC(N)=C(Cl)C=C1C(=O)OCCCN1CCCCC1 QLZLBYYNMGQIAR-UHFFFAOYSA-N 0.000 description 1
- 238000005286 illumination Methods 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- MNLULKBKWKTZPE-UHFFFAOYSA-N indantadol Chemical compound C1=CC=C2CC(NCC(=O)N)CC2=C1 MNLULKBKWKTZPE-UHFFFAOYSA-N 0.000 description 1
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 229960004333 indeloxazine Drugs 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 230000010365 information processing Effects 0.000 description 1
- ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 description 1
- 238000013101 initial test Methods 0.000 description 1
- 239000003999 initiator Substances 0.000 description 1
- CDAISMWEOUEBRE-UHFFFAOYSA-N inositol Chemical compound OC1C(O)C(O)C(O)C(O)C1O CDAISMWEOUEBRE-UHFFFAOYSA-N 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 230000000622 irritating effect Effects 0.000 description 1
- VZFRNCSOCOPNDB-OXYNIABMSA-N isodomoic acid D Natural products CC(C=C/C=C(/C)C1CNC(C1CC(=O)O)C(=O)O)C(=O)O VZFRNCSOCOPNDB-OXYNIABMSA-N 0.000 description 1
- 125000005956 isoquinolyl group Chemical group 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- RPCVIAXDAUMJJP-PZBABLGHSA-N ispronicline Chemical compound CN[C@@H](C)C\C=C\C1=CN=CC(OC(C)C)=C1 RPCVIAXDAUMJJP-PZBABLGHSA-N 0.000 description 1
- 239000002909 kainic acid receptor agonist Substances 0.000 description 1
- 239000002873 kainic acid receptor antagonist Substances 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 230000008449 language Effects 0.000 description 1
- 229950005862 lazabemide Drugs 0.000 description 1
- GDBQQVLCIARPGH-ULQDDVLXSA-N leupeptin Chemical compound CC(C)C[C@H](NC(C)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C=O)CCCN=C(N)N GDBQQVLCIARPGH-ULQDDVLXSA-N 0.000 description 1
- 108010052968 leupeptin Proteins 0.000 description 1
- 210000000088 lip Anatomy 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- STIRHCNEGQQBOY-QEYWKRMJSA-N ly-235,959 Chemical compound C1[C@@H](CP(O)(O)=O)CC[C@H]2CN[C@H](C(=O)O)C[C@H]21 STIRHCNEGQQBOY-QEYWKRMJSA-N 0.000 description 1
- DWLOVDOPFJPWNE-HKUYNNGSSA-N ly-307,452 Chemical compound C=1C=CC=CC=1C(CCC[C@@H](C[C@H](N)C(O)=O)C(O)=O)C1=CC=CC=C1 DWLOVDOPFJPWNE-HKUYNNGSSA-N 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- QSLMDECMDJKHMQ-GSXCWMCISA-N maprotiline Chemical compound C12=CC=CC=C2[C@@]2(CCCNC)C3=CC=CC=C3[C@@H]1CC2 QSLMDECMDJKHMQ-GSXCWMCISA-N 0.000 description 1
- 229960004090 maprotiline Drugs 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- BUGYDGFZZOZRHP-UHFFFAOYSA-N memantine Chemical compound C1C(C2)CC3(C)CC1(C)CC2(N)C3 BUGYDGFZZOZRHP-UHFFFAOYSA-N 0.000 description 1
- 229960004640 memantine Drugs 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000007087 memory ability Effects 0.000 description 1
- 230000009225 memory damage Effects 0.000 description 1
- 230000006386 memory function Effects 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- MFUKVPOVVKKLRQ-UHFFFAOYSA-N methyl(1,2,3,6-tetrahydropyridin-1-ium-4-yl)phosphinate Chemical compound CP(O)(=O)C1=CCNCC1 MFUKVPOVVKKLRQ-UHFFFAOYSA-N 0.000 description 1
- 229950000928 milacemide Drugs 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- LDMWSLGGVTVJPG-UHFFFAOYSA-N minaprine Chemical compound CC1=CC(C=2C=CC=CC=2)=NN=C1NCCN1CCOCC1 LDMWSLGGVTVJPG-UHFFFAOYSA-N 0.000 description 1
- 229960004758 minaprine Drugs 0.000 description 1
- 229940101972 mirapex Drugs 0.000 description 1
- JLESVLCTIOAHPT-UHFFFAOYSA-N mmai Chemical compound C1=C(C)C(OC)=CC2=C1CC(N)C2 JLESVLCTIOAHPT-UHFFFAOYSA-N 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 229950010854 mofegiline Drugs 0.000 description 1
- 206010028417 myasthenia gravis Diseases 0.000 description 1
- SCKBPXUWGMKLDM-UHFFFAOYSA-N n-(2-aminoethyl)-5-(3-fluorophenyl)-1,3-thiazole-4-carboxamide Chemical compound N1=CSC(C=2C=C(F)C=CC=2)=C1C(=O)NCCN SCKBPXUWGMKLDM-UHFFFAOYSA-N 0.000 description 1
- JZXRLKWWVNUZRB-UHFFFAOYSA-N n-(2-aminoethyl)-5-chloropyridine-2-carboxamide Chemical compound NCCNC(=O)C1=CC=C(Cl)C=N1 JZXRLKWWVNUZRB-UHFFFAOYSA-N 0.000 description 1
- ATKZKAYWARYLBW-UHFFFAOYSA-N n-(3,5-dichloro-2-methoxyphenyl)-4-methoxy-3-piperazin-1-ylbenzenesulfonamide Chemical compound COC1=CC=C(S(=O)(=O)NC=2C(=C(Cl)C=C(Cl)C=2)OC)C=C1N1CCNCC1 ATKZKAYWARYLBW-UHFFFAOYSA-N 0.000 description 1
- RPCVIAXDAUMJJP-UHFFFAOYSA-N n-methyl-5-(5-propan-2-yloxypyridin-3-yl)pent-4-en-2-amine Chemical compound CNC(C)CC=CC1=CN=CC(OC(C)C)=C1 RPCVIAXDAUMJJP-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 208000004296 neuralgia Diseases 0.000 description 1
- 230000003955 neuronal function Effects 0.000 description 1
- 208000021722 neuropathic pain Diseases 0.000 description 1
- 230000000324 neuroprotective effect Effects 0.000 description 1
- 239000003367 nicotinic antagonist Substances 0.000 description 1
- ITJNARMNRKSWTA-UHFFFAOYSA-N nisoxetine Chemical compound C=1C=CC=CC=1C(CCNC)OC1=CC=CC=C1OC ITJNARMNRKSWTA-UHFFFAOYSA-N 0.000 description 1
- 125000006574 non-aromatic ring group Chemical group 0.000 description 1
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 1
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
- 238000010606 normalization Methods 0.000 description 1
- 229960001576 octopamine Drugs 0.000 description 1
- 229920002113 octoxynol Polymers 0.000 description 1
- 201000005111 ocular hyperemia Diseases 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 150000004866 oxadiazoles Chemical class 0.000 description 1
- FDXQKWSTUZCCTM-UHFFFAOYSA-N oxaprotiline Chemical compound C12=CC=CC=C2C2(CC(O)CNC)C3=CC=CC=C3C1CC2 FDXQKWSTUZCCTM-UHFFFAOYSA-N 0.000 description 1
- 229960001528 oxymetazoline Drugs 0.000 description 1
- 210000005034 parasympathetic neuron Anatomy 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 238000011302 passive avoidance test Methods 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 229950000964 pepstatin Drugs 0.000 description 1
- 108010091212 pepstatin Proteins 0.000 description 1
- FAXGPCHRFPCXOO-LXTPJMTPSA-N pepstatin A Chemical compound OC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)NC(=O)CC(C)C FAXGPCHRFPCXOO-LXTPJMTPSA-N 0.000 description 1
- 208000027232 peripheral nervous system disease Diseases 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- VSGNGLJPOGUDON-UHFFFAOYSA-N phaclofen Chemical compound OP(=O)(O)CC(CN)C1=CC=C(Cl)C=C1 VSGNGLJPOGUDON-UHFFFAOYSA-N 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- UEXCJVNBTNXOEH-UHFFFAOYSA-N phenyl acethylene Natural products C#CC1=CC=CC=C1 UEXCJVNBTNXOEH-UHFFFAOYSA-N 0.000 description 1
- PWXJULSLLONQHY-UHFFFAOYSA-N phenylcarbamic acid Chemical class OC(=O)NC1=CC=CC=C1 PWXJULSLLONQHY-UHFFFAOYSA-N 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 229960005141 piperazine Drugs 0.000 description 1
- 239000004417 polycarbonate Substances 0.000 description 1
- 229920000515 polycarbonate Polymers 0.000 description 1
- 201000010065 polycystic ovary syndrome Diseases 0.000 description 1
- 239000004926 polymethyl methacrylate Substances 0.000 description 1
- 229920006316 polyvinylpyrrolidine Polymers 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 238000011533 pre-incubation Methods 0.000 description 1
- 229960001233 pregabalin Drugs 0.000 description 1
- 230000003518 presynaptic effect Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 208000037920 primary disease Diseases 0.000 description 1
- FKNXQNWAXFXVNW-BLLLJJGKSA-N procaterol Chemical compound N1C(=O)C=CC2=C1C(O)=CC=C2[C@@H](O)[C@@H](NC(C)C)CC FKNXQNWAXFXVNW-BLLLJJGKSA-N 0.000 description 1
- 229960002288 procaterol Drugs 0.000 description 1
- 238000004886 process control Methods 0.000 description 1
- 235000013772 propylene glycol Nutrition 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 229960001509 protriptyline hydrochloride Drugs 0.000 description 1
- 235000019633 pungent taste Nutrition 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 238000013139 quantization Methods 0.000 description 1
- XRXDAJYKGWNHTQ-UHFFFAOYSA-N quipazine Chemical compound C1CNCCN1C1=CC=C(C=CC=C2)C2=N1 XRXDAJYKGWNHTQ-UHFFFAOYSA-N 0.000 description 1
- 229950002315 quipazine Drugs 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- RUOKEQAAGRXIBM-GFCCVEGCSA-N rasagiline Chemical compound C1=CC=C2[C@H](NCC#C)CCC2=C1 RUOKEQAAGRXIBM-GFCCVEGCSA-N 0.000 description 1
- 229960000245 rasagiline Drugs 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- CBQGYUDMJHNJBX-RTBURBONSA-N reboxetine Chemical compound CCOC1=CC=CC=C1O[C@H](C=1C=CC=CC=1)[C@@H]1OCCNC1 CBQGYUDMJHNJBX-RTBURBONSA-N 0.000 description 1
- 229960003770 reboxetine Drugs 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 229950004933 rimcazole Drugs 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- JUOSGGQXEBBCJB-GORDUTHDSA-N rivanicline Chemical compound CNCC\C=C\C1=CC=CN=C1 JUOSGGQXEBBCJB-GORDUTHDSA-N 0.000 description 1
- 229960004136 rivastigmine Drugs 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- SEYCKMQSPUVYEF-LURJTMIESA-N sch-50911 Chemical compound CC1(C)CO[C@@H](CC(O)=O)CN1 SEYCKMQSPUVYEF-LURJTMIESA-N 0.000 description 1
- MDJYHWLDDJBTMX-UHFFFAOYSA-N sdb-001 Chemical compound C12=CC=CC=C2N(CCCCC)C=C1C(=O)NC1(C2)CC(C3)CC2CC3C1 MDJYHWLDDJBTMX-UHFFFAOYSA-N 0.000 description 1
- 229930000044 secondary metabolite Natural products 0.000 description 1
- 229940076279 serotonin Drugs 0.000 description 1
- 239000000952 serotonin receptor agonist Substances 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- NHVRIDDXGZPJTJ-UHFFFAOYSA-N skf-97,541 Chemical compound CP(O)(=O)CCCN NHVRIDDXGZPJTJ-UHFFFAOYSA-N 0.000 description 1
- 230000000391 smoking effect Effects 0.000 description 1
- 229910001415 sodium ion Inorganic materials 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- XFOHHIYSRDUSCX-UHFFFAOYSA-M sodium;5-[[4-[2-[methyl(pyridin-2-yl)amino]ethoxy]phenyl]methyl]-1,3-thiazolidin-3-ide-2,4-dione Chemical compound [Na+].C=1C=CC=NC=1N(C)CCOC(C=C1)=CC=C1CC1SC(=O)[N-]C1=O XFOHHIYSRDUSCX-UHFFFAOYSA-M 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- GUCKKCMJTSNWCU-BQBZGAKWSA-N spaglumic acid Chemical compound CC(=O)N[C@H](C(O)=O)CC(=O)N[C@H](C(O)=O)CCC(O)=O GUCKKCMJTSNWCU-BQBZGAKWSA-N 0.000 description 1
- 229960000341 spaglumic acid Drugs 0.000 description 1
- 229940063673 spermidine Drugs 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 238000012453 sprague-dawley rat model Methods 0.000 description 1
- 230000003068 static effect Effects 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 230000002889 sympathetic effect Effects 0.000 description 1
- 230000016978 synaptic transmission, cholinergic Effects 0.000 description 1
- 230000015883 synaptic transmission, dopaminergic Effects 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 229950007352 talopram Drugs 0.000 description 1
- LJBBMCNHIUJBDU-UHFFFAOYSA-N talopram Chemical compound O1C(C)(C)C2=CC=CC=C2C1(CCCNC)C1=CC=CC=C1 LJBBMCNHIUJBDU-UHFFFAOYSA-N 0.000 description 1
- 229950002139 talsupram Drugs 0.000 description 1
- 229960000195 terbutaline Drugs 0.000 description 1
- NDSGWNVNYIVEKU-UHFFFAOYSA-N tetrindole hydrochloride Chemical compound Cl.C1CCCCC1C1=CC=C(N2C3=C4CCCC3NCC2)C4=C1 NDSGWNVNYIVEKU-UHFFFAOYSA-N 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 229960003053 thiamphenicol Drugs 0.000 description 1
- OTVAEFIXJLOWRX-NXEZZACHSA-N thiamphenicol Chemical compound CS(=O)(=O)C1=CC=C([C@@H](O)[C@@H](CO)NC(=O)C(Cl)Cl)C=C1 OTVAEFIXJLOWRX-NXEZZACHSA-N 0.000 description 1
- AMGKHLVPQHMHGQ-ZYHUDNBSSA-N thiamphenicol glycinate Chemical compound CS(=O)(=O)C1=CC=C([C@@H](O)[C@@H](COC(=O)CN)NC(=O)C(Cl)Cl)C=C1 AMGKHLVPQHMHGQ-ZYHUDNBSSA-N 0.000 description 1
- 229960002355 thiamphenicol glycinate Drugs 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 229950002859 tracazolate Drugs 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- 229940048102 triphosphoric acid Drugs 0.000 description 1
- CYHOMWAPJJPNMW-JIGDXULJSA-N tropine Chemical group C1[C@@H](O)C[C@H]2CC[C@@H]1N2C CYHOMWAPJJPNMW-JIGDXULJSA-N 0.000 description 1
- WVPSKSLAZQPAKQ-CDMJZVDBSA-N trovafloxacin Chemical compound C([C@H]1[C@@H]([C@H]1C1)N)N1C(C(=CC=1C(=O)C(C(O)=O)=C2)F)=NC=1N2C1=CC=C(F)C=C1F WVPSKSLAZQPAKQ-CDMJZVDBSA-N 0.000 description 1
- 229960001005 tuberculin Drugs 0.000 description 1
- 229950009811 ubenimex Drugs 0.000 description 1
- 150000003672 ureas Chemical class 0.000 description 1
- 229940005605 valeric acid Drugs 0.000 description 1
- 229960001255 viloxazine Drugs 0.000 description 1
- 210000001835 viscera Anatomy 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 230000001755 vocal effect Effects 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 230000003936 working memory Effects 0.000 description 1
- 229960004928 xamoterol Drugs 0.000 description 1
- 108010015889 zeta receptor Proteins 0.000 description 1
- 229940124629 β-receptor antagonist Drugs 0.000 description 1
Images
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
A kind ofly can suppress cholinesterase activity, and discharge a kind of compound of pharmacological activity reagent by hydrolysis.The described pharmacological activity reagent that hydrolysis by described compound obtains can be treated, neurological conditions for example, cholinergic disappearance and illness or the disease relevant with the disappearance of pharmacological activity reagent, described pharmacological activity reagent are vagusstoffs for example.
Description
Related application
The application requires to enjoy U.S. Patent application No.60/899,111 and No.60/959,901 rights and interests and right of priority, the former applying date is on February 2nd, 2007, the latter's the applying date is on July 16th, 2007, and the disclosed content of above-mentioned application is hereby incorporated by.
Background technology
The interruption that human many illnesss and disease all are accompanied by the cell signal molecule, or the resulting result of the interruption of cell signal molecule.For example, described cell signal molecule may take place unsuitable synthetic, discharge or absorb again, perhaps acceptor matrix or non-acceptor matrix may be interrupted the mediation to the cell signal of described molecule, thereby produce disease or other illnesss.In many situations, clinical processing scheme and current utilizable medicine are usually relevant with the intravital side effect of patient and must carry out cautious monitoring to it.Those treatments are accompanied by the interruption of cell signal molecule or the current strategies of the research and development of the medicine of the result's of interrupting as the cell signal molecule illness and disease need be carried out the active modification of important structure to compound.In addition, current utilizable medicine can not be directed to specific cell or tissue with described medicine usually, thereby can not carry out sending of medicine with a kind of long-term effect that continues.In many cases, the symptom of described disease or illness can not be effectively treated in the correction of carrying out for the interruption of individual cells signaling molecule.Therefore, need research and development a kind of new, improved and effectively treat the method for disease or illness, wherein said disease or illness are relevant with the interruption of cell signal molecule, perhaps are accompanied by the interruption of cell signal molecule and produce.
Summary of the invention
This bright (Stigmine) is a kind of acetylcholinesterase depressant based on carbaminate.Acetylcholinesterase depressant can strengthen cognitive function by the cholinergic function that strengthens brain, and for example, this is proved by the methods of treatment of Alzheimer's disease.Alzheimer's disease patient shows other symptom usually, comprise dejected, anxiety and somnopathy, all these symptoms can be improved by the treatment of using acetylcholinesterase depressant, and wherein said acetylcholinesterase depressant is bright (rivastigmine) and the Physostigmine of for example Li Wasi.
The bright Physostigmine of sharp gas
In animal model, acetylcholinesterase depressant shows the lenitive effect equally.Therefore the compound of inferior class (thefollowing classes) product that mixes the bright or Physostigmine and the described medicine of favourable gas can provide additional or collaborative treatment effect for the patient, for example, described patient suffers from Alzheimer's disease, Parkinson's disease, glaucoma, the tumour illness, perhaps delayed gastric emptying, or suffer from and note damaged many moving obstacles (ADHD), phobia, apoplexy, multiple sclerosis, somnopathy, insane, pain, anticholinergic agents is excessive, the perhaps patient that relies on of tobacco, that is, the patient who attempts to give up smoking is used described compound.
The present invention relates to have the compound of cholinesterase inhibition.The invention still further relates to the method for use above-claimed cpd and the pharmaceutical composition of described compound.
In one aspect, the present invention includes a kind of according to the compound shown in formula I or the formula II:
Or the acceptable salt of the medicine of this compound, wherein Q is selected from the structural formula shown in the table 1; R
1Be selected from hydrogen, unsubstituted alkyl, substituted alkyl, unsubstituted aralkyl, substituted aralkyl, unsubstituted iso-alkyl, and substituted iso-alkyl or R
1It is dead key; R
3, R
4And R
5Independently be selected from unsubstituted alkyl and hydrogen respectively separately.
In one embodiment, the present invention is a kind of according to the compound shown in the formula I.In another embodiment, the present invention is a kind of according to the compound shown in the formula II.
In one embodiment, the present invention is a kind of according to the compound shown in formula I or the formula II, wherein R
3, R
4And R
5In at least one be unsubstituted alkyl.In another embodiment, the present invention is a kind of compound, wherein R
3, R
4And R
5In at least two be unsubstituted alkyl.In another embodiment, the present invention is a kind of compound, wherein R
3, R
4And R
5All are unsubstituted alkyl.In one embodiment, the present invention is a kind of aforesaid compound, and wherein unsubstituted alkyl is a methyl.
In one embodiment, the present invention is a kind of compound, wherein R
1It is dead key.In one embodiment, R
1Be selected from hydrogen, substituted and unsubstituted alkyl.In another embodiment, R
1Be selected from hydrogen and unsubstituted alkyl.In one embodiment, R
1Be selected from methyl, hydrogen, ethyl, butyl, sec.-propyl, propyl group, and the tertiary butyl.In another embodiment, R
1Be hydrogen.In another embodiment, R
1It is unsubstituted alkyl.In one embodiment, R
1It is branched-chain alkyl.In one embodiment, R
1It is straight chained alkyl.In another embodiment, R
1Be selected from the sec.-propyl and the tertiary butyl.In one embodiment, R
1Be selected from methyl, ethyl, propyl group, and butyl.In one embodiment, R
1It is methyl.In one embodiment, R
1Be hydrogen or methyl.
In one embodiment, the present invention is a kind of compound, and wherein Q is selected from P, S, R, Z, Y, SS, JJJ, YY, EEE, UU, AA, FFF, CCC, U, T, X, V, P, Q ', U, BB, CC, DD, SSS, TTT, MM, UU, and XX.In another embodiment, Q is selected from X, V, P, Q ', U, R, S, Y, T, Z, AA, BB, CC, DD, SSS, TTT, MM, UU, and XX.In one embodiment, Q is not R, NNN, QQQ, 2L, 2M, and 2PP.In another embodiment, Q is not EE.In another embodiment, Q is not a kind of amphetamines compound.
In one embodiment, the present invention is a kind of compound, and described compound is selected from compound 2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30, and 31.In another embodiment, described compound is selected from compounds X, V, P, Q ', U, R, S, Y, T, Z, AA, BB, CC, DD, SSS, TTT, MM, UU, and XX.
In one embodiment, the present invention is a kind of pharmaceutical composition, and described pharmaceutical composition comprises the acceptable salt of the medicine of compound of the present invention or this compound.In another embodiment, the present invention is a kind of pharmaceutical composition, and described pharmaceutical composition comprises the acceptable salt of medicine and a kind of vehicle of compound of the present invention or this compound.
In one embodiment, the present invention includes a kind of method that individuality is treated, wherein said individuality suffers from the illness relevant with the activity of acetylcholinesterase, described method is treated by means from compound of the present invention to described individuality that use, and wherein said compound can acetylcholine esterase inhibition.The present invention includes compound of the present invention and be used at individuality the application in the medicine of the illness relevant with the activity of acetylcholinesterase in preparation, wherein said compound can acetylcholine esterase inhibition.In one embodiment, the present invention includes a kind of method that individuality is treated, wherein said individuality suffers from the illness relevant with the activity of acetylcholinesterase, described method is by using compounds for treating of the present invention to described individuality, wherein said illness is selected from central nervous system disorders, peripheral nervous system illness and disorder of autonomic nervous system.The present invention includes compound of the present invention and be used for application in the medicine that individuality is treated the illness relevant with the activity of acetylcholinesterase in preparation, wherein, described illness is selected from central nervous system disorders, peripheral nervous system illness and disorder of autonomic nervous system.In one embodiment, described central nervous system disorders is selected from the group of being made up of following disease: Parkinson's disease, memory injury and cognitive function damage.In another embodiment, described memory injury is to occur in the philtrum relevant with the illness that is selected from following disease: Alzheimer's disease, the lethe relevant with the age, memory is consolidated the damage of aspect, the damage of short-term memory aspect, mild cognitive function damage and multiple sclerosis.
In one embodiment, the present invention includes a kind of method that increases individual vagusstoff, described method is finished by using compound of the present invention to described individuality, and wherein said compound can suppress Pseudocholinesterase, thereby increases vagusstoff.The present invention includes a kind of manufacture method of pharmaceutical preparation, described pharmaceutical preparation can increase individual vagusstoff, and wherein said compound can suppress Pseudocholinesterase, thereby increases vagusstoff.
In one embodiment, the present invention includes a kind of method for the treatment of individual cholinergic disappearance, described method is finished by using compound of the present invention to described individuality, treats cholinergic disappearance in the described individuality thereby wherein said compound can suppress Pseudocholinesterase.The present invention includes compound of the present invention and be used for the treatment of application in the medicine of individual cholinergic disappearance, treat cholinergic disappearance in the described individuality thereby wherein said compound can suppress Pseudocholinesterase in preparation.In one embodiment, described cholinergic disappearance is an Alzheimer's disease.In another embodiment, described cholinergic disappearance is an Alzheimer's disease.
In one embodiment, the present invention includes a kind of method for the treatment of individual memory injury, described method is finished by using compound of the present invention to described individuality, thereby wherein said compound can suppress the memory injury that Pseudocholinesterase is treated described individuality.The present invention includes compound of the present invention and be used to make the purposes of pharmaceutical preparation, wherein said pharmaceutical preparation is used for the treatment of individual memory injury, thereby wherein said compound can suppress the memory injury that Pseudocholinesterase is treated described individuality.In one embodiment, the memory injury of the individuality that the present invention is included is selected from the damage that the aspect is consolidated in memory, the damage of the damage of long-term memory aspect and short-term memory aspect.In another embodiment, described memory injury is relevant with the illness that is selected from following disease: Alzheimer's disease, the lethe relevant with the age, mild cognitive function damage and multiple sclerosis.
In one embodiment, the present invention includes the method for a kind of treatment illness relevant with the activity of the acetylcholinesterase of individuality, described method is finished by using compound of the present invention, wherein said illness is a kind of neurological conditions, is selected from delayed gastric emptying, notes damaged many moving obstacles (ADHD), phobia, somnopathy, apoplexy, insane, pain, anticholinergic agents is excessive, tobacco relies on, Parkinson's disease, memory injury, and cognitive function damage.The present invention includes compound of the present invention and be used to make the purposes of pharmaceutical preparation, wherein said pharmaceutical preparation is used for the treatment of the relevant illness of activity with individual acetylcholinesterase, and wherein said illness is a kind of neurological conditions, be selected from delayed gastric emptying, note damaged many moving obstacles (ADHD), phobia, somnopathy, apoplexy, insane, pain, anticholinergic agents is excessive, and tobacco relies on, Parkinson's disease, memory injury, and cognitive function damage.
In one embodiment, the present invention includes the method for a kind of treatment illness relevant with the activity of the acetylcholinesterase of individuality, described method is finished by using compound of the present invention, wherein said illness is selected from glaucoma, tumour illness, delayed gastric emptying, note damaged many moving obstacles (ADHD), phobia, apoplexy, multiple sclerosis, somnopathy, insane, pain, anticholinergic agents is excessive, tobacco relies on, cardiovascular disorder, for example, hypertension, infectation of bacteria, Meniere's disease, virus infection, allergy, and spasticity.The present invention includes compound of the present invention and be used to make the purposes of pharmaceutical preparation, wherein said pharmaceutical preparation is used for the treatment of the relevant illness of activity with individual acetylcholinesterase, and wherein said illness is selected from glaucoma, the tumour illness, delayed gastric emptying is noted damaged many moving obstacles (ADHD), phobia, apoplexy, multiple sclerosis, somnopathy, insane, pain, anticholinergic agents is excessive, and tobacco relies on, cardiovascular disorder, for example, hypertension, infectation of bacteria, Meniere's disease, virus infection, allergy, and spasticity.
In one embodiment, the present invention includes the method for a kind of treatment illness relevant with the activity of the acetylcholinesterase of individuality, described method is finished by using compound of the present invention, and wherein said illness is selected from delayed gastric emptying, note damaged many moving obstacles (ADHD), phobia, somnopathy, apoplexy, insane, pain, anticholinergic agents is excessive, and tobacco relies on.The present invention includes compound of the present invention and be used to make the purposes of pharmaceutical preparation, wherein said pharmaceutical preparation is used for the treatment of the relevant illness of activity with individual acetylcholinesterase, wherein said illness is selected from delayed gastric emptying, notes damaged many moving obstacles (ADHD), phobia, somnopathy, apoplexy, insane, pain, anticholinergic agents is excessive, and tobacco relies on.
In one embodiment, the present invention includes the method for a kind of treatment illness relevant with the activity of the acetylcholinesterase of individuality, described method is finished by using compound of the present invention, and wherein said illness is that anticholinergic agents is excessive.The present invention includes compound of the present invention and be used to make the purposes of pharmaceutical preparation, wherein said pharmaceutical preparation is used for the treatment of the relevant illness of activity with individual acetylcholinesterase, and wherein said illness is that anticholinergic agents is excessive.
In one embodiment, the method that the present invention includes above to be discussed, wherein said individuality is human.
Compound of the present invention can suppress the active of Pseudocholinesterase and discharge a kind of component in a kind of pharmacological activity reagent or the pharmacological activity reagent by hydrolytic action.Described in one embodiment pharmacological activity reagent is Q-H.In another embodiment, described pharmacological activity reagent is the salt of Q-H.In one embodiment, pharmacological activity reagent of the present invention is a kind of coagulase negative staphylococcus (CNS) active compound, it for example is a kind of monoamine oxidase B (MAO-B) inhibitor, for example those are proved and can be used for the treatment of Parkinsonian compound, for example, a kind of noradrenaline reuptake inhibitor, for example those are proved to be used for the treatment of and note damaged many moving obstacles (ADHD) or dejected compound, for example, tomoxetine (atomoxetine), desmethylimipramine (desipramine), nortriptyline (nortriptyline), protriptyline (protriptyline), and amoxapine (amoxapine); A kind of selectivity varies reuptake inhibithors (SSRI), for example those are proved the compound that can be used for the treatment of dejected, obsession or anxiety disorder, for example, fluvoxamine (fluvoxamine), and paroxetine (paroxetine); And the dual reuptake inhibithors of a kind of norepinephrine/varies, for example those are proved the compound that can be used for the treatment of dejected, stress incontinence or chronic pain, for example, and duloxetine (duloxetine).
In a kind of other embodiment, the present invention is a kind of method for the treatment of individual illness, and described method is finished by using compound of the present invention to described individuality.For example, described illness is a kind of neuroscience illness.
For example, described illness is individual memory injury, and is dejected, Parkinson's disease, and dementia is noted damaged many moving obstacles, obsession (OCD), anxiety disorder, stress incontinence, chronic pain, perhaps narcolepsy.
The compound that mixes the medicine of the bright or Physostigmine of favourable gas and particular category can provide additional or collaborative treatment effect for the patient.
Without wishing to be bound by theory, compound of the present invention is believed to suppress the active of described Pseudocholinesterase and therefore can effectively treats various illnesss, neuroscience illness for example, for example, mode by the transmission between treatment cholinergic disappearance and the increase neurone, the mode of the amount by increasing the amine in the synaptic cleft, the mode by sending amine to synaptic cleft or treat by increasing the mode of sending of in described central nervous system, carrying out pharmacological activity amine.Other illnesss that can use compound of the present invention to treat include, but are not limited to, cardiovascular illness or various infectation of bacteria.Advantage of the present invention comprises, for example, under the prerequisite of the change of pharmacological activity reagent not being carried out important structure, send described pharmacological activity reagent to cynapse, wherein said pharmacological activity reagent is the conditioning agent of neurotransmission for example, this transmission has produced the neurotransmission that may lack or reduce originally, thereby, treat disease or the illness relevant with the imbalance of neurotransmitters.Method of the present invention can increase the amount of described pharmacological activity reagent, and wherein said pharmacological activity reagent is neurotransmitters for example, thereby disease or the illness relevant with the disappearance of neurotransmitters compensated.
Therefore, compound of the present invention can be used among disease or other treatment of conditions, wherein said disease or other illnesss are relevant with pharmacological activity reagent, thereby interrupt, reverse or reduce the deterioration of described disease or other illnesss, perhaps promote the physiological processes that can be treated by pharmacological activity reagent, described pharmacological activity reagent is for example can be to transmitting the pharmacological activity reagent that relevant illness is treated with cynapse.
Description of drawings
What accompanying drawing 1 was described is the mechanism of the acetylcholinesterase inhibition of compound of the present invention.
Embodiment
Feature of the present invention and other details perhaps constitute the step among the present invention, perhaps as the combination of some part of the present invention, will be carried out more detailed description and are listed in the claims at this.Be understandable that embodiment of the present invention is to be expressed out and not to be construed as limiting the invention in the mode of setting forth.The feature of the principle described in the present invention can be used in the various technical scheme, and this does not deviate from scope of the present invention.
In one aspect, the present invention includes a kind of according to the compound shown in formula I or the formula II:
Or the acceptable salt of the medicine of this compound, wherein Q is selected from the structural formula shown in the table 1; R
1Be selected from hydrogen, unsubstituted alkyl, substituted alkyl, unsubstituted aralkyl, substituted aralkyl, unsubstituted iso-alkyl, and substituted iso-alkyl or R
1It is dead key; R
3, R
4And R
5Independently be selected from unsubstituted alkyl and hydrogen respectively separately.
In one embodiment, the present invention is a kind of according to the compound shown in the formula I.In another embodiment, the present invention is a kind of according to the compound shown in the formula II.
In one embodiment, the present invention is a kind of according to the compound shown in formula I or the formula II, wherein R
3, R
4And R
5In at least one be unsubstituted alkyl.In another embodiment, the present invention is a kind of compound, wherein R
3, R
4And R
5In at least two be unsubstituted alkyl.In another embodiment, the present invention is a kind of compound, wherein R
3, R
4And R
5All are unsubstituted alkyl.In one embodiment, the present invention is a kind of aforesaid compound, and wherein unsubstituted alkyl is a methyl.
In one embodiment, the present invention is a kind of compound, wherein R
1It is dead key.In one embodiment, R
1Be selected from hydrogen, substituted and unsubstituted alkyl.In another embodiment, R
1Be selected from hydrogen and unsubstituted alkyl.In one embodiment, R
1Be selected from methyl, hydrogen, ethyl, butyl, sec.-propyl, propyl group, and the tertiary butyl.In another embodiment, R
1Be hydrogen.In another embodiment, R
1It is unsubstituted alkyl.In one embodiment, R
1It is branched-chain alkyl.In one embodiment, R
1It is straight chained alkyl.In another embodiment, R
1Be selected from the sec.-propyl and the tertiary butyl.In one embodiment, R
1Be selected from methyl, ethyl, propyl group, and butyl.In one embodiment, R
1It is methyl.In one embodiment, R
1Be hydrogen or methyl.
In one embodiment, the present invention is a kind of compound, and wherein Q is selected from P, S, R, Z, Y, SS, JJJ, YY, EEE, UU, AA, FFF, CCC, U, T, X, V, P, Q ', U, BB, CC, DD, SSS, TTT, MM, UU, and XX.In another embodiment, Q is selected from X, V, P, Q ', U, R, S, Y, T, Z, AA, BB, CC, DD, SSS, TTT, MM, UU, and XX.
In another embodiment, the present invention is a kind of compound, and wherein Q is represented by following structural formula: V, Y, AA, DD, FF, HH, II, JJ, OO, PP, VV, WW, XX, ZZ, AAA, BBB, FFF, HHH, III, JJJ, KKK, LLL, MMM, AAAA, CCCC, EEEE, FFFF, HHHH, MMMM, QQQQ, UUUU, WWWW, XXXX, ZZZZ, AAAAA, CCCCC, DDDDD, MMMMM, PPPPP, QQQQQ, RRRRR, VVVVV, WWWWW, XXXXX, YYYYY, 2D, 2E, 2G, 2H, 2I, 2J, 2K, 2M, 2n, 2O, 2P, 2Q, 2R, 2T, 2V, 2W, 2X, 2Y, 2CC, 2DD, 2OO, 2PP, 2RR, 2TT, 2UU, 2VV, 2XX, 2YY, 2AAA, 2CCC, 2HHH, 2SSS, 2TTT, 2ZZZ, 2UUU, 2AAAA, 2GGGG, 2HHHH, 2IIII, 2MMMM, 2NNNN, 2OOOO, 2PPPP, 2QQQQ, 2RRRR, 2TTTT, 2UUUU, 2VVVV, 2AAAAA, 2BBBBB, 2DDDDD, 2EEEEE, 2FFFFF, 2GGGGG, 2HHHHH, 2IIIII, 2JJJJJ, 2NNNNN, 2OOOOO, 2QQQQQ, 2RRRRR, 2TTTTT, 2WWWWW, 2XXXXX, 2ZZZZZ, 3A, 3B, 3E, 3F, 3H, 3I, 3M, 3N, 3O, 3P, 3S, 3T, 3U, 3V, 3X, 3AA, 3BB, 3DD, 3EE, 3FF, 3GG, 3HH, 3II, 3JJ, 3LL, 3MM, 3OO, 3PP, 3SS, 3TT, 3UU, 3VV, 3WW, 3XX, 3YY, 3ZZ, 3AAA, and 3CCC.
In another embodiment, the present invention is a kind of compound, and wherein Q is represented by following structural formula: S, X, AA, CC, EE, II, KK, LL, MM, NN, OO, PP, QQ, RR, SS, TT, UU, YY, CCC, DDD, EEE, GGG, SSS, TTT, UUU, VVV, WWW, XXX, YYY, ZZZ, BBBB, DDDD, GGGG, JJJJ, IIII, KKKK, LLLL, NNNN, OOOO, PPPP, RRRR, SSSS, TTTT, VVVV, YYYY, BBBBB, EEEEE, FFFFF, GGGGG, HHHHH, IIIII, JJJJJ, KKKKK, LLLLL, NNNNN, OOOOO, SSSSS, TTTTT, UUUUU, ZZZZZ, 2A, 2B, 2C, 2F, 2L, 2R, 2S, 2U, 2W, 2X, 2Z, 2AA, 2BB, 2CC, 2DD, 2EE, 2FF, 2GG, 2HH, 2II, 2JJ, 2KK, 2LL, 2MM, 2NN, 2QQ, 2SS, 2WW, 2YY, 2ZZ, 2AAA, 2BBB, 2DDD, 2EEE, 2FFF, 2GGG, 2HHH, 2III, 2JJJ, 2KKK, 2LLL, 2MMM, 2NNN, 2OOO, 2PPP, 2QQQ, 2RRR, 2VVV, 2WWW, 2XXX, 2YYY, 2AAAA, 2BBBB, 2CCCC, 2DDDD, 2EEEE, 2FFFF, 2IIII, 2JJJJ, 2KKKK, 2LLLL, 2NNNN, 2PPPP, 2SSSS, 2VVVV, 2WWWW, 2XXXX, 2YYYY, 2ZZZZ, 2AAAAA, 2CCCCC, 2KKKKK, 2LLLLL, 2MMMMM, 2PPPPP, 2UUUUU, 2VVVVV, 2YYYYY, 3A, 3C, 3D, 3G, 3J, 3K, 3L, 3M, 3Q, 3W, 3Y, 3Z, 3BB, 3CC, 3KK, 3NN, 3PP, 3QQ, 3RR, 3SS, 3YY, 3BBB, and 3XXX.
In another embodiment, the present invention is a kind of compound, and wherein Q is represented by following structural: P, Q ', R, T, Z, U, BB, and OOO.
In another embodiment, the present invention is a kind of compound, and wherein Q is represented by structural formula GG.
In one embodiment, the present invention is a kind of compound, and described compound is selected from compound 2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30, and 31.In another embodiment, described compound is selected from compounds X, V, P, Q ', U, R, S, Y, T, Z, AA, BB, CC, DD, SSS, TTT, MM, UU, and XX.
In one embodiment, the present invention is a kind of pharmaceutical composition, and described pharmaceutical composition comprises the acceptable salt of the medicine of compound of the present invention or this compound.In another embodiment, the present invention is a kind of pharmaceutical composition, and described pharmaceutical composition comprises the acceptable salt of medicine and a kind of vehicle of compound of the present invention or this compound.Vehicle is a kind of inactive substance, is used as the carrier of the activeconstituents of compound of the present invention.In one embodiment, compound of the present invention is not easy to be applied and is not easy and absorbed by human body, therefore, itself and excipient composition is together used.
Compound of the present invention can suppress the active of Pseudocholinesterase and discharge a kind of component in a kind of pharmacological activity reagent or the pharmacological activity reagent by hydrolytic action.A kind of component in described in one embodiment pharmacological activity reagent or the described pharmacological activity reagent is Q-H.Listed the structural formula of Q in the table 1 below.In the structural formula of Q in following table 1, described structure
What represent is the point that described structure Q is connected with formula I and formula II.When described structure
When being replaced by hydrogen, a kind of component in described pharmacological activity reagent or the described pharmacological activity reagent is Q-H.
Table 1
Especially, compound of the present invention is by being at war with and suppressing Pseudocholinesterase with a kind of natural compounds (for example, vagusstoff (ACh) or BuCh (BuCh)), and wherein said natural compounds is incorporated on the described Pseudocholinesterase.
When described Pseudocholinesterase is prevented from carrying out deactivation such as the such natural compounds of neurotransmitters vagusstoff, described Pseudocholinesterase is suppressed to a certain extent, under the situation that does not have described compound, Pseudocholinesterase should act on described neurotransmitters.As shown in accompanying drawing 1, thereby described compound combines with described Pseudocholinesterase and generates a kind of carboxylamine esterase.The hydrolysis of described carboxylamine esterase is considerably slower than for example a kind of hydrolysis of ethanoyl enzyme, and wherein said ethanoyl enzyme is that the hydrolytic action by its endogenous substrate vagusstoff forms.When described carboxylamine esterase generation hydrolysis, compound of the present invention has stopped for the inhibition of described Pseudocholinesterase.By the hydrolysis reaction of described carboxylamine esterase, a kind of d/d compound, for example a kind of amine, for example Q-H becomes at least a component in a kind of pharmacological activity reagent.In one embodiment, Q-H is a kind of salt.
The hydrolysis of compound of the present invention can be the hydrolysis of being undertaken by enzyme (for example, Pseudocholinesterase), or the hydrolysis of not undertaken by enzyme, for example be the hydrolysis of being undertaken by acid (for example, hydrochloric acid in gastric juice), thereby discharge at least a component in the pharmacological activity reagent.
Here employed described term " by the hydrolysis that takes place with enzyme reaction " refers to a two-step reaction: compound of the present invention and a kind of enzyme generate a kind of carboxylamine esterase, and the decomposition reaction of described carboxylamine esterase by taking place with the water reaction.
Same, here employed described term " by reacting the hydrolysis that takes place with Pseudocholinesterase " refers to a two-step reaction: compound of the present invention and described Pseudocholinesterase generate a kind of carboxylamine esterase, and described carboxylamine esterase is by reacting the decomposition reaction that takes place with water.
The Pseudocholinesterase that compound suppressed described by the present invention can be, for example, is selected from least a in the group of being made up of acetylcholinesterase (AChE) or butyrylcholine esterase (BuChE).Compound of the present invention can be independent acetylcholine esterase inhibition, independent inhibition butyrylcholine esterase perhaps can suppress acetylcholinesterase and butyrylcholine esterase simultaneously with similar degree or different degree.
Acetylcholinesterase be positioned at can be excited film on and vagusstoff carried out deactivation.Described can excited film can be a kind of presynaptic neuron or postsynaptic neuron.Acetylcholinesterase is also referred to as the specificity Pseudocholinesterase.Butyrylcholine esterase is arranged in and can organizes for example hemocyte by excited film and non-neuron.Butyrylcholine esterase is also referred to as pseudocholine esterase or unspecific cholinesterase.Acetylcholinesterase and butyrylcholine esterase are the conditioning agents that the cholinergic nerve in central nervous system (brain and spinal cord), peripheral nervous system and the autonomic nervous system (parasympathetic nervous system and sympathetic nervous system) transmits.
The hydrolysis of the carboxylamine key by compound of the present invention, a kind of compound that is released out for example comprises the compound of amine Q-H becoming at least a component in a kind of pharmacological activity reagent.Here employed described term " becomes at least a component in a kind of pharmacological activity reagent " and refers to a kind of release of compound, wherein said compound for example is a kind of compound Q-H that contains amine, and this release is the result of the hydrolysis of described carboxylamine esterase.Described compound Q-the H that is discharged by the hydrolytic action of described carboxylamine esterase is at least a portion of a kind of pharmacological activity reagent.In one embodiment, the described compound that is discharged by the hydrolytic action of described carboxylamine esterase is a kind of prodrug.Here employed described term " prodrug " refers to a kind of compound that is applied, and described compound is not an actual drug desired in the treatment plan, and it can be converted to the actual drug of expecting by metabolic process in described treatment.Afterwards, can modify, thereby discharge a kind of pharmacological activity reagent described prodrug.In another embodiment, the described compound Q-H itself that is discharged by the hydrolytic action of described carboxylamine esterase is exactly described pharmacological activity reagent.Therefore, compound of the present invention has dual role: as the inhibitor of Pseudocholinesterase, and as the delivery medium of pharmacological activity reagent Q-H.
The hydrolysis reaction of compound of the present invention that can discharge pharmacological activity reagent Q-H is represented by the scheme of following detailed description:
Here employed described term " pharmacological activity reagent " refers to a kind of compound, QH, described compound can by change in biological procedures directly or the molecule that relates to indirectly (for example, neurotransmitters, peptide, albumen) activity, location and/or express and influence described biological procedures.For example, described pharmacological activity reagent, QH is a kind of coagulase negative staphylococcus (CNS) active compound, or a kind of compound that is used to carry out the cardiovascular treatment, or a kind of antimicrobial compounds.
For example, described coagulase negative staphylococcus (CNS) active compound is a kind of known or be believed to effectively be used for the treatment of the compound of following disease: Alzheimer's disease, Parkinson's disease, note damaged many moving obstacles (ADHD), dejected, obsession (OCD), anxiety disorder, stress incontinence, chronic pain, perhaps narcolepsy.
For example, coagulase negative staphylococcus of the present invention (CNS) active compound is a kind of monoamine oxidase B (MAO-B) inhibitor, for example, and Tranylcypromine; A kind of noradrenaline reuptake inhibitor, tomoxetine for example, desmethylimipramine, nortriptyline, protriptyline, and amoxapine; A kind of selectivity varies reuptake inhibithors (SSRI), for example those are proved the compound that can be used for the treatment of dejected, obsession or anxiety disorder, for example, fluvoxamine, and paroxetine; And the dual reuptake inhibithors of a kind of norepinephrine/varies, for example, duloxetine.
In addition, the pharmacological activity reagent that can be used according to the present invention for example is, but is not limited to betahistine (betahistine), amlodipine (amlodipine), Rimantadine (rimantadine), decarboxylation loratadine (desloratadine), U.S. dollar amine (memantine), lyrica (pregabalin), baclofen (baclofen), Symmetrel (amantadine), perhaps Ciprofloxacin (ciprofloxacin).These reagent can be used to treatment or prevention Meniere's disease, hypertension, virus infection, allergy, Alzheimer's disease, neuropathic pain, spasticity, Parkinson's disease, perhaps infectation of bacteria.
Described pharmacological activity reagent, Q-H can be a kind of prodrug or precursor substance, and its metabolism is a kind of compound, and described compound contains primary amine or the secondary amine in the pharmacological activity reagent.
Described pharmacological activity reagent preferably changes biological procedures in a kind of mode that can produce target effect, the described mode that can produce target effect for example is, improve biological procedures, alleviate the symptom of damage or disease, perhaps slow down and/or reverse the deterioration of disease.For example, hydrolytic action by compound of the present invention, the described amine that is released out can become at least a component of pharmacological activity reagent, the cell incident of the decomposition that it can be by reducing or stop described neurotransmitters, the release by participating in causing extra neurotransmitters, by suppressing absorbing and/or increasing the amount of the neurotransmitters in the cynapse by increasing synthesizing of described neurotransmitters of described neurotransmitters.
Described pharmacological activity reagent can, for example, cause the increase of vagusstoff of the cynapse of described central nervous system neurons, this increase can compensate for example cholinergic disappearance in the Alzheimer's disease patient, thereby promotes neuronic transmission and finally alleviate or improve the symptom of described Alzheimer's disease.The symptom that is accompanied by Alzheimer's disease comprises: the damage of cognitive function, disoriented behavior, the change of personality, language and understand difficulty and the damage of gait and action aspect.The someone proposes, and the reduction of cholinergic function is the reason that occurs of the symptom of the Alzheimer's disease (article of delivering in European J.Pharmacol. " European pharmacology magazine " 346:1-13 in 1998 referring to people such as Benzi G..; The article that Korczyn A.D. delivered in Exp.Opin.Invest.Drugs " expert opinion of research property medicine " 9:2259-2267 in 2000).
The reduction of described cholinergic function may be to be synthesized or the minimizing of the amount of d/d vagusstoff, and neurone responds to the forfeiture of ability of vagusstoff or the deactivation of acetylcholinesterase.Comprise for the current methods of treatment of Alzheimer's disease and to use the compound that can the increase the cholinergic signal (article of delivering in Pharmacotherapy " pharmacotherapy " 20:1-12 in 2000 referring to Jann M.W.; The article that Bachurin S.O. delivered in Med.Res.Rev " medical research review " 23:48-88 in 2003).Yet these compounds have the effect of appropriateness, and gastrointestinal problems and fatigue are for example felt sick in low response rate (being typically about 30%-50%) and numerous side effects.In one embodiment, compound of the present invention can acetylcholine esterase inhibition and is become a kind of at least a component of pharmacological activity reagent by hydrolytic action, wherein said pharmacological activity reagent can increase the neurotransmitters of the cynapse of central nervous system neurons, for example vagusstoff.Therefore, for example, compound of the present invention can acetylcholine esterase inhibition, this has reduced the vagusstoff of Alzheimer's disease patient's synapse, and discharge pharmacological activity reagent, described pharmacological activity reagent can common or is divided other to increase neurotransmitters in the described cynapse.
The obstacle that cholinergic disappearance shows as other equally is Parkinson's disease for example, stein-leventhal syndrome, vascular dementia and Down's syndrome (article of delivering in the Exp.Opin.Invest.Drugs expert opinion of medicine " research property " 9:2259-2267 in 2000 referring to Korczyn A.D.).Therefore, compound of the present invention can be used to increase described vagusstoff equally in these obstacles.
Same, described pharmacological activity reagent can cause suffering from the increase of the neurotransmitters Dopamine HCL in Parkinsonian patient's the central nervous system, thereby promotes neuronic transmission and then reduce described symptoms of Parkinson's disease.The increase of described Dopamine HCL can be the indirect consequence of the hydrolytic action of described carboxylamine esterase, described carboxylamine esterase is by hydrolytic action delivery of pharmacologically active agent, described pharmacological activity reagent passes through, for example, suppress described Dopamine HCL the decomposition that absorbs, prevents described Dopamine HCL again, increase the release of described Dopamine HCL or increase the Dopamine HCL in the cynapse as a kind of synthetic dopamine precursor (for example, levodopa amine).
Therefore, described pharmacological activity reagent can be the pharmacological activity reagent of a kind of central nervous system class (brain, spinal cord).Here employed described term " central nervous system class " refers to the generation effect in described central nervous system of described pharmacological activity reagent.
The pharmacological activity reagent of the pharmacological activity reagent that described pharmacological activity reagent can also be a kind of peripheral nervous system class or a kind of autonomic nervous system class (parasympathetic nervous system and sympathetic nervous system).Here employed described term " peripheral nervous system class " and " autonomic nervous system class " refer to a kind of pharmacological activity reagent, Q-H, generation effect in described peripheral nervous system and autonomic nervous system respectively.
Described pharmacological activity reagent can comprise it prodrug and other structural derivative (for example, isomer or steric isomer, d for example, l, dl, R, S, and RS steric isomer) and functional deriv, in these materials, preferably having can substituted primary amine and secondary amine.More specifically, described pharmacological activity reagent can also comprise, for example, and the salt of described reagent, hydrate, solvate, zwitter-ion, and other forms.
In one embodiment, compound of the present invention is
Wherein R is a hydrogen, unsubstituted alkyl, substituted alkyl, unsubstituted aralkyl, substituted aralkyl, unsubstituted iso-alkyl, perhaps substituted iso-alkyl.In one embodiment, R is a hydrogen.
In another embodiment, compound of the present invention is
Wherein R is a hydrogen, unsubstituted alkyl, substituted alkyl, unsubstituted aralkyl, substituted aralkyl, unsubstituted iso-alkyl, perhaps substituted iso-alkyl.In one embodiment, R is a hydrogen.
In another embodiment, compound of the present invention is
Wherein R is a hydrogen, unsubstituted alkyl, substituted alkyl, unsubstituted aralkyl, substituted aralkyl, unsubstituted iso-alkyl, perhaps substituted iso-alkyl.In one embodiment, R is a hydrogen.
In another embodiment, compound of the present invention is
Wherein R is a hydrogen, unsubstituted alkyl, substituted alkyl, unsubstituted aralkyl, substituted aralkyl, unsubstituted iso-alkyl, perhaps substituted iso-alkyl.In one embodiment, R is an alkyl.
In another embodiment, compound of the present invention is
Wherein R is a hydrogen, unsubstituted alkyl, substituted alkyl, unsubstituted aralkyl, substituted aralkyl, unsubstituted iso-alkyl, perhaps substituted iso-alkyl.In another embodiment, R is a methyl.
In another embodiment, compound of the present invention is
In another embodiment, compound of the present invention is a kind of bright derivative of sharp gas, for example,
In another embodiment, compound of the present invention is a kind of Physostigmine derivative, for example,
Described term " alkyl " that use separately or that be used as the part in the half bigger family comprises straight chain, side chain or the cyclic saturated hydrocarbon chain, wherein contains one to 12 carbon atom.
Here employed described term " iso-alkyl " is a kind of alkyl group, and one or more carbon atom is replaced by heteroatoms.
Described term " aryl " that use separately or that for example in " aralkyl " or " aralkoxy ", use as the part in the half bigger family, be carbocyclic ring aromatic nucleus system (for example, phenyl), thick and the fragrant member ring systems (for example, naphthyl and anthryl) of many cyclophanes and with carbocyclic ring non-aromatic ring system thick and aromatic nucleus system (for example, 1,2,3,4-tetralyl and indanyl), it has five to about ten four carbon atoms.
That use separately or as the described term " iso-aryl " that the part in the half bigger family for example uses in " different aralkyl " or " different aralkoxy ", refer to and have five to 14 atoms and have at least one heteroatomic aromatic nucleus system.Preferably, an iso-aryl has from one to about four heteroatomss.Heteroatoms in those preferred iso-aryls is selected from the group of being made up of following radicals: oxygen, sulphur, nitrogen, phosphorus and halogenide.The example of iso-aryl ring comprises pyrazolyl, furyl, imidazolyl, isoxazolyl, the oxadiazoles base, oxazolyl, pyrryl, pyridyl, pyrimidyl, purine radicals, pyridazinyl, pyrazinyl, thiazolyl, thiadiazolyl group, isothiazolyl, triazolyl, thienyl, 4,6-dihydro-thiophene [3,4-c] pyrazolyl, 5,5-dioxy-4,6-dihydro-thiophene [3,4-c] pyrazolyl, thianaphthenyl (thianaphthenyl), 1,4,5,6-tetrahydro cyclopentyl pyrazolyl, carbazyl, benzimidazolyl-, benzothienyl, benzofuryl, indyl, azaindolyl, indazolyl, quinolyl, benzotriazole base, benzothiazolyl, diazosulfide base, benzoxazolyl, benzimidazolyl-, isoquinolyl, pseudoindoyl, acridyl, and benzisoxa oxazolyl.Preferred iso-aryl group is a pyrazolyl, furyl, pyridyl, quinolyl, indyl and imidazolyl.
Here employed aromatic alkyl group is a kind of aryl substituent, and described aryl substituent is connected with a kind of compound by a straight chained alkyl group or a branched alkyl group with from one to 12 carbon atom.
Here employed different group of naphthene base is a kind of heterocyclic substituent, and described heterocyclic substituent is connected with a kind of compound by a straight chained alkyl group or a branched alkyl group with from one to 12 carbon atom.
Here employed different aromatic alkyl group is a kind of iso-aryl substituting group, and described iso-aryl substituting group is connected with a kind of compound by a straight chained alkyl group or a branched alkyl group with from one to 12 carbon atom.
An aryl (comprising aralkyl, aralkoxy and similar group) or iso-aryl (comprising different aralkyl and different aralkoxy and similar group) can contain one or more substituting group.Suitable substituent example comprises aliphatic group, aromatic yl group, halogen alkoxy base, iso-aryl group, halogen and hydroxyl.
In one embodiment, compound of the present invention comprises a kind of isomer or steric isomer (for example, d, l, dl, R, S, perhaps RS).In all represented structures of the present invention, can be understood that, except as otherwise noted, no matter whether a kind of compound is represented as (+,-), dl (DL) or (R) (S), the present invention is intended to comprise the racemic mixture of described compound, the perhaps pure component of a kind of form of described compound, for example, " d " or " l ", " R " or " S ".
The method that is used to prepare compound of the present invention belong to those skilled in the art's knowledge category (referring to, for example U.S. Patent No. 5,665,880; No.5,677,457; And WO 97/14694, be taught in this complete being introduced into as a reference in the above-mentioned document).
In one embodiment, thus can activate the method that generates a kind of amine that is activated by the amine groups to a kind of compound finishes the synthetic of compound of the present invention.The described amine that is activated can be separated and react with the phenolic groups of another compound, thereby generates compound of the present invention.For example, a primary amine can be converted to and be a kind of isocyanate.Perhaps, amine can be converted to and be urea chloride.Amine can also be activated and be used in position to carry out the synthetic of compound of the present invention, for example by (for example with amine and the active agent that contains carbonyl chlorine, phosgene, solid phosgene) reacts, with described amine and the active agent that contains the nitro-phenoxy carbonyl group (for example, two-4-nitrophenyl carbonate, 4-nitrophenyl chlorocarbonate) react, perhaps described amine and carbonyl dimidazoles are reacted.Can use all ingredients that catalysis is carried out in the activation of amine and each step of synthetic of compound of the present invention, wherein said all ingredients is for example acid, and alkali, and nucleophilic reagent are used singly or in combination.
In another embodiment, finish the synthetic of compound of the present invention thereby can activate the method that generates a kind of phenol that is activated by phenolic groups to a kind of compound.The amine groups of the described phenol that is activated and another compound is reacted.The activation of described phenol can be finished by variety of way, for example by (for example with described phenol and the active agent that contains carbonyl chlorine, phosgene, solid phosgene) reacts, with described phenol and the active agent that contains the nitro-phenoxy carbonyl group (for example, two-4-nitrophenyl carbonate, 4-nitrophenyl chlorocarbonate) react, perhaps described phenol and carbonyl dimidazoles base are reacted.Can use all ingredients Pyrogentisinic Acid's activation and each step of synthetic of compound of the present invention to carry out catalysis, wherein said all ingredients is for example acid, and alkali, and nucleophilic reagent are used singly or in combination.
Can analyze compound of the present invention by the analytical procedure of knowing, comprise nuclear magnetic resonance.
Can use known method to carry out the synthetic of compound of the present invention; for example: compound of the present invention can synthesize by for example following method: phenolic hydroxyl group and carbonyl dimidazoles (CDI) are reacted; add acetic acid and described amine afterwards; thereby generate described fragrant formamyl ester (article of delivering in J.Heterocyclic Chem " heterocyclic chemistry magazine " 37:331-333 in 2000 referring to people such as Gao, being taught in this complete be introduced into as a reference in the above-mentioned article).
The someone has described the use urea chloride and generated the fragrant formamyl ester (article of delivering in Biophysica Acta " biological chemistry and biophysics journal " 1120:262-266 in 1992 referring to people such as Marta from geneserine; The article that people such as Marta delivered in Biomed Biochem Acta " biomedicine and Biochemical Journal " 47:285-288 in 1998; The article that people such as Marta delivered in Life Sci. " life science " 43:1921-1928 in 1988 is taught in this complete being introduced into as a reference in the above-mentioned article).
Also the someone described phenolic hydroxyl group in the building-up reactions of fragrant formamyl ester and the reaction between the urea chloride (article of delivering in Bioorg Med Chem " bioorganic chemistry and pharmaceutical chemistry " 11:1935-1955 in 2003 referring to people such as Toda; The article that people such as Kogen delivered in Org Lett " organic knowledge " 4:3359-3362 in 2002; The article that people such as article that people such as Mustazza delivered in Eur J.MedChem " European pharmaceutical chemistry magazine " 37:91-109 in 2002 and Sterling delivered in J Med Chem " pharmaceutical chemistry magazine " 45:5260-5279 in 2002 is taught in this complete being introduced into as a reference in the above-mentioned article).
Gone out the benzene serine (Ser.) (referring to U.S. Patent No. 6 by the prepared in reaction between geneserine and isocyanate, 495,700, be taught in this complete being introduced into as a reference in the above-mentioned document), described reaction is carried out in glycol dimethyl ether under ar gas environment, and has the hexane solution of the n-Butyl Lithium of catalytic amount.
People such as Mustazza in 2002 in Eur J.Med Chem " European pharmaceutical chemistry magazine " 37:91-109 and people such as Yuv in J Med Chem " pharmaceutical chemistry magazine " 44:4062-4071, also used isocyanate in calendar year 2001, be taught in this complete being introduced into as a reference in the above-mentioned article.
In a kind of further embodiment, compound of the present invention is the compound shown in the formula III:
Or the acceptable salt of the medicine of this compound, wherein Q is suc as formula described in the I.
In another embodiment, compound of the present invention is the compound shown in the formula IV:
Or the acceptable salt of the medicine of this compound, wherein Q is suc as formula described in the I.
In another embodiment, compound of the present invention is the compound shown in the formula V:
Or the acceptable salt of the medicine of this compound, Q wherein, R
3, R
4, and R
5Described in II.
In another embodiment, compound of the present invention is the compound shown in the formula (VI):
Or the acceptable salt of the medicine of this compound, wherein Q is suc as formula described in the II.
In one embodiment, described pharmacological activity reagent, QH is that a kind of memory promotes reagent.In another embodiment, described pharmacological activity reagent, QH is that a kind of cognitive function promotes reagent.
Here employed described term " memory promotion reagent " refers to a kind of like this compound, it can improve individual memory, prevention or reduce the decline of individual memory or participate in biological procedures, wherein said biological procedures relate to memory function.
Can be promoted reagent to carry out promoted described memory process by described memory can be that memory is consolidated, the process of storage fresh information is (referring to " Neuroscience:Exploring The Brain " neuroscience: for the exploitation of brain " " in long-term memory, people such as Bear M.F., Williams ﹠amp; Wilkins, Baltimore, Maryland, the 19th chapter, 517-545 page or leaf, 1996 years; The article that McGaugh J.L delivered in Science " science " 287:248-251 in 2000 is taught in this complete being introduced into as a reference in the above-mentioned article); Short-term memory (being also referred to as " working memory "), the new in this course information that obtains is retained at short notice and the information of described new acquisition can be used to carry out further information processing (referring to " Neuroscience:Exploring The Brain " neuroscience: for the exploitation of brain " ", people such as Bear M.F., Williams ﹠amp; Wilkins, Baltimore, Maryland, the 19th chapter, 517-545 page or leaf, 1996 years; The article that McGaugh J.L delivered in Science " science " 287:248-251 in 2000; The article that people such as Becker J.T delivered in Brain andCognition " brain with cognitive " 41:1-8 in 1999 is taught in this complete being introduced into as a reference in the above-mentioned article); Declarative memory, this memory are (referring to " Neuroscience:Exploring The Brain " neuroscience: for the exploitation of brain " ", people such as Bear M.F., Williams ﹠amp for the memory of the fact and incident; Wilkins, Baltimore, Maryland, the 19th chapter, 517-545 page or leaf, 1996 years; The article that McGaugh J.L delivered in Science " science " 287:248-251 in 2000; The article that people such as Tulving E. delivered in Science " science " 247:301-306 in nineteen ninety; The article that people such as Squire L.R delivered in Proc.Natl.Acad.Sci. " PNAS " 93:13515-13522 in 1996 is taught in this complete being introduced into as a reference in the above-mentioned article); Nondeclarative memory (being also referred to as " silent meeting knowledge " or " Tacit Knowledge "), this memory is (referring to " Neuroscience:Exploring The Brain " neuroscience: for the exploitation of brain " " for the memory of technical ability or behavior, people such as Bear M.F., Williams ﹠amp; Wilkins, Baltimore, Maryland, the 19th chapter, 517-545 page or leaf, 1996 years; The article that McGaugh J.L delivered in Science " science " 287:248-251 in 2000 is taught in this complete being introduced into as a reference in the above-mentioned article); Perhaps attention is known power, recaptures power or confining force.
In another embodiment, described pharmacological activity reagent, QH is that a kind of cognitive function promotes reagent.Here employed described term " cognitive function promotion reagent " refers to a kind of like this compound, it can promote and the individual relevant activity of thinking, study and acquire knowledge, prevention or reduce individual thinking, study and acquire knowledge ability decline or participate in biological procedures, wherein said biological procedures relates to thinking, study and acquire knowledge aspect.The decline of the ability of described thinking, study and acquire knowledge (a kind of cognition dysfunction) may be another central nervous system or peripheral nervous system or autonomic nervous system diseases (for example, Alzheimer's disease) or the result of illness, perhaps relevant with above-mentioned disease or illness.Can be promoted reagent to carry out promoted described cognitive process by described cognitive function can estimate with behavioral standard and behavior detection, and aforesaid method can further define successively at the cognitive function described in the process of described study, thinking and acquire knowledge and promote the position that reagent plays a role.Those skilled in the art should have the ability that those are suitable as cognitive function and promote the reagent of reagent to differentiate and estimate.
At formula I, formula II, formula III, formula IV, formula V, and in the compound shown in the formula VI, described substructure Q can represent the pharmacological activity reagent that contains amine arbitrarily, for example, tomoxetine, desmethylimipramine, nortriptyline, fluvoxamine, duloxetine, protriptyline, amoxapine, Tranylcypromine, paroxetine, betahistine, amlodipine, hexahydrodesoxyephedrine, Rimantadine, decarboxylation loratadine, leoponex, dorzolamide, hydrogen chlorobenzene thiophene pyridazine, lisinopril, lomefloxacin, melphalan, Nepafenac, lyrica, Riluzole, valacyclovir, Transbroncho, aminoglutethimide, amoxycilline Trihydrate bp, the Ampicillin Trihydrate, baclofen, amrinone, benazepril, Bupropion, Ciprofloxacin, dapsone, diclofenac, enoxacin, Tibutol, gabapentin, Vasoxyl, midodrine, Ritalin, norepinephrine, pseudoephedrine, Ramipril, Sertraline, SB 209509, cinacalcet, benzoctamine, isometheptene, Euspirol, Symmetrel, U.S. dollar amine, metoclopramide, hexosamine, afloqualone, aminohippuric acid, aminosallcylic acid, amodiaquine, amsacrine, Ah's prednylidene 21-diethylaminoacetatte, Quinacrime, benzocaine, bumetanide, Thiabutazide, carbutamide, carvedilol, cefaclor, cephalo azanol benzyl, cefroxadine, Cephradine, chlordiazepoxide, chloroprocaine, clortermine, ciclacillin, cyclopenthiazide, seromycin, mercaptamine, Wy-16225, dobutamine, eflornithine, racephedrine, suprarenin, epirubicin, she is for forint, Phenfluoramine, flucytosine, Tecramine, Furosemide, L-glutamic acid, glutamine, gsh, glycine, histamine, hydralazine, hydrochlorothiazide, idarubicin, imipenum, iopanoic acid, Isocaine, Racemic isoproterenol, Xuprin restrains his life, Lamivudine, lamotrigine, levodopa, lofexidine, mecamylamine, vialidon, mephentermine, metaraminol, methyldopa, metirosine, neamine, fluorinacid, nimodipine, nomefensine, Nylidrine, oxamniquine, oxyfedrine, perhexiline, phenmetrazine, Phenylpropanolamine, pipemidic acid, piperazine, pipradrol, pramipexole, primaquine, procainamide, Procarbazine, Pyrimethamine hcl, quinethazone, sisomicin, Sparfloxacin, spectinomycin, sulfacitine, suladimethoxydiazine, Sulphadoxine, Sulphaguanidine, sulfaguanole, sulfamethoxypyridazine, Sulfametoxydiazine, sulfamerazine, sulfamethazine, methylene sulfonamide thiadiazoles, Sulfamethomidine, sulfisomezole, sulfanilamide (SN) Sulfafurazole, N1-monoacetyl sulfisoxazole, sulfanilamide (SN) CS61, Tamsulosin, thiamphenicol glycinate, timonacic, tinoridine, tizanidine, tolazoline, tretoquinol, Urocaudol, trichlormethiazide, trientine, trimethoprim, trimetrexate, tromethane, troxipide, tryptophane, zalcitabine, clinic effect of alendronate, L-Ala, arginine, asparagine, aspartic acid, halfcystine, L-glutamic acid, Histidine, Isoleucine, leucine, Methionin, methionine(Met), phenylalanine, proline(Pro), Serine, Threonine, tyrosine, Xie Ansuan, Deferoxamine, the wheat salad is bright, phentolamine, VitB1, adefovir ester, adenosine, Alatrofloxacin, alendronate sodium, perhexiline maleate, almotriptan, Lotronex, amifostine, aminolevulinic acid, amlexanox, amprenavir, anagrelide, A Keer is fixed, and A Rui is smooth, argatroban, atovaquone, brimonidine, Bromfenac, Cabergoline, Candesartan, carbidopa, Cefditoren pivoxil Cephalosporins, cidofovir, cisapride, clofarabine, colestipol, conivaptan, cytosine arabinoside, ground La Luosi, Delavirdine, dexmedetomidine, right Methylphenidylacetate, remove the hydroxyl glycosides, Dihydroergotamine Mesilate, dolasetron, Doxazosin, Dx, emtricitabine, enalapril, felodipine, epinastine, erlotinib, ertapenem, omeprazole, R-ETODOLAC, Famciclovir, famotidine, Fenoldopam, fomepizole, fosamprenavir, Gatifloxacin, ganciclovir, Gefitinib, gemcitabine, gemifloxacin, Ge Lapasha star, imatinib, Imiquimod, Irb, Isrodipine, Levothyroxine, gonadotropin, the amino-laevulic acid methyl esters, metformin, mitoxantrone, moexipril, naratriptan, Nelzarabine, Moxifloxacin, nicardipine, nisoldipine, nizatidine, olanzapine, Oseltamivir, olmesartan medoxomill, oxaliplatin, Pamidronic Acid, pantoprazole, pemetrexed disodium, Penciclovir, pergolide, perindopril, Propafenone, quinapril, rabeprazole, Ranitidine HCL, risatriptan, sevelamer, Virga, sumatriptan, tacrine, Tadalafil (Cialis), Tegaserod, tenofovir, terazosin, Tigecycline, Tirofiban, torasemide, Trolapril, trovafloxacin, valacyclovir, valganciclovir, valsartan, Vardenafil, zalcitabine and zolmitriptan.
According to the present invention, a primary amine or secondary amine can be covalently bond on this bright, for example bright the or Physostigmine of Li Wasi.
Described term " desmethylimipramine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula P
1Be methyl, and described structure
Replaced by hydrogen.
Described term " nortriptyline " refers to a kind of pharmacological activity reagent, and wherein Q is represented by described structural formula Q ', R
1Be methyl, and described structure
Replaced by hydrogen.
Described term " fluoxetine " refers to a kind of pharmacological activity reagent, and wherein Q is represented by described formula R, R
1Be methyl, and described structure
Replaced by hydrogen.
Described term " fluvoxamine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula S
1Be methyl, and described structure
Replaced by hydrogen.
Described term " duloxetine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula T
1Be methyl, and described structure
Replaced by hydrogen.
Described term " protriptyline " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula U
1Be methyl, and described structure
Replaced by hydrogen.
Described term " amoxapine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula V
1Be dead key, and described structure
Replaced by hydrogen.
Described term " Tranylcypromine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula X
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " paroxetine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula Y
1Be dead key, and described structure
Replaced by hydrogen.
Described term " betahistine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula Z
1Be methyl, and described structure
Replaced by hydrogen.
Described term " amlodipine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula AA
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " hexahydrodesoxyephedrine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula BB
1Be methyl, and described structure
Replaced by hydrogen.
Described term " Rimantadine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula CC
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " decarboxylation loratadine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula DD
1Be dead key, and described structure
Replaced by hydrogen.
Described term " aniline " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula EE
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " leoponex " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula FF
1Be dead key, and described structure
Replaced by hydrogen.
Described term " dorzolamide " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula GG
1Be ethyl, and described structure
Replaced by hydrogen.
Described term " hydrogen chlorobenzene thiophene pyridazine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula HH
1Be dead key, and described structure
Replaced by hydrogen.
Described term " lisinopril " refers to a kind of pharmacological activity reagent, and wherein Q is by described structural formula II-1 (R
1Be hydrogen) or II-2 (R
1Be dead key) expression, and described structure
Replaced by hydrogen.
Described term " lomefloxacin " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula JJ
1Be dead key, and described structure
Replaced by hydrogen.
Described term " melphalan " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula KK
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " Nepafenac " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula LL
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " lyrica " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula MM
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " Riluzole " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula NN
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " valacyclovir " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula OO-1 and OO-2
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " Transbroncho " refers to a kind of pharmacological activity reagent, and wherein Q is by described structural formula PP-1 (R
1Be hydrogen) or PP-2 (R
1Be dead key) expression, and described structure
Replaced by hydrogen.
Described term " aminoglutethimide " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula QQ
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " amoxycilline Trihydrate bp " refers to a kind of pharmacological activity reagent, and wherein Q is represented by described formula R R, R
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " Ampicillin Trihydrate " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula SS
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " amrinone " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula TT
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " baclofen " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula UU
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " benazepril " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula VV
1Be dead key, and described structure
Replaced by hydrogen.
Described term " Bupropion " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula WW
1Be dead key, and described structure
Replaced by hydrogen.
Described term " Ciprofloxacin " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula XX
1Be dead key, and described structure
Replaced by hydrogen.
Described term " dapsone " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula YY
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " diclofenac " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula ZZ
1Be dead key, and described structure
Replaced by hydrogen.
Described term " enoxacin " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula AAA
1Be dead key, and described structure
Replaced by hydrogen.
Described term " Tibutol " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula BBB
1Be dead key, and described structure
Replaced by hydrogen.
Described term " gabapentin " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula CCC
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " Vasoxyl " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula DDD
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " midodrine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula EEE
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " Ritalin " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula FFF
1Be dead key, and described structure
Replaced by hydrogen.
Described term " norepinephrine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula GGG
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " pseudoephedrine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula HHH
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " Ramipril " refers to a kind of pharmacological activity reagent, and wherein Q is represented by described structural formula II I, R
1Be dead key, and described structure
Replaced by hydrogen.
Described term " Sertraline " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula JJJ
1Be methyl, and described structure
Replaced by hydrogen.
Described term " SB 209509 " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula KKK
1Be methyl, and described structure
Replaced by hydrogen.
Described term " cinacalcet " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula LLL
1Be dead key, and described structure
Replaced by hydrogen.
Described term " benzoctamine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula MMM
1Be methyl, and described structure
Replaced by hydrogen.
Described term " hydroxyl amphetamines " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula NNN
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " isometheptene " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula OOO
1Be methyl, and described structure
Replaced by hydrogen.
Described term " Euspirol " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula PPP
1Be methyl, and described structure
Replaced by hydrogen.
Described term " Dopamine HCL " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula OOO
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " Symmetrel " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula SSS
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " U.S. dollar amine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula TTT
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " metoclopramide " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula UUU
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " hexosamine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula VVV
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " afloqualone " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula WWW
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " aminohippuric acid " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula XXX
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " aminosallcylic acid " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula YYY
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " amodiaquine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula ZZZ
1Be dead key, and described structure
Replaced by hydrogen.
Described term " amsacrine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula AAAA
1Be dead key, and described structure
Replaced by hydrogen.
Described term " Ah's prednylidene 21-diethylaminoacetatte " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula BBBB
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " Quinacrime " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula CCCC
1Be dead key, and described structure
Replaced by hydrogen.
Described term " benzocaine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula DDDD
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " bumetanide " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula EEEE
1Be dead key, and described structure
Replaced by hydrogen.
Described term " Thiabutazide " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula FFFF
1Be dead key, and described structure
Replaced by hydrogen.
Described term " carbutamide " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula GGGG
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " carvedilol " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula HHHH-1 or HHHH-2
1Be dead key, and described structure
Replaced by hydrogen.
Described term " cefaclor " refers to a kind of pharmacological activity reagent, and wherein Q is represented by described structural formula II II, R
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " S 578 " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula JJJJ
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " cefroxadine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula KKKK
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " Cephradine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula LLLL
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " chlordiazepoxide " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula MMMM
1Be dead key, and described structure
Replaced by hydrogen.
Described term " chloroprocaine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula NNNN
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " clortermine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula OOOO
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " ciclacillin " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula PPPP
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " cyclopenthiazide " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula QQQQ
1Be dead key, and described structure
Replaced by hydrogen.
Described term " seromycin " refers to a kind of pharmacological activity reagent, and wherein Q is represented by described formula R RRR, R
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " mercaptamine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula SSSS
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " Wy-16225 " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula TTTT
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " dobutamine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula UUUU
1Be dead key, and described structure
Replaced by hydrogen.
Described term " eflornithine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula VVVV-1 or VVVV-2
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " racephedrine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula WWWW
1Be dead key, and described structure
Replaced by hydrogen.
Described term " suprarenin " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula XXXX
1Be dead key, and described structure
Replaced by hydrogen.
Described term " epirubicin " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula YYYY
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " she is for forint " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula ZZZZ
1Be dead key, and described structure
Replaced by hydrogen.
Described term " Phenfluoramine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula AAAAA
1Be dead key, and described structure
Replaced by hydrogen.
Described term " flucytosine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula BBBBB
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " Tecramine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula CCCCC
1Be dead key, and described structure
Replaced by hydrogen.
Described term " Furosemide " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula DDDDD
1Be dead key, and described structure
Replaced by hydrogen.
Described term " L-glutamic acid " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula EEEEE
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " glutamine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula FFFFF
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " gsh " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula GGGGG
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " glycine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula HHHHH
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " histamine " refers to a kind of pharmacological activity reagent, and wherein Q is by described structural formula II III-1 (R
1Be hydrogen) or IIIII-2 (R
1Be dead key) expression, and described structure
Replaced by hydrogen.
Described term " hydralazine " refers to a kind of pharmacological activity reagent, and wherein Q is by described structural formula JJJJJ-1 (R
1Be hydrogen) or JJJJJ-2 (R
1Be dead key) expression, and described structure
Replaced by hydrogen.
Described term " hydrochlorothiazide " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula KKKKK
1Be dead key, and described structure
Replaced by hydrogen.
Described term " idarubicin " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula LLLLL
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " imipenum " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula MMMMM-1 or MMMMM-2
1Be dead key, and described structure
Replaced by hydrogen.
Described term " iopanoic acid " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula NNNNN
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " isocaine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula OOOOO
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " Racemic isoproterenol " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula PPPPP
1Be dead key, and described structure
Replaced by hydrogen.
Described term " Xuprin " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula QQQQQ
1Be dead key, and described structure
Replaced by hydrogen.
Described term " restraining him orders " refers to a kind of pharmacological activity reagent, and wherein Q is represented by described formula R RRRR, R
1Be dead key, and described structure
Replaced by hydrogen.
Described term " Lamivudine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula SSSSS
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " lamotrigine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula TTTTT-1 or TTTTT-2
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " levodopa " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula UUUUU
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " lofexidine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula VVVVV
1Be dead key, and described structure
Replaced by hydrogen.
Described term " mecamylamine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula WWWWW
1Be dead key, and described structure
Replaced by hydrogen.
Described term " vialidon " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula XXXXX
1Be dead key, and described structure
Replaced by hydrogen.
Described term " mephentermine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula YYYYY
1Be dead key, and described structure
Replaced by hydrogen.
Described term " metaraminol " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula ZZZZZ
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " methyldopa " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2A
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " metirosine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2B
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " neamine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2C
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " fluorinacid " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2D
1Be dead key, and described structure
Replaced by hydrogen.
Described term " nimodipine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2E
1Be dead key, and described structure
Replaced by hydrogen.
Described term " nomefensine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2F
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " Nylidrine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2G
1Be dead key, and described structure
Replaced by hydrogen.
Described term " oxamniquine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2H
1Be dead key, and described structure
Replaced by hydrogen.
Described term " oxyfedrine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2I
1Be dead key, and described structure
Replaced by hydrogen.
Described term " perhexiline " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2J
1Be dead key, and described structure
Replaced by hydrogen.
Described term " phenmetrazine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2K
1Be dead key, and described structure
Replaced by hydrogen.
Described term " Phenylpropanolamine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2L
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " phyenlephrinium " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2M
1Be methyl, and described structure
Replaced by hydrogen.
Described term " pipemidic acid " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2N
1Be dead key, and described structure
Replaced by hydrogen.
Described term " piperazine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2O
1Be dead key, and described structure
Replaced by hydrogen.
Described term " pipradrol " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2P
1Be dead key, and described structure
Replaced by hydrogen.
Described term " pramipexole " refers to a kind of pharmacological activity reagent, and wherein Q is by described structural formula 2Q-1 (R
1Be dead key) or 2Q-2 (R
1Be hydrogen) expression, and described structure
Replaced by hydrogen.
Described term " primaquine " refers to a kind of pharmacological activity reagent, and wherein Q is by described structural formula 2R-1 (R
1Be hydrogen) or 2R-2 (R
1Be dead key) expression, and described structure
Replaced by hydrogen.
Described term " procainamide " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2S
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " Procarbazine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2T-1 or 2T-2
1Be dead key, and described structure
Replaced by hydrogen.
Described term " Pyrimethamine hcl " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2U-1 or 2U-2
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " quinethazone " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2V
1Be dead key, and described structure
Replaced by hydrogen.
Described term " sisomicin " refers to a kind of pharmacological activity reagent, and wherein Q is by described structural formula 2W-1 (R
1Be dead key), 2W-2 (R
1Be hydrogen), 2W-3 (R
1Be hydrogen).2W-4 (R
1Be hydrogen) and 2W-5 (R
1Be hydrogen) expression, and described structure
Replaced by hydrogen.
Described term " Sparfloxacin " refers to a kind of pharmacological activity reagent, and wherein Q is by described structural formula 2X-1 (R
1Be dead key) or 2X-2 (R
1Be hydrogen) expression, and described structure
Replaced by hydrogen.
Described term " spectinomycin " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2Y
1Be dead key, and described structure
Replaced by hydrogen.
Described term " sulfacitine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2Z
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " suladimethoxydiazine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2AA
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " Sulphadoxine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2BB
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " Sulphaguanidine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2CC-1 or 2CC-2
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " sulfaguanole " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2DD
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " sulfamethoxypyridazine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2EE
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " Sulfametoxydiazine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2FF
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " sulfamerazine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2GG
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " sulfamethazine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2HH
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " methylene sulfonamide thiadiazoles " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2II
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " Sulfamethomidine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2JJ
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " sulfisomezole " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2KK
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " sulfanilamide (SN) Sulfafurazole " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2LL
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " N1-monoacetyl sulfisoxazole " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2MM
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " sulfanilamide (SN) CS61 " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2NN
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " Tamsulosin " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2OO
1Be dead key, and described structure
Replaced by hydrogen.
Described term " terbutaline " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2PP
1Be dead key, and described structure
Replaced by hydrogen.
Described term " thiamphenicol " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2QQ
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " timonacic " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2RR
1Be dead key, and described structure
Replaced by hydrogen.
Described term " tinoridine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2SS
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " tizanidine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2TT-1 or 2TT-2
1Be dead key, and described structure
Replaced by hydrogen.
Described term " tolazoline " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2UU
1Be dead key, and described structure
Replaced by hydrogen.
Described term " tretoquinol " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2VV
1Be dead key, and described structure
Replaced by hydrogen.
Described term " Urocaudol " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2WW
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " trichlormethiazide " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2XX
1Be dead key, and described structure
Replaced by hydrogen.
Described term " trientine " refers to a kind of pharmacological activity reagent, and wherein Q is by described structural formula 2YY-1 (R
1Be hydrogen) or 2YY-2 (R
1Be dead key) expression, and described structure
Replaced by hydrogen.
Described term " trimethoprim " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2ZZ
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " trimetrexate " refers to a kind of pharmacological activity reagent, and wherein Q is by described structural formula 2AAA-1 or 2AAA-2 (R
1Be hydrogen) expression, and described structure
Replaced by hydrogen.
Described term " tromethane azoles " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2BBB
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " troxipide " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2CCC
1Be dead key, and described structure
Replaced by hydrogen.
Described term " tryptophane " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2DDD
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " zalcitabine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2EEE
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " clinic effect of alendronate " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2FFF
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " L-Ala " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2GGG
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " arginine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2HHH-1 or 2HHH-2
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " asparagine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2III
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " aspartic acid " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2JJJ
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " halfcystine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2KKK
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " L-glutamic acid " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2LLL
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " Histidine " refers to a kind of pharmacological activity reagent, and wherein Q is by described structural formula 2MMM-1 (R
1Be hydrogen), 2MMM-2 (R
1Be dead key), 2MMM-3 (R
1Be dead key) expression, and described structure
Replaced by hydrogen.
Described term " Isoleucine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2NNN
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " leucine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2OOO
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " Methionin " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2PPP
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " methionine(Met) " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2QQQ
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " phenylalanine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2RRR
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " proline(Pro) " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2SSS
1Be dead key, and described structure
Replaced by hydrogen.
Described term " Serine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2TTT
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " Threonine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2UUU
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " tyrosine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2VVV
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " Xie Ansuan " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2WWW
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " Deferoxamine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2XXX
1Be dead key, and described structure
Replaced by hydrogen.
Described term " the wheat salad is bright " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2YYY
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " phentolamine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2ZZZ
1Be dead key, and described structure
Replaced by hydrogen.
Described term " VitB1 " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2AAAA
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " adefovir ester " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2BBBB
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " adenosine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2CCCC
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " Alatrofloxacin " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2DDDD
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " Allan sodium phosphate " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2EEEE
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " perhexiline maleate " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2FFFF
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " almotriptan " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2GGGG
1Be dead key, and described structure
Replaced by hydrogen.
Described term " Lotronex " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2HHHH
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " amifostine " refers to a kind of pharmacological activity reagent, and wherein Q is by described structural formula 2IIII-1 (R
1Be hydrogen) or 2IIII-2 (R
1Be dead key) expression, and described structure
Replaced by hydrogen.
Described term " ketone valeric acid " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2JJJJ
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " amlexanox " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2KKKK
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " amprenavir " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2LLLL
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " anagrelide " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2MMMM
1Be dead key, and described structure
Replaced by hydrogen.
Described term " A Keer is fixed " refers to a kind of pharmacological activity reagent, and wherein Q is by described structural formula 2NNNN-1 (R
1Be hydrogen), 2NNNN-2 (R
1Be dead key) or 2NNNN-3 (R
1Be dead key) expression, and described structure
Replaced by hydrogen.
Described term " A Rui smooth " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2OOOO-1 or 2OOOO-2
1Be dead key, and described structure
Replaced by hydrogen.
Described term " argatroban " refers to a kind of pharmacological activity reagent, and wherein Q is by described structural formula 2PPPP-1 (R
1Be hydrogen) or 2PPPP-2 (R
1Be dead key) expression, and described structure
Replaced by hydrogen.
Described term " atovaquone " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2QQQQ
1Be dead key, and described structure
Replaced by hydrogen.
Described term " brimonidine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2RRRR-1 or 2RRRR-2
1Be dead key, and described structure
Replaced by hydrogen.
Described term " Bromfenac " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2SSSS
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " Cabergoline " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2TTTT
1Be dead key, and described structure
Replaced by hydrogen.
Described term " Candesartan " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2UUUU-1 or 2UUUU-2
1Be dead key, and described structure
Replaced by hydrogen.
Described term " carbidopa " refers to a kind of pharmacological activity reagent, and wherein Q is by described structural formula 2VVVV-1 (R
1Be hydrogen) or 2VVVV-2 (R
1Be dead key) expression, and described structure
Replaced by hydrogen.
Described term " Cefditoren pivoxil Cephalosporins " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2WWWW
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " cidofovir " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2XXXX
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " cisapride " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2YYYY
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " clofarabine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2ZZZZ
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " colestipol " refers to a kind of pharmacological activity reagent, and wherein Q is by described structural formula 2AAAAA-1 (R
1Be hydrogen) or 2AAAAA-2 (R
1Be dead key) or 2AAAAA-3 (R
1Be dead key) expression, and described structure
Replaced by hydrogen.
Described term " conivaptan " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2BBBBB
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " cytosine arabinoside " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2CCCCC
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " La Luosi " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2DDDDD-1 or 2DDDDD-2
1Be dead key, and described structure
Replaced by hydrogen.
Described term " Delavirdine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2EEEEE-1 or 2EEEEE-2
1Be dead key, and described structure
Replaced by hydrogen.
Described term " dexmedetomidine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2FFFFF
1Be dead key, and described structure
Replaced by hydrogen.
Described term " right Methylphenidylacetate " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2GGGGG
1Be dead key, and described structure
Replaced by hydrogen.
Described term " removes the hydroxyl glycosides " and refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2HHHHH
1Be dead key, and described structure
Replaced by hydrogen.
Described term " agit " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2IIIII
1Be dead key, and described structure
Replaced by hydrogen.
Described term " dolasetron " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2JJJJJ
1Be dead key, and described structure
Replaced by hydrogen.
Described term " Doxazosin " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2KKKKK
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " Dx " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2LLLLL
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " emtricitabine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2MMMMM
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " enalapril " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2NNNNN
1Be dead key, and described structure
Replaced by hydrogen.
Described term " felodipine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2OOOOO
1Be dead key, and described structure
Replaced by hydrogen.
Described term " epinastine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2PPPPP
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " erlotinib " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2QQQQQ
1Be dead key, and described structure
Replaced by hydrogen.
Described term " ertapenem " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2RRRRR
1Be dead key, and described structure
Replaced by hydrogen.
Described term " omeprazole " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2SSSSS
1Be dead key, and described structure
Replaced by hydrogen.
Described term " R-ETODOLAC " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2TTTTT
1Be dead key, and described structure
Replaced by hydrogen.
Described term " Famciclovir " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2UUUUU
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " famotidine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2VVVVV-1 or 2VVVVV-2
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " Fenoldopam " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2WWWWW
1Be dead key, and described structure
Replaced by hydrogen.
Described term " fomepizole " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2XXXXX
1Be dead key, and described structure
Replaced by hydrogen.
Described term " fosamprenavir " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2YYYYY
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " Gatifloxacin " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 2ZZZZZ
1Be dead key, and described structure
Replaced by hydrogen.
Described term " ganciclovir " refers to a kind of pharmacological activity reagent, and wherein Q is by described structural formula 3A-1 (R
1Be hydrogen) or 3A-2 (R
1Be dead key) expression, and described structure
Replaced by hydrogen.
Described term " Gefitinib " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 3B
1Be dead key, and described structure
Replaced by hydrogen.
Described term " gemcitabine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 3C
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " gemifloxacin " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 3D
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " Ge Lapasha star " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 3E
1Be dead key, and described structure
Replaced by hydrogen.
Described term " imatinib " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 3F
1Be dead key, and described structure
Replaced by hydrogen.
Described term " Imiquimod " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 3G
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " Irb " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 3H-1 or 3H-2
1Be dead key, and described structure
Replaced by hydrogen.
Described term " Isrodipine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 3I
1Be dead key, and described structure
Replaced by hydrogen.
Described term " Levothyroxine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 3J
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " gonadotropin " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 3K
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " amino-laevulic acid methyl esters " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 3L
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " metformin " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 3M
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " mitoxantrone " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 3N-1 or 3N-2
1Be dead key, and described structure
Replaced by hydrogen.
Described term " moexipril " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 3O
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " naratriptan " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 3P
1Be dead key, and described structure
Replaced by hydrogen.
Described term " Nelzarabine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 3Q
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " Moxifloxacin " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 3R
1Be dead key, and described structure
Replaced by hydrogen.
Described term " nicardipine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 3S
1Be dead key, and described structure
Replaced by hydrogen.
Described term " nisoldipine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 3T
1Be dead key, and described structure
Replaced by hydrogen.
Described term " nizatidine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 3U-1 or 3U-2
1Be dead key, and described structure
Replaced by hydrogen.
Described term " olanzapine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 3V
1Be dead key, and described structure
Replaced by hydrogen.
Described term " Oseltamivir " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 3W
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " olmesartan medoxomill " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 3X-1 or 3X-2
1Be dead key, and described structure
Replaced by hydrogen.
Described term " oxaliplatin " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 3Y
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " Pamidronic Acid " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 3Z
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " pantoprazole " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 3AA
1Be dead key, and described structure
Replaced by hydrogen.
Described term " pemetrexed disodium " refers to a kind of pharmacological activity reagent, and wherein Q is by described structural formula 3BB-1 (R
1Be hydrogen), 3BB-2 (R
1Be dead key) or 3BB-3 (R
1Be dead key) expression, and described structure
Replaced by hydrogen.
Described term " Penciclovir " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 3CC
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " pergolide " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 3DD
1Be dead key, and described structure
Replaced by hydrogen.
Described term " perindopril " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 3EE
1Be dead key, and described structure
Replaced by hydrogen.
Described term " Propafenone " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 3FF
1Be dead key, and described structure
Replaced by hydrogen.
Described term " quinapril " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 3GG
1Be dead key, and described structure
Replaced by hydrogen.
Described term " rabeprazole " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 3HH
1Be dead key, and described structure
Replaced by hydrogen.
Described term " Ranitidine HCL " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 3II-1 or 3II-2
1Be dead key, and described structure
Replaced by hydrogen.
Described term " risatriptan " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 3JJ
1Be dead key, and described structure
Replaced by hydrogen.
Described term " sevelamer " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 3KK
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " Virga " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 3LL
1Be dead key, and described structure
Replaced by hydrogen.
Described term " sumatriptan " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 3MM
1Be dead key, and described structure
Replaced by hydrogen.
Described term " tacrine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 3NN
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " Tadalafil (Cialis) " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 3OO
1Be dead key, and described structure
Replaced by hydrogen.
Described term " Tegaserod " refers to a kind of pharmacological activity reagent, and wherein Q is by described structural formula 3PP-1 (R
1Be hydrogen), 3PP-2 (R
1Be dead key), 3PP-3 (R
1Be dead key) expression, and described structure
Replaced by hydrogen.
Described term " tenofovir " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 3QQ
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " terazosin " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 3RR
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " Tigecycline " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 3SS
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " Tirofiban " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 3TT
1Be dead key, and described structure
Replaced by hydrogen.
Described term " torasemide " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 3UU
1Be dead key, and described structure
Replaced by hydrogen.
Described term " Trolapril " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 3VV
1Be dead key, and described structure
Replaced by hydrogen.
Described term " trovafloxacin azoles " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 3WW
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " valacyclovir " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 3XX-1 or 3XX-2
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " valganciclovir " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 3YY-1 or 3YY-2
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " valsartan " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 3ZZ-1 or 3ZZ-2
1Be dead key, and described structure
Replaced by hydrogen.
Described term " Vardenafil " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 3AAA
1Be dead key, and described structure
Replaced by hydrogen.
Described term " zalcitabine " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 3BBB
1Be hydrogen, and described structure
Replaced by hydrogen.
Described term " zolmitriptan " refers to a kind of pharmacological activity reagent, and wherein Q represents R by described structural formula 3CCC-1 or 3CCC-2
1Be dead key, and described structure
Replaced by hydrogen.
In another embodiment, described pharmacological activity reagent, QH, be to be selected from least a in the group of forming by following reagent: cholinergic (being also referred to as vagusstoff) reagent, adrenergic (being also referred to as suprarenin) reagent, norepinephrine energy (being also referred to as norepinephrine) reagent, dopaminergic reagent, serotonergic (being also referred to as serotonin) reagent, L-glutamic acid energy reagent, gamma amino butyric acid (GABA) energy (γ-An Jidingsuan) reagent, histamine energy reagent (for example, HTMT, amthamine, immepip, and the Alpha-Methyl histamine (Tocris, Ellisville, MO)), oxidase inhibitor, catechol-O-methyl transferase (COMT) (COMT) inhibitor, beta-secretase inhibitors, gamma-secretase inhibitors, potassium channel antagonists, calcium channel blocker (for example, nimodipine), the Adenosine Receptors conditioning agent, the cannabis receptor modulators (for example, virodhamine), improving brain function nootropics (that is, cognitive function promotes reagent) (for example, Sha's phenol acid amides, Minaprine, indeloxazine), nervosa peptide pathway modulators, neurotrophy reagent (promptly, a kind of can inducing neural the reagent of unit's cell growth), phosphodiesterase (PDE) IV inhibitor, Phosphoric acid esterase/calcineurin inhibitor, carbonic anhydrase inhibitor (for example, Bu Linzuo amine, dorzolamide), acceptor transportation conditioning agent, the trace amine receptor conditioning agent, the ζ receptor modulators, imidazoline receptor conditioning agent, sodium/calcium exchange retarding agent (being also referred to as agent of sodium ion calcium ion-exchanged or NCX), angiotensin-converting enzyme (ACE) inhibitor, antioxidant and on-steroidal AID (NSAID).
Described pharmacological activity reagent, QH can also be a kind of trace amine neurotransmitters, octopamine for example, tyrasamine, perhaps tryptamines.
Here employed " reagent " refers to a kind of like this compound, and it can generate a kind of physics, chemistry or biological effect with pungency (for example, a kind of activation reagent) or inhibition (for example, a kind of retardance reagent).Having irritating reagent can be agonist.Reagent with inhibition can be antagonist or inverse agonist.Inverse agonist is such compound, thereby the activity that it can go to regulate receptor activation acts on described acceptor in a kind of mode opposite with agonist.Therefore, be exposed to a kind of agonist in or use a kind of agonist and compare, be exposed in a kind of inverse agonist or use a kind of inverse agonist and can produce replying of weakening.
Cholinergic agents can be, for example, a kind of compound that can stimulate the effect of described vagusstoff, thus mediate two intercellular cell signals (a kind of cholinergic activator) by the vagusstoff mediation.Can releasing stimulus by following effects, for example, promote combining of vagusstoff and cell surface receptor, disturb the degraded of vagusstoff, stimulate the release of vagusstoff, stimulate the synthetic of vagusstoff, second messenger (for example, Phospholipase C, 1 of mediation vagusstoff cell signal, 4,5-triphosphoric acid Inositol nf12 99, protein kinase C, protein kinase A) activation, the variation of the ion in the target cell (for example, sodium, potassium) passage.Described reagent can also for these active any one or multiplely suppress or stop (for example, cholinergic antagonist).
Hydrolytic action by compound of the present invention, a kind of amine that is released out can become a kind of pharmacological activity reagent, described pharmacological activity reagent one or two in can described two the vagusstoff subclass of specific influence, described vagusstoff subclass is muscarinic type cholinergic receptor and nicotine type nicotinic cholinergic receptor, thereby hits a kind of specific acceptor subclass that can mediate specific biological procedures.In one embodiment, described cholinergic agents is selected from the muscarinic type cholinergic agonist (article of delivering in CNS Drugs " central nervous system class medicine " 3:467-481 in nineteen ninety-five referring to people such as Cutler N.R.; The article that Korczyn A.D. delivered in Drugs " pharmacology " 9:2259-2267 in 2000, be taught in this complete being introduced into as a reference in the above-mentioned article), muscarinic type cholinergic receptor antagonist, the nicotine type nicotinic cholinergic agonist, nicotine type nicotinic cholinergic receptor antagonist, acetylcholinesterase depressant, cholinergic antagonist, the allosteric modulators of cholinergic receptor and open channel retarding agent.
Muscarinic type cholinergic agonist or antagonist can mediate effect in various tissues, and wherein said tissue comprises individual unstriated muscle, cardiac muscle, exocrine gland and neural system.Nicotine type nicotinic cholinergic agonist or antagonist can mediate effect equally, realize this mediation to effect by neural biology, physics or the chemical ingredients that changes in nervous center, peripheral nervous system or autonomic neuromuscular function and the central nervous system in the autonomic nervous system.
In another embodiment, by reacting with a kind of Pseudocholinesterase, compound generation hydrolysis of the present invention, caused a kind of generation of cholinergic agonist, described cholinergic agonist is selected from RJR2403 (methyl-(4-pyridin-3-yl-3-butenyl)-amine) (being also referred to as TC2403), A85380 (3-(azetidine-2-ylmethoxy)-pyridine), toxoids A, Ai Biba Supreme Being's pyridine (epibatidine) and Neonicotine (anabasine) (Tocris, Ellisville, MO); And TC1734 ([4-(5-isopropoxy-pyridin-3-yl)-1-methyl-3-butenyl]-methylamine) (referring to people such as Obinu M.C. in 2002 at Progress in Neuropsychopharmacol ﹠amp; The article of delivering among Biol.Psychiatry " the psychiatric progress of neuropsychopathy pharmacology and the biology " 26:913-918; People such as Obinu M.C. in 2003 at Internatl.J.Neuropyschopharamology " neuropsychopathy pharmacology international magazine " 3: the article of delivering in the supplementary issue 1 (S361); The article that people such as Gatto G. delivered in CNS Drug Reviews " medicine for central nervous system is learned and looked back " 10:147-166 in 2004).
In another embodiment, by reacting with a kind of Pseudocholinesterase, compound generation hydrolysis of the present invention has caused a kind of generation of adrenergic reagent, and described adrenergic reagent is selected from α (for example, α
1, α
2) receptor stimulant, β (for example, β
1, β
2, β
3) receptor stimulant, α receptor antagonist and beta receptor antagonist.Described adrenergic reagent can be regulated adrenergic involved on neurone and acceptor, and can regulate being subjected to suprarenin any neuronal function or hormone function mediation or that influence.Because norepinephrine can play a role via α acceptor and beta receptor equally, described pharmacological activity reagent can influence the biology relevant with norepinephrine, chemistry or physical process.In another embodiment, described adrenergic reagent is a kind of primary amine or secondary amine.Adrenergic reagent comprises at least a reagent that is selected from down in the group: oxymetazoline, cirazoline, clonidine catapresan, A61603, agmatine, BRL 37344, and BRL 44408, special sieve of Zeeman, dobutamine, elfazepam, HEAT, ICI 118551, and ICI 89406, ICL 215001, and the Asia reaches azoles and looses, procaterol, and RX 821002, SB206606, SR 59230A, WB 4101, xamoterol, ZD 7114, and elfazepam and clenbuterol (Tocris, Ellisville, MO); And suprarenin, brimonidine, and dipivefrine.
In another embodiment, for example by reacting with a kind of Pseudocholinesterase, compound generation hydrolysis of the present invention, caused a kind of generation of norepinephrine energy reagent, described norepinephrine energy reagent is selected from noradrenaline reuptake inhibitor and norepinephrine release reagent.Described noradrenaline reuptake inhibitor can stop or reduce the separation of the norepinephrine in the cynapse, thereby increases the dosage of the norepinephrine in the described cynapse.The interception that separation produced for norepinephrine can be (for example, by blocking involved a kind of cell processes in the absorption again) or passive (for example, by the stablizing norepinephrine) of active.Described norepinephrine reagent can cause the release of norepinephrine from cell (for example, neurocyte, secretory cell, epithelial cell).Other compounds that are called as " reuptake inhibithors " and " release reagent " here play a role in a similar fashion, but it has specificity for specific pharmacological activity reagent, and wherein said pharmacological activity reagent is neurotransmitters for example.Described noradrenaline reuptake inhibitor can be, for example, and viloxazine, and/or nisoxetine (Tocris, Ellisville, MO); Maprotiline, tomoxetine, MCI 225 (hydrochloric acid 4-(2-fluoro-phenyl)-6-methyl-2-piperazine-1-base-thieno-[2,3-d] pyrimidine), oxaprotiline, Reboxetine, Talopram, Talsupram, and sulfo-nisoxetine; And amoxapine, desmethylimipramine, Ritalin, nomefensine, nortriptyline, and protriptyline (Sigma Chemical Co., St.Louis, MO).
In a kind of further embodiment, for example by reacting with a kind of Pseudocholinesterase, compound generation hydrolysis of the present invention, caused a kind of generation of serotonergic reagent, described serotonergic reagent is selected from serotonin antagonist, combination of serotonin agonist, thrombotonin reuptake inhibithors and thrombotonin release reagent.Described serotonergic reagent can, for example, affect the nerves and transmit or influence the release of hormone from incretory gland.Serotonergic reagent can comprise and is selected from least a in the following reagent: quipazine, anpirtoline, N-(4-Brombenzyl)-5-methoxytryptamine, BW723C86,5-formamido-tryptamines, m-CPP, N-Norclozapine, Rac-Desmethylcitalopram, isamoltane, L-694247, MDL 72832, MDL 73005EF, Alpha-Methyl-serotonin, 2-methyl-serotonin, Mi Sailin, MK212,5-oxygen in ninth of the ten Heavenly Stems primary colours amine, 6-nitro quipazine, fluoxetine, paroxetine, RS 67333, and RS 67506, RS 23597-190, RS 39604, and RU 24969, Sertraline, Desmethylsertraline, SR 57227, TFMPP, and fluvoxamine (Tocris, Ellisville, MO); And MMAI, RS 17017 (hydrochloric acid 1-(4-amino-5-chloro-2-methoxyl group-phenyl)-5-piperidines-1-base-penta-1-ketone), RS 66331, SB 271046 ((4-methoxyl group-3-piperazine-1-base-phenyl)-amino-5-chloro-3-methyl-benzo [b] thiophene-2-sulfonic acid), SB 399885, and SL65.0155 (hydrochloric acid (5-(8-amino-7-chloro-2,3-dihydro-benzo [1,4] Dioxins-5-yl)-and 3-(1-styroyl-piperidin-4-yl)-3H-[1,3,4] oxadiazoles-2-ketone).
In another embodiment, for example by reacting with a kind of Pseudocholinesterase, compound generation hydrolysis of the present invention, caused a kind of generation of L-glutamic acid energy reagent, described L-glutamic acid can be selected from N-methylaspartic acid (NMDA) receptor stimulant by reagent, N-methylaspartic acid receptor antagonist, N-methylaspartic acid glycine site agonist, N-methylaspartic acid glycine site antagonist, alpha-amino group-3-hydroxy-5-methyl base-4-isoxazolyl propionic acid (AMPA) receptor stimulant and alpha-amino group-3-hydroxy-5-methyl base-4-isoxazolyl propionic acid receptor antagonist, kainate receptor agonist and kainate receptor antagonist.In addition, perhaps can select, described L-glutamic acid can comprise N-methylaspartic acid ion channel modulators by reagent, N-methylaspartic acid polyamines site agonist, N-methylaspartic acid polyamines site antagonist, alpha-amino group-3-hydroxy-5-methyl base-4-isoxazolyl propionic acid/extra large people's alginic acid agonist, alpha-amino group-3-hydroxy-5-methyl base-4-isoxazolyl propionic acid/extra large people's alginic acid antagonist, I organizes metabotropic glutamate receptor agonists, I organizes metabotropic glutamate receptor antagonists, II organizes metabotropic glutamate receptor agonists, II organizes metabotropic glutamate receptor antagonists, and III organizes metabotropic glutamate receptor agonists, and III organizes metabotropic glutamate receptor antagonists, Quisqualic Acid responsive type AP6 site agonist, Quisqualic Acid responsive type AP6 site antagonist and excitatory amino acid absorption inhibitor.The example of metabotropic glutamate receptor compound comprises 2-methyl-6-(phenylacetylene base)-pyridine (MPEP), trans ACPD (anti-form-1-amino-1,3-pentamethylene dicarboxylic acid), ACPT-I, ACPT-II, ACPT-III, tADA, AIDA, AP3, AP4, AP5, AP6, (2R, 4R)-APDC, APICA, 3-carboxyl-4-hydroxy phenyl glycine, 4-carboxyl-3-hydroxy phenyl glycine, 4-carboxyl phenyl glycine, L-CCG-I, CHPG, CPPG, 1-cysteine sulfinic acid, DCG IV, 3,4-DCPG, 3,5-DHPG, E4CPG, EGLU, L-3 ' F2CCG-I, 1-L-glutamic acid, homoAMPA, 3-hydroxy phenyl glycine, ibotenic acid, LY 307452, and LY 341495, LY 367385, MAP4, MCCG, MCPG, MPPG, MSOP, MSPG, MTPG, Alpha-Methyl-3-carboxymethyl phenylglycocoll, o-phosphoric acid-1-Serine, PPG, Quisqualic Acid, s-sulfuric acid-1-halfcystine, UBP 1112, and spaglumic Acid (Tocris, Ellisville, MO).Other glutamate receptor compound comprises lamotrigine, Riluzole, and Salsolinol-1-carboxylic acid (Tocris, Ellisville, MO).
N-methylaspartic acid reagent can comprise aspartic acid, D-seromycin, ACBC, trans-ACBC, cis-ACPD, AP4, AP5, AP7, aspartic acid, 4-carboxyl phenyl glycine, CGP 37849, and CGP 39551, CGS 19755, CGP78608, and clo takes Pueraria lobota, CPP, L-cysteine sulfinic acid, L-glutamic acid, glycine, HA-996, N-(4-hydroxy phenyl ethanoyl) spermine, N-(4-hydroxy phenyl propyl alcohol) spermine, ibotenic acid, L689560, LY 235959, and MK 801, N-methylaspartic acid (NMDA), SDZ 220-040, SDZ 220-581, d-Serine, (tetrazolium-5-yl) glycine, U.S. dollar amine, spermine and spermidine (Tocris, Ellisville, MO); And Symmetrel (Sigma Chemical Co., St.Louis, MO).Alpha-amino group-3-hydroxy-5-methyl base-4-isoxazolyl propionic acid/extra large people's alginic acid reagent can comprise the L-Quisqualic Acid, domoic acid, people from sea alginic acid, alpha-amino group-3-hydroxy-5-methyl base-4-isoxazolyl propionic acid (AMPA), ATPA, CFM-2, (S)-CPW 399,5-fluorouracil L-Ala (5-fluorowillardiine), 5-iodouracil L-Ala (5-iodowillardiine), willardin (willardiine), GAMS, GYKI, 52466, IDRA 21, SYM 2081, and SYM 2206 (Tocris, Ellisville, MO).
Described excitatory amino acid absorption inhibitor can be dihydro people from sea alginic acid, cis-ACBD, L-CCG-II, clo takes Pueraria lobota, dihydro people from sea alginic acid, Soviet Union-3-hydroxyl aspartic acid, Soviet Union-3-methyl L-glutamic acid, MPDC, trans-2,4-PDC, SYM 2081, and TBOA (Tocris, Ellisville, MO).
Described N-methylaspartic acid receptor antagonist can be U.S. dollar amine (Tocris, Ellisville, MO) (article of delivering in Neuropharmacol. " neuropharm " 38:735-767 in 1999 referring to people such as Parsons C.G., being taught in this complete be introduced into as a reference in the above-mentioned article).Described N-methylaspartic acid Glycine Receptors agonist can be D-seromycin (Sigma ChemicalCompany, St.Louis, MO) (article of delivering among the 72:158-168 at Neurobiol.Learing Mem. " neurobiology aspect study and the memory " in 1999 referring to people such as Land C., being taught in this complete be introduced into as a reference in the above-mentioned article).
In a kind of further embodiment, for example by reacting with a kind of Pseudocholinesterase, compound generation hydrolysis of the present invention, caused a kind of generation of gamma amino butyric acid energy (GABAergic) reagent, described gamma amino butyric acid can be selected from the gaba receptor antagonist by reagent, gamma amino butyric acid energy receptor stimulant, Benzodiazepine site agonist, Benzodiazepine site antagonist, Benzodiazepine site inverse agonist and gamma amino butyric acid absorption inhibitor.Described gamma amino butyric acid can be able to comprise, for example, and pantherine (muscimol), baclofen, Sa chlorophenol, 1-amino-5-bromouracil, CACA, CGP 35348 ((3-amino-propyl group)-diethoxymethyl-Hypophosporous Acid, 50), CGP 46381 ((3-amino-propyl group)-cyclohexyl methyl-Hypophosporous Acid, 50), CGP 52432, and CGP 54626, and CGP 55845, gamma amino butyric acid (GABA), GBLD 345,2-hydroxyl Sa chlorophenol, isoguvacine, phaclofen, SB 205384, and SCH 50911, SKF 97541, TACA THIP, TPMPA, and tracazolate (Tocris, Ellisville, MO); SR 95531 and SGS 742 ((3-amino-propyl group)-butyl-Hypophosporous Acid, 50) (article of delivering in J.Ong.Pharmac.Ther. " tumor pharmacother magazine " 67:187-246 in nineteen ninety-five referring to people such as Kerr D.I.B.; The article that people such as Froestl W. delivered in Biochem.Pharmacol. " biological chemistry pharmacy " 68:1479-1487 in 2004).
In another embodiment, for example by reacting with a kind of Pseudocholinesterase, compound generation hydrolysis of the present invention has caused a kind of generation of dopaminergic reagent, and described dopaminergic reagent is selected from the group of being made up of following reagent place: the dopaminergic antagonist, the dopaminergic agonist, the dopaminergic reuptake inhibithors, dopaminergic release reagent, and levodopa (L-DOPA) (3, the 4-Dihydroxyphenylalanine, 3-hydroxyl tyrosine).Because Dopamine HCL is the intermediate product in norepinephrine, suprarenin and the melanic building-up process, then can both produce a kind of physics, chemistry or biological effect to biological procedures to any reagent that Dopamine HCL exerts an influence, wherein said biological procedures is relevant with norepinephrine, suprarenin and melanochrome, and perhaps described biological procedures is mediated by norepinephrine, suprarenin and melanochrome.Described dopaminergic reagent can influence Dopamine HCL that exists as a kind of hormone or the Dopamine HCL that exists as a kind of neurotransmitters.Described dopaminergic reagent can comprise, for example, and dihydrexidine (dihydrexidine), A68930 (1-amino methyl-3-phenyl-heterochromatic full-5,6-glycol), SKF 38393, and AJ 76,4-phenyl-1,2,3, the 4-tetrahydroisoquinoline, and rimcazole (Tocris, Ellisville, MO); And A77636 (3-diamantane-1-base-1-amino methyl-heterochromatic full-5,6-glycol), adrogolide, and SKF 81297 (6-chloro-1-phenyl-2,3,4,5-tetrahydrochysene-1H-benzo [d] nitrogen Zhuo-7,8-glycol); Pergolide (Sigma Chemical Company, St.Louis, MO) and pramipexole (be also referred to as MIRAPEX
TM).
Here employed " conditioning agent " refers to a kind of compound that can regulate, adjust or adapt to a kind of biological pathway or receptor-mediated signal transduction pathway.Described conditioning agent can stimulate or suppress a kind of biological pathway or receptor-mediated signal transduction pathway.For example, a kind of Adenosine Receptors conditioning agent can strengthen the ability that adenosine combines with acceptor, weaken the ability that adenosine combines with acceptor, directly (for example combine with acceptor, a kind of agonist or inverse agonist) and react to described acceptor generation effect or with described acceptor, thereby the biological pathway relevant with Adenosine Receptors Mediated Signal Transduction approach regulated, adjusted or adapt to.
In another embodiment, for example by reacting with a kind of Pseudocholinesterase, compound generation hydrolysis of the present invention, caused being selected from the generation of at least a material in the group of forming by following substances: oxidase inhibitor, catechol-O-methyl transferase (COMT) (COMT) inhibitor, beta-secretase inhibitors or gamma-secretase inhibitors.
Described inhibitor has stoped enzyme to participate in biological procedures or has weakened the activity of the enzyme in biological procedures, for example, a kind of beta-secretase inhibitors or a kind of gamma-secretase inhibitors can stop in people's brain by starchiness precursor protein generation β-starchiness albumen.The proteic accumulation of β starchiness is relevant with human Alzheimer's disease.Therefore, the proteic minimizing of β starchiness can improve, prevents or reduce the outbreak or the deterioration of Alzheimer's disease.
In a kind of specific embodiment, described oxidase inhibitor is at least a following material that is selected from: the rasagiline (article of delivering in the Curr.Opin.Investig.Drugs current suggestion of medicine " research property " 3:794-979 in 2002 referring to Kupsch A., be taught in this complete being introduced into as a reference in the above-mentioned article), 1-(cumarone-2-yl)-2-propyl group aminopentane, 5-benzyloxy-2-indyl methylamine, lazabemide, CHF 3381 (2-(indane-2-base is amino)-ethanamide), milacemide, mofegiline, brofaromine, Ro-41-1049, RS-1636; And bifemelane, and tetrindol (Tocris, Ellisville, MO).
In another embodiment, for example by reacting with a kind of Pseudocholinesterase, compound generation hydrolysis of the present invention has caused a kind of generation of potassium channel blocking agent, and described potassium channel blocking agent is a 4-aminopyridine for example.Because the selective permeability of potassium channel is important for the static speech of the membrane potential of cell, then potassium-channel is blocked the unpolarizing that can strengthen or prolong film, thereby for example neuronic cell signal of increase.
Described pharmacological activity reagent can exert an influence to the cell in central nervous system, peripheral nervous system, autonomic nervous system and its hetero-organization (for example, unstriated muscle, cardiac muscle, skeletal muscle) and the organ (for example, incretory gland, exocrine gland).
In one embodiment, described pharmacological activity reagent can be a kind of exogenous agents (come from beyond the described individuality or beyond described individuality and generate).In another embodiment, described pharmacological activity reagent can a kind of endogenous (come from the described individuality or generate in described individuality) reagent, described endogenous reagent is that purifying comes out in the biological origin that obtains from described individuality.
Compound of the present invention can stimulate or suppresses described physics, chemistry or biological action, and after this, pharmacological activity reagent of the present invention may reside between two or more cells.In one embodiment, described two or more cells are two or more neurocyte (presynaptic neuron, postsynaptic neurons).Described neurocyte may reside in described central nervous system, peripheral nervous system or the autonomic nervous system.In another embodiment, described two or more cells can be at least one muscle cell (unstriated muscle, skeletal muscle, cardiac muscle) and at least one neurocyte (presynaptic neuron, postsynaptic neuron).In another embodiment, described two or more cells can be at least one neurocyte and at least one non-neuronal cell (for example, medulliadrenal secretory cell, exocrine gland or incretory gland cell, the epithelial cell of organ or tissue).Described two or more cells can be external cell (for example, cell culture) or intravital cells (for example, being present among the individuality).
Described pharmacological activity reagent can be a kind of improving brain function nootropics (that is, cognitive function promote reagent), a kind of neurotrophy preparation (that is a kind of reagent that can the cell growth of inducing neural unit) and/or neuroprotective reagent.
In another embodiment, the present invention is a kind of method that individuality is treated.Described method comprises to described individuality uses compound of the present invention.Described compound can suppress Pseudocholinesterase, and, pass through hydrolytic action, for example, by reacting with a kind of Pseudocholinesterase, become a kind of at least a component of pharmacological activity reagent, wherein said pharmacological activity reagent can be treated the illness of described individuality.
The described pharmacological activity reagent that discharges by compound of the present invention, QH is selected from least a in the group of being made up of following reagent place: cholinergic agents, adrenergic reagent, norepinephrine energy reagent, dopaminergic reagent, serotonergic reagent, L-glutamic acid energy reagent, gamma amino butyric acid (GABA) energy reagent, histamine energy reagent, oxidase inhibitor, catechol-O-methyl transferase (COMT) (COMT) inhibitor, beta-secretase inhibitors, gamma-secretase inhibitors, potassium channel antagonists, calcium channel blocker, the Adenosine Receptors conditioning agent, the cannabis receptor modulators, improving brain function nootropics, nervosa peptide pathway modulators, neurotrophy reagent, phosphodiesterase (PDE) IV inhibitor, Phosphoric acid esterase/calcineurin inhibitor, acceptor transportation conditioning agent and trace amine receptor conditioning agent.
Compound of the present invention can suppress the activity of Pseudocholinesterase, and this can utilize IC50 to represent.Here employed described term " IC50 " refers to its activity or effect and is suppressed 50% compound concentrations, for example, the means of the frequency by reducing reaction conditions, for example the forfeiture of memory or cognitive ability 50%; By means in conjunction with minimizing 50% with competitive molecule and albumen (for example, a kind of acceptor); Perhaps by means with active level (for example, the activity of Pseudocholinesterase) reduction by 50%.
Here employed " individuality " refers to any Mammals.Mammals can be a kind of rodent (for example rat, mouse, perhaps cavy), a kind of performing animal (for example dog or cat), a kind of ruminating animal (for example horse or ox) or a kind of primate (for example monkey or the mankind).A kind of preferred embodiment in, described individuality is human.
Can utilize described pharmacological activity reagent that the individuality of suffering from illness is treated.Described illness comprises at least a illness that is selected from the group that central nervous system disorders, peripheral nervous system illness and disorder of autonomic nervous system form.
In a kind of specific embodiment, the described individuality that uses compound of the present invention to treat suffers from central nervous system disorders.Here employed " central nervous system disorders " refers to the brain of the described individuality of influence or any disease or the minor illness of spinal cord.The central nervous system disorders possibility of using compound of the present invention to treat for example, is a kind of result of genetic diseases, or is exposed to the result in the secondary compound relevant with a kind of primary disease.Described central nervous system disorders can show as inappropriate neurotransmitters discharge, synthetic, handle, absorb again or cell signal, perhaps can be used as inappropriate neurotransmitters discharge, synthetic, handle, absorb again or the result of cell signal.Described central nervous system disorders can also be extra or can select show as inefficacy or inappropriate neuronic transmission, perhaps can be used as result inefficacy or inappropriate neuronic transmission, the inefficacy of this neuronic transmission is owing to the blocking-up of ionic channel.
In a kind of specific embodiment, use a kind of compound that described central nervous system disorders is treated, described compound comprises substituted this bright or substituted Physostigmine.Compound of the present invention can be used to following illness is treated, and comprising: dejected, and anxiety, and psychoactive compounds of the present invention can be used to Parkinson's disease, memory injury and cognitive function damage are treated.
Described memory injury can occur among the human individual.The memory injury that can utilize compound of the present invention to treat comprises Alzheimer's disease, the memory disappearance relevant with the age, memory is consolidated the damage of aspect, the short-term memory damage, the mild cognitive function damage, declarative memory damage and the memory injury relevant, the perhaps memory injury that produces as multiple sclerosis and/or Parkinsonian result with multiple sclerosis and/or Parkinson's disease.
The described memory injury that can utilize compound of the present invention to treat may be the result who contacts with the mAChR antagonist.In one embodiment, described mAChR antagonist is a coromegine.In another embodiment, described mAChR antagonist is a Scopolamine.In another embodiment, described mAChR antagonist is a tropine melate.
Thereby the mAChR antagonist comprises any material by the cell signal of vagusstoff mediation that takes place between the effect blocking-up presynaptic neuron that can block, weaken, weaken, suppress, hinder, limit, reduce, reduce, retrain or disturb described vagusstoff and the postsynaptic neuron.Described antagonist can, for example, by following mode the effect of vagusstoff is revolted: stop vagusstoff to combine with mAChR on being present in postsynaptic neuron, vagusstoff with stop vagusstoff mediation postsynaptic incident after mAChR combines, by being present in the degraded of the acetylcholinesterase interference vagusstoff in the synaptic cleft, perhaps disturb the release of vagusstoff from presynaptic neuron.
In another embodiment, compound of the present invention can be used to the peripheral nervous system illness of individuality is treated.Described peripheral nervous system illness is passable, for example, be by the disease that provides innerv neurone to cause for skeletal muscle or with the relevant disease of innerv neurone (for example, myasthenia gravis) is provided for skeletal muscle.Described peripheral nervous system illness can be, for example, and the damage aspect the neurone generation vagusstoff release at the neuromuscular function place of skeletal muscle, unstriated muscle or cardiac muscle.
Compound of the present invention can be used to treat individual disorder of autonomic nervous system (sympathetic nervous system, parasympathetic nervous system).Described disorder of autonomic nervous system can be the illness that can exert an influence to the unstriated muscle of internal organ, body of gland (incretory gland, exocrine gland), blood vessel or cardiac muscle.The disorder of autonomic nervous system that can utilize compound of the present invention to treat can be postoperative swelling and uroschesis.Described disorder of autonomic nervous system may be a kind of function damage relevant with autonomic nervous system, for example, the damage of norepinephrine release aspect from sympathetic neuron, the perhaps damage of vagusstoff release aspect from parasympathetic neuron, wherein said neurone is positioned at organ, blood vessel or gland cell (for example, epithelial cell, neurocyte, muscle cell, phoirocyte) in the cynapse.Those skilled in the art should have the ability the individuality of suffering from central nervous system disorders, peripheral nervous system illness and disorder of autonomic nervous system is diagnosed.
Here employed " memory injury or cognitive function damage " refers to weakening of human mind ability and/or weakening of the ability of cognitive process.Can utilize the technology set up described cognition and/or memory process and damage cognitive and/or the memory process are estimated or to be determined.For example, use compound of the present invention individuality is treated before, afterwards or be accompanied by the treatment of compound of the present invention, utilize one or more testing method of having set up well known to those skilled in the art that memory is estimated.Such testing method comprises that the passive avoidance test is (referring to Principles of Neuropsychopharmacology " neuropsychopathy pharmacology principle ", people such as Feldman R.S. delivered in 1997, Sinauer Assoc., Inc., Sunderland, MA is taught in this complete being introduced into as a reference in the above-mentioned article); (referring to L ' examen clinique enpsychologie, Rey A. delivered in 1964 Rey sense of hearing words and phrases learning tests (RAVLT), Paris:Presses Universitairesde France; A Wechsler Memory Scale " Wechsler Memory Scale "; WechslerMemory Scale-Revised " Wechsler Memory Scale-revised edition " (Wechsler D., Wechsler Memory Scale-Revised Manual " Wechsler Memory Scale-artificial revised edition ", NY, NY, The Psychological Corp.1987); California words and phrases learning test-second edition (article The Californian Verbal Learning Test " California words and phrases learning test " that delivered in 2000 referring to people such as Delis D.C., Second Edition (second edition), Adult Version (Adult Edition), Manual, SanAntonio, TX:The Psychological Corporation); Complete evaluation-the Wesnes of computerize of cognitive drug research (CDR); The Buschke selectivity is reminded test (article of delivering in Neurology " neurological " 24:1019-1025 in 1974 referring to people such as Buschke H.); Simple and easy visual space recall tests-revised edition; And daily attention test (article of delivering in Neuropsycholigia " nervosa psychology " 38:252-271 in 2000 referring to people such as Perry R.J.).
In a kind of specific embodiment, before using compound of the present invention, among or utilize a kind of word to recall test afterwards and the mankind's memory is estimated or determined, test recalled in wherein said word is Rey sense of hearing words and phrases learning test (RAVLT) for example.
In another embodiment, described invention described herein provides a kind of method for the treatment of individual neurological conditions.Described method comprises to described individuality uses compound of the present invention.Thereby described compound can suppress the neurological conditions that Pseudocholinesterase is treated described individuality.Described compound via hydrolysis reaction, for example, by reacting with described Pseudocholinesterase, becomes a kind of at least a component of pharmacological activity reagent, and it can further treat the neurological conditions of described individuality.Described pharmacological activity reagent, QH, can, for example, keeping inhibition for described Pseudocholinesterase, wherein said Pseudocholinesterase is subjected to the inhibition of compound of the present invention.Described pharmacological activity reagent can further be treated described neurological conditions, for example, by compound being delivered to neurone or cynapse, keep neuronic polarized action, prevent the absorption again of neurotransmitters, the mode that stimulates or keep the synthetic of neurotransmitters or discharge.
In a kind of specific embodiment, use the central nervous system disorders of compounds for treating individuality of the present invention.Thereby described compound can acetylcholine esterase inhibition be treated the central nervous system disorders of described individuality.Described compound via hydrolysis reaction, for example, by reacting with described acetylcholinesterase, becomes a kind of at least a component of pharmacological activity reagent, and it can further treat the central nervous system disorders of described individuality.
A kind of further embodiment among the present invention is a kind of method that increases the vagusstoff in the external sample.Described method comprises to described external sample uses a kind of compound.Described compound can suppress Pseudocholinesterase, thereby increases the vagusstoff in the described external sample.Described compound via hydrolysis reaction, for example, by reacting with described Pseudocholinesterase, becomes a kind of at least a component of pharmacological activity reagent, and it can further increase the Pseudocholinesterase in the described external sample.
Described external sample can be a kind of not celliferous sample or the sample that contains cell.The cell that is contained can be mammalian cell (for example, recombinant human erythropoietin (CHO) cell), insect cell or bacterial cell.Described method can be used to estimate the ability that described compound suppresses Pseudocholinesterase before individuality is used, and the ability of described pharmacological activity agents influence biology, chemistry or material process.Described method can be packed and be packed in the test kit, as the detection method of screening compound of the present invention, detects the pharmacological activity of the reagent that cholinesterase activity and described compound generate by hydrolytic action.
Another embodiment among the present invention is a kind of method that increases the vagusstoff in the tissue.Described method comprises to described tissue uses compound of the present invention.Described compound can suppress Pseudocholinesterase, thereby increase the vagusstoff in the described tissue, and via hydrolysis reaction, for example, by reacting with described Pseudocholinesterase, become a kind of at least a component of pharmacological activity reagent, it can further increase the Pseudocholinesterase in the described tissue.
Described tissue can be a kind of nervous tissue, muscle tissue (cardiac muscle, skeletal muscle, unstriated muscle) or collect be selected from any one or multiple types of organization in the group of forming by following tissue: nervous tissue, muscle tissue, epithelium and reticular tissue.Described tissue can be separated (being separated from described individuality).
Another embodiment among the present invention is a kind of method that increases the vagusstoff in the individuality.Described method comprises to described individuality uses compound of the present invention.Described compound can suppress Pseudocholinesterase (for example, acetylcholinesterase, butyrylcholine esterase), thereby increases vagusstoff.Described compound for example, by reacting with described Pseudocholinesterase, becomes a kind of at least a component of pharmacological activity reagent via hydrolysis reaction, and it can further increase the Pseudocholinesterase in the described individuality.
In one embodiment, described pharmacological activity reagent can increase the vagusstoff in the central nervous system of described individuality.In another embodiment, described pharmacological activity reagent can increase the vagusstoff in the peripheral nervous system of described individuality.In another embodiment, use compound of the present invention and can increase the vagusstoff in the autonomic nervous system of described individuality.Be used for to the technology that the increase of the vagusstoff in external sample, tissue and the individuality is estimated be well known to those skilled in the art (referring to, for example, the article that people such as Day J.C. delivered in Methods " method " 23:21-39 in calendar year 2001 is taught in this complete being introduced into as a reference in the above-mentioned article).
The further increase of described vagusstoff can be so a kind of increase, it is by the increase that mediates with the similar mode of compound mediated increase (inhibition of acetylcholinesterase) of the present invention, or for example release by increasing vagusstoff, increases the synthetic of vagusstoff or prevent that the mode of the deactivation of vagusstoff from carrying out the increase of vagusstoff.
In a kind of further embodiment, the present invention is a kind of method that increases the transmission between two or more neurones.Described method comprises described neurone is contacted with compound of the present invention.Described compound can suppress Pseudocholinesterase, thereby increases the transmission between described two or more neurones.Compound of the present invention via hydrolysis reaction, for example, by reacting with described Pseudocholinesterase, becomes a kind of at least a component of pharmacological activity reagent, and it can further increase the transmission between described two or more neurones.
The further increase of described transmission can be, for example, the similar mode of the mode of action (by suppressing Pseudocholinesterase) with a kind of and compound of the present invention increases, perhaps increase by any other modes by described pharmacological activity reagent mediation, for example excite nerve and transmit plain release or synthetic, suppress the absorption again of neurotransmitters, change neuronic ionic channel.
Can increase external transmission or the interior transmission of body between two or more neurones.Be used for determining that the technology of the increase of transmission in external transmission and the body is well known to those skilled in the art.For example, can use electrophysiological method to write down the variation of the unpolarizing of described postsynaptic neuron.
Compound of the present invention can increase transmission between two or more neurones by following manner, for example, (for example increases the neurotransmitters that are present in the described cynapse, cholinergic, adrenergic, norepinephrine energy, dopaminergic, serotonergic, L-glutamic acid energy, gamma amino butyric acid energy, histamine energy) dosage or weaken or the degraded that stops described neurotransmitters (for example, by suppressing monoamine oxidase, catechol-O-methyl transferase (COMT)).In addition, perhaps can select, compound of the present invention can be by (for example regulating the neurotransmitters acceptor, Adenosine Receptors, the cannabis acceptor, trace amine receptor) or the mode of the ionic channel (for example, potassium channel, sodium channel) of retardance in the neurone increase transmission between two or more neurones.Further, compound of the present invention can increase transmission between two or more neurones by following manner: suppress phosphodiesterase (PDE) IV, Phosphoric acid esterase/calcineurin inhibitor or adjusting acceptor transport molecules, suppress phosphodiesterase or Phosphoric acid esterase, (for example perhaps regulate the acceptor transport molecules, BARK, arrestin, E3 ubiquitin ligase).
The increase of the transmission in the individuality can reduce or alleviate central nervous system disorders or peripheral nervous system illness, for example memory injury and cognitive function damage.For example, the increase of the cholinergic transmission among the human individual (for example, postsynaptic) can reduce or alleviate the symptom relevant with Alzheimer's disease.The increase of the dopaminergic transmission among the human individual (for example, postsynaptic) can reduce or alleviate the symptom relevant with Parkinson's disease.Compound of the present invention can via with the hydrolytic action of Pseudocholinesterase, become, for example, a kind of dopaminergic reagent, described reagent can increase the transmission (presynaptic or postsynaptic) in the central nervous system of suffering from Parkinsonian human individual, thereby the selectivity substitute of a kind of L-DOPA (levodopa) is provided.For example, the lipotropy phenylcarbamic acid salt of compound of the present invention can promote the infiltration of described compound in hemato encephalic barrier, thereby allows to carry out sending of pharmacological activity reagent, particularly, and in described central nervous system.Those skilled in the art can utilize the technology of having set up, and determine that described pharmacological activity reagent is for the effect that the human individual produced of suffering from central nervous system disorders or peripheral nervous system illness.
Another embodiment among the present invention is a kind of method for the treatment of individual cholinergic disappearance.Described method comprises to described individuality uses compound of the present invention.Thereby compound of the present invention can suppress the cholinergic disappearance that Pseudocholinesterase is treated described individuality.Compound of the present invention via hydrolysis reaction, for example, by reacting with described Pseudocholinesterase, becomes a kind of at least a component of pharmacological activity reagent, and it can further treat the cholinergic disappearance of described individuality.Further treatment can be, for example, and by the mode of acetylcholine esterase inhibition and/or butyrylcholine esterase, perhaps by increasing the release or the synthetic mode of vagusstoff.
Described cholinergic disappearance may be a kind of neural system disappearance.For example, can use compound of the present invention that the human individual who suffers from Alzheimer's disease is treated.In Alzheimer's disease, presynaptic neuron takes place to degenerate fast, this makes along with deterioration of described disease, and the effect of Pseudocholinesterase inhibition is limited (article of delivering in CNS Drugs " medicine for central nervous system " 3:467-481 in nineteen ninety-five referring to people such as Cutler N.R.).In suffering from the individuality of Alzheimer's disease, Pseudocholinesterase continues to be present in the described synapse, is hydrolyzed for any a spot of vagusstoff that may be present in the described cynapse.Therefore, compound of the present invention can become a kind of cholinergic agonist, thereby improve described cholinergic disappearance by increasing the cynapse transmission that mediates by vagusstoff in the individual central nervous system, wherein said individuality suffers from Alzheimer's disease, mild cognitive function damage, the memory injury relevant with the age, the memory disappearance relevant with the age, weather aging, vascular dementia, lewy body disease dementia and/or Parkinson's disease.
In another embodiment, the present invention is a kind of method for the treatment of individual memory injury.Described method comprises to described individuality uses compound of the present invention.Thereby described compound can suppress the memory injury that Pseudocholinesterase is treated described individuality.Described compound via hydrolysis reaction, for example, by reacting with described Pseudocholinesterase, becomes a kind of at least a component of pharmacological activity reagent, and it can further treat the memory injury of described individuality.The further treatment of carrying out for memory can be and the similar methods of treatment of compound of the present invention, or the methods of treatment of carrying out in the mode different with compound of the present invention, and it is a feature with described pharmacological activity reagent.
Described memory injury can be the memory injury that is selected from the group of being made up of following damage: memory is consolidated the damage of aspect, the damage of long-term memory and the damage of short-term memory.Those skilled in the art should have the ability the individuality of suffering from memory injury is discerned, and described damage is estimated.
In a kind of specific embodiment, the human individual suffer from be selected from the group that following disease forms in the relevant memory injury of a kind of illness: Alzheimer's disease, Parkinson's disease, the lethe relevant, mild cognitive function damage and multiple sclerosis with the age.
In another embodiment, the described human individual who utilizes compound of the present invention to treat suffers from the decline of the cognitive function relevant with the age.
A kind of further embodiment among the present invention is a kind of to the method for organizing the delivery of pharmacologically active agent.Described method comprises to described tissue uses compound of the present invention.Compound of the present invention can suppress Pseudocholinesterase and, by hydrolytic action, for example, by reacting with described Pseudocholinesterase, become a kind of at least a component of pharmacological activity reagent, thereby described pharmacological activity reagent is delivered in the described tissue.
Described tissue can be a kind of vitro tissue sample or can be a kind of in-vivo tissue (being present within the individuality).Described tissue can be a muscle tissue, the combination arbitrarily in nervous tissue or muscle tissue, nervous tissue, reticular tissue or the epithelium.Can utilize compound of the present invention delivery of pharmacologically active agent in tissue, have Pseudocholinesterase at the most proximal end or the distal-most end place of described tissue, described Pseudocholinesterase is subjected to the inhibition of compound of the present invention.For example, can utilize compound of the present invention in muscle tissue, to send a kind of pharmacological activity reagent, for example cholinergic agents.Combination can take place with Pseudocholinesterase (acetylcholinesterase, butyrylcholine esterase) in compound of the present invention, thus suppress the active of described Pseudocholinesterase and, by hydrolytic action (for example, being hydrolyzed), become a kind of cholinergic agents with Pseudocholinesterase.Described pharmacological activity reagent may be delivered in a kind of muscle cell, described muscle cell is positioned at the most proximal end of the binding site of compound of the present invention and described Pseudocholinesterase, and perhaps described pharmacological activity reagent is delivered to the muscle cell of the distal-most end that is arranged in above-mentioned binding site.Similarly, described compound can combine with the Pseudocholinesterase in being present in neural neurone, and cholinergic agents is delivered to the most proximal end or the distal-most end of described binding site.
Compound of the present invention can combine with Pseudocholinesterase, and via hydrolytic action, for example, by reacting, thereby send following substances, for example: dopaminergic reagent to the most proximal end of the binding site that is arranged in compound of the present invention or the neurone of distal-most end with described Pseudocholinesterase, serotonergic reagent, adrenergic reagent, norepinephrine energy reagent, L-glutamic acid energy reagent, gamma amino butyric acid (GABA) energy reagent, histamine energy reagent, oxidase inhibitor, catechol-O-methyl transferase (COMT) (COMT) inhibitor, beta-secretase inhibitors, gamma-secretase inhibitors, potassium channel antagonists, calcium channel blocker, the Adenosine Receptors conditioning agent, the cannabis receptor modulators, improving brain function nootropics, nervosa peptide pathway modulators, neurotrophy reagent, phosphodiesterase (PDE) IV inhibitor, Phosphoric acid esterase/calcineurin inhibitor, acceptor transportation conditioning agent or trace amine receptor conditioning agent.Therefore, compound of the present invention provides a kind of method to described central nervous system delivery of pharmacologically active agent.Described pharmacological activity reagent can diffuse to each zone of brain and mediate their effect.
The present invention includes a kind of method for the treatment of individual illness, treat by using compound of the present invention, wherein said illness is a kind of neurological conditions, be selected from delayed gastric emptying, note damaged many moving obstacles (ADHD), phobia, somnopathy, apoplexy, insane, pain, anticholinergic agents is excessive, and tobacco relies on, Parkinson's disease, memory injury, and cognitive function damage.The present invention includes compound of the present invention and be used to make the purposes of pharmaceutical preparation, described pharmaceutical preparation is used for the treatment of individual illness, and wherein said illness is a kind of neurological conditions, be selected from delayed gastric emptying, note damaged many moving obstacles (ADHD), phobia, somnopathy, apoplexy, insane, pain, anticholinergic agents is excessive, and tobacco relies on, Parkinson's disease, memory injury, and cognitive function damage.
The present invention includes a kind of method for the treatment of individual illness, treat by using compound of the present invention, wherein said illness is selected from glaucoma, the tumour illness, delayed gastric emptying is noted damaged many moving obstacles (ADHD), phobia, apoplexy, multiple sclerosis, somnopathy, insane, pain, anticholinergic agents is excessive, and tobacco relies on, cardiovascular disorder is hypertension for example, infectation of bacteria, Meniere's disease, virus infection, allergy, and spasticity.The present invention includes compound of the present invention and be used to make the purposes of pharmaceutical preparation, described pharmaceutical preparation is used for the treatment of individual illness, and wherein said illness is selected from glaucoma, the tumour illness, delayed gastric emptying, note damaged many moving obstacles (ADHD), phobia, apoplexy, multiple sclerosis, somnopathy, insane, pain, anticholinergic agents is excessive, tobacco relies on, and cardiovascular disorder is hypertension for example, infectation of bacteria, Meniere's disease, virus infection, allergy, and spasticity.
In one embodiment, the present invention includes a kind of method for the treatment of individual illness, treat by using compound of the present invention, wherein said illness is selected from delayed gastric emptying, note damaged many moving obstacles (ADHD), phobia, somnopathy, apoplexy, insane, pain, anticholinergic agents is excessive, and tobacco relies on.The present invention includes compound of the present invention and be used to make the purposes of pharmaceutical preparation, described pharmaceutical preparation is used for the treatment of individual illness, wherein said illness is selected from delayed gastric emptying, notes damaged many moving obstacles (ADHD), phobia, somnopathy, apoplexy, insane, pain, anticholinergic agents is excessive, and tobacco relies on.
In one embodiment, the present invention includes a kind of method for the treatment of individual illness, treat by using compound of the present invention, wherein said illness is that anticholinergic agents is excessive.The present invention includes compound of the present invention and be used to make the purposes of pharmaceutical preparation, described pharmaceutical preparation is used for the treatment of individual illness, and wherein said illness is that anticholinergic agents is excessive.
In one embodiment, the method that the present invention includes above to be discussed, wherein said individuality is human.
Compound of the present invention can be used to the form of single dose or multiple doses in method of the present invention, pharmaceutical composition, test kit and the detection method.Described multiple doses form can be to use with multiple dosage in one day, use in single per daily dose more than one day time, use every day and continue time with multiple dosage, perhaps carry out using of single dose and the fate that is accompanied by at certain intervals carries out using of multiple doses at given fate more than one day.Described multiple doses form can every day, a couple of days, weekly, several weeks, every month, several months, every year or several years use.
In method of the present invention, can use compound of the present invention to individuality with acute (temporary transient or short-term) or the mode of chronic (persistent or secular).For example, can in the individual method of treatment, use compound of the present invention, use compound of the present invention to described individuality with following frequency: once a day, every day repeatedly (for example, 2 times, 3 times, 4 times), continue one day, a couple of days, one week, several weeks, one month, several months or several years.
In one embodiment, the dosage of compound of the present invention can be about 0.1 milligram, about 1 milligram, and about 2.5 milligrams, about 5 milligrams, about 10 milligrams, about 15 milligrams, about 20 milligrams, about 25 milligrams, about 40 milligrams, about 50 milligrams, about 75 milligrams, about 90 milligrams, about 100 milligrams, about 150 milligrams, about 200 milligrams, about 250 milligrams, about 500 milligrams, about 750 milligrams or about 1000 milligrams.
In another embodiment, the dosage of compound of the present invention can be between about 1 milligram to about 100 milligrams; Between about 2 milligrams to about 50 milligrams; Perhaps between about 5 milligrams to about 25 milligrams.
In another embodiment, every kind of dosage in the described multiple doses form can be about 0.1 milligram, about 1 milligram, about 2.5 milligrams, about 5 milligrams, about 10 milligrams, about 20 milligrams, about 25 milligrams, about 40 milligrams, about 50 milligrams, about 75 milligrams, about 90 milligrams, about 100 milligrams, about 150 milligrams, about 200 milligrams, about 250 milligrams, about 500 milligrams, about 750 milligrams or about 1000 milligrams.
In a kind of further embodiment, every kind of dosage in the described multiple doses form can be between about 1 milligram to about 100 milligrams; Between about 2 milligrams to about 50 milligrams; Perhaps between about 5 milligrams to about 25 milligrams.
Compound of the present invention and described pharmacological activity reagent are applied in the method for the present invention with a kind of effective dosage or are used in detection of the present invention and the test kit.When described term " effective dose ", when " effectively ... dosage " or " treatment effective dose " is used to refer to the amount of compound of the present invention or pharmacological activity reagent, it is defined as being enough to produce the described compound of treatment effect or the amount or the dosage of pharmacological activity reagent (for example, is enough to treat the amount of individual neurological conditions; Be enough to increase the amount that is present in the vagusstoff in external sample, tissue or the individuality; Be enough to increase the amount of the transmission between two or more neurones; Be enough to treat the amount of cholinergic disappearance; Be enough to treat the amount of memory injury; Be enough to treat the amount of cognitive function damage; Be enough to pharmacological activity reagent is delivered to amount in tissue or the individuality).
What compound of the present invention can be chosen wantonly together is used in method of the present invention, test kit and the detection method with a kind of acceptable carrier.Selection for acceptable carrier will be depended on described method, test kit or detection method.For example, in a kind of in vitro method, detection or test kit, acceptable carrier can be a physiological saline, suitable buffer reagent or cell culture medium.
Compound of the present invention can be used separately, perhaps use with the form of mixture with the vehicle of routine, described vehicle for example is, be fit to carry out to use in the intestines or pharmacology or the acceptable organic carrier material of physiology or the inorganic carrier material of parenteral applications, deleterious reaction can not take place with the compound that used in the described method in described material.The acceptable carrier of the medicine that is fit to comprises water, salts solution (for example Luo Geshi solution), and alcohol, oil, gelatin and carbohydrate be lactose for example, amylose starch or starch, fatty acid ester, Walocel MT 20.000PV, and polyvinylpyrrolidine.Such preparation can be aseptic and if necessary, can mix with auxiliary agent, described auxiliary agent is a lubricant for example, sanitas, stablizer, wetting agent, emulsifying agent is used to influence the salt of osmotic pressure, buffer reagent, tinting material, and/or fragrance matter, deleterious reaction can not take place with the compound that used in the method for the invention in them.When needs, described preparation also can make up with other active substance, is used for reducing metabolic degradation.
The preferred application process of compound of the present invention is Orally administered (for example tablet or capsule).Described compound can separately or make up the back with mixture and use in for some time with single dosage form or with the form more than single dose, thereby (for example give desired effect, improve neurological conditions, increase vagusstoff, increase the transmission between two or more neurones, treatment cholinergic disappearance, treatment memory injury, the damage of treatment cognitive function, the delivery of pharmacologically active agent).
Can use compound of the present invention in the target site place in individuality.Selection for described target site can be depended on the illness of receiving treatment.For example, in skeletal muscle (described target site), carry out local injection and can be used to treat the peripheral nervous system illness, perhaps in celiolymph, brain hole or the ventricles of the brain (target site), carry out local injection and can be used to treat central nervous system disorders.In another embodiment, can utilize a kind of eye dropping liquid, ointment, gel or ocular injection mode that contains described compound to treat individual glaucoma.
When needs carried out or expect to carry out parenteral application, the particularly suitable mixture that is used for described compound was injectable sterile solution, the preferred oil solution or the aqueous solution, and suspension, and milk sap, perhaps implant comprises suppository.Concrete, the carrier that is used to carry out parenteral administration comprises D/W, physiological saline, pure water, ethanol, glycerol, propylene glycol, peanut oil, sesame oil, polyoxyethylene block copolymer, and similar substrates.Ampoule is conventional unitary dose.The described compound that is used in method of the present invention, detection method or the test kit can also be directed in the liposome, perhaps uses by transdermal pump or transdermal patch.The medicinal mixture that is fit to use in the present invention is well known to those skilled in the art, and for example Pharmaceutical Sciences " pharmaceutical science " (the 17th edition, Mack Pub Co., Easton, PA) describe to some extent and among the WO 96/05309, be taught in this complete being introduced into as a reference in the above-mentioned article.
Dosage and the frequency (single dose or multiple doses) used to individuality can change according to various factors, comprise, for example, the described neurological conditions of receiving treatment, the type of the cholinergic disappearance of described individuality, the time length of described neurological conditions, the degree of described memory injury (for example, memory is consolidated the damage of aspect, the damage of short-term memory), the degree of described cognitive function damage (for example, attention, alertness is carried out function, wakefulness state, wake up with a start, warning property is carried out function, reaction times), need be sent or by cognitive pharmacological activity reagent; The size of described individuality, age, sex, healthy state, body weight, constitutional index and diet; The character and the degree of the symptom of described illness or memory injury or cognitive function damage, the kind of Synergistic treatment comes from the complication of described illness or damage, other problems relevant with health that the mankind had of perhaps receiving treatment.
Other treatment plan or treatment reagent can be united use with method of the present invention, perhaps together are used in the method for the present invention with compound of the present invention.Complete within those skilled in the art's limit of power for adjustment and operation that established dosage (for example, frequency and cycle) is carried out.
Representational compound of the present invention includes, but are not limited to:
According to following method compound of the present invention is estimated:
Utilize the modification method of people's such as Ellmann (be illustrated in 1961 in Biochem.Pharmacol. " biological chemistry pharmacy " 7:88-95, deliver article) colorimetric method, at 25 ℃ of acetylcholine esterase actives of determining compounds of the present invention down.Described enzyme, compound and damping fluid were cultivated 30 minutes in advance.When described pre-cultivation stage finishes, add described substrate vagusstoff.Contain the 10 milli Tris damping fluids (pH 8) that rub in the final detection mixed solution, 0.3 milli rub vagusstoff and 0.33 milli rub DTNB (5,5 ,-dithio two (2-nitrobenzoic acid)) and 0.08U/ milliliter enzyme.At each IC
50At least detect the described compound of five kinds of (5) different concns in the test.
Come the hydrolysis of indirect monitoring vagusstoff by the conjugation that forms between measurement thiocholine and DTNB.
In order to estimate the effect that amnesia produced that compound of the present invention brings out Scopolamine, during before rat being carried out the training of inhibition avoidance task 30 minutes, be rat injecting normal saline or Scopolamine Hydrochloride (0.75 mg/kg).After through described training test, immediately to rat injecting normal saline or compound.After 24 hours, estimate for the hold facility of this task in the rat that Scopolamine or physiological saline were handled.
According to the method for people such as Ellman GL described in the article of in Biochem.Pharmacol. " biological chemistry pharmacy " 7:88-95, delivering in 1961 and Nadarajah B in the article of in J.Anal.Toxicol. " analytical toxicology magazine " 16:192-193, delivering in 1992, the in-vitro screening of finishing compound of the present invention detects, and is taught in this complete being introduced into as a reference in above-mentioned two pieces of articles.
The described method of delivering in European Journal ofPharmacology " European pharmacology magazine " 187:193-199 in nineteen ninety according to people such as Freedman of article, determine the induction phenomena of the body temperature reduction that compound of the present invention produces, the content of above-mentioned article is hereby incorporated by.Determined that equally compound of the present invention provides required dosage range of cholinergic effect and time cycle.
The present invention further describes by following embodiment, and described embodiment is not construed as limiting in any form.
Embodiment
Embodiment 1: compound synthetic
Compound of the present invention is to utilize method known to those skilled in the art to carry out R
aThe linked reaction of-phenol and Q-H prepares.For example:
R wherein
aRepresent this bright suitable phenyl substituent, the bright or Physostigmine of Li Wasi for example, and a kind of pharmacological activity reagent that contains amine of Q representative.For example,
Exemplary compound is shown in the Table A.
Table A
| Initiator | Reagent/condition | The result |
| Desmethylimipramine (300 milligrams, 1.0 millis rub) Q=P R 1=methyl | In methylene dichloride (8 milliliters), utilize the bright carboxylamine imidazoles solution (2.0 millis rub 2.0 equivalents) of sodium bicarbonate and Li Wasi that desmethylimipramine is handled | 4 (240 milligrams, 52% productive rate, HPLC＞95%) separate by column chromatography |
| Fluvoxamine maleate (100 milligrams, 0.23 milli rubs) Q=S R 1=hydrogen | In methylene dichloride (7 milliliters), utilize the bright carboxylamine imidazoles solution (0.66 milli rubs 3.0 equivalents) of sodium bicarbonate and Li Wasi that fluvoxamine is handled | 8 (10 milligrams, 8% productive rate, HPLC purity 90%) separate by preparation type thin-layer chromatography |
| Fluoxetine Hydrochloride (100 milligrams, 0.29 milli rubs) Q=R R 1It is methyl | In methylene dichloride (6 milliliters), utilize the bright carboxylamine imidazoles solution (0.63 milli rubs 2.2 equivalents) of diisopropylethylamine (0.63 milli rubs 2.2 equivalents) and Li Wasi that fluoxetine is handled | 7, separate by preparation type thin-layer chromatography, obtain 30 milligrams of products, 20% productive rate, HPLC purity 80% |
| Two hydrochloric acid betahistines (400 milligrams, 1.9 millis rub) Q=Z R 1It is methyl | In methylene dichloride (6 milliliters), utilize the bright carboxylamine imidazoles solution (4.0 millis rub 4.2 equivalents) of diisopropylethylamine (4.0 millis rub 4.2 equivalents) and Li Wasi that betahistine is handled | 11HPLC has represented to obtain 16% target product |
| Paroxetine (87 milligrams, 0.26 milli rubs) Q=Y R 1It is dead key | Bright carboxylamine solution (the bright and carbonyl dimidazoles of the sharp gas of S-carries out coupling) 1.2 millis that are present in the Li Wasi in the methylene dichloride rub methylene dichloride (4 milliliters) | 9 (49 milligrams, purity 83%) |
| Ampicillin Trihydrate (150 milligrams, 0.43 milli rubs) Q=SS R 1Be hydrogen | In methylene dichloride (5 milliliters), utilize the bright carboxylamine imidazoles solution (1 milli rubs 2.5 equivalents) of diisopropylethylamine (2 millis rub 5.0 equivalents) and Li Wasi that the Ampicillin Trihydrate is handled | ??21 |
| Ampicillin Trihydrate (150 milligrams, 0.43 milli rubs) Q=SS R 1Be hydrogen | In methylene dichloride (5 milliliters), utilize diisopropylethylamine (2 millis rub 5.0 equivalents) and Physostigmine carboxylamine imidazoles solution (1 milli rubs 2.5 equivalents) that the Ampicillin Trihydrate is handled | ??22 |
| Toxilic acid Sertraline (250 milligrams, 0.73 milli rubs) Q=JJJ R 1It is methyl | In methylene dichloride (15 milliliters), under the existence of diisopropylethylamine (2.87 millis rub 3.9 equivalents), utilize the bright carboxylamine imidazoles solution (1.5 millis rub 2.05 equivalents) of sodium bicarbonate and Li Wasi that Sertraline is handled | ??23 |
| Toxilic acid Sertraline (250 milligrams, 0.73 milli rubs) Q=JJJ R 1It is methyl | In methylene dichloride (15 milliliters), under the existence of diisopropylethylamine (2.87 millis rub 3.9 equivalents), utilize sodium bicarbonate and Physostigmine carboxylamine imidazoles solution (1.5 millis rub 2.05 equivalents) that Sertraline is handled | ??24 |
| Dapsone (250 milligrams, 1 milli rubs) Q=YY R 1Be hydrogen | The bright carboxylamine solution of sharp gas (1 milli rubs), diisopropylethylamine (1.2 millis rub), methylene dichloride (9 milliliters) | ??25 |
| Dapsone (250 milligrams, 1 milli rubs) Q=YY R 1Be hydrogen | Physostigmine carboxylamine solution (1 milli rubs), diisopropylethylamine (1.2 millis rub), methylene dichloride (9 milliliters) | ??26 |
| Midodrine hydrochloride (125 milligrams, 0.4 milli rubs) Q=EEE R 1Be hydrogen | The bright carboxylamine solution of sharp gas (0.5 milli rubs), methylene dichloride (4 milliliters), diisopropylethylamine (1.2 millis rub) | ??27 |
| Midodrine hydrochloride (125 milligrams, 0.4 milli rubs) Q=EEE R 1Be hydrogen | Physostigmine carboxylamine solution (0.5 milli rubs), methylene dichloride (4 milliliters), diisopropylethylamine (1.2 millis rub) | ??28 |
| Baclofen (200 milligrams, 0.94 milli rubs) Q=UU R 1Be hydrogen | The bright carboxylamine solution of sharp gas (1.1 millis rub), methylene dichloride (7 milliliters), diisopropylethylamine (2.4 millis rub) | 19 (5%), urea derivative (26%) and two additional peaks |
| Two hydrochloric acid betahistines (418 milligrams, 2.0 millis rub) Q=Z R 1It is methyl | Utilize the normal sodium carbonate solution of 2.0M that betahistine is handled, dry and concentrate, in methylene dichloride with described carbamate solution (8 milliliters, 0.25M is present in the methylene dichloride), methylene dichloride (2 milliliters) | 11 from silicagel column purifying come out, under high vacuum, carry out drying |
| Amlodipine (410 milligrams, 1.0 millis rub) Q=AA R 1Be hydrogen | The bright carboxylamine solution (4 milliliters, 0.25M is present in the methylene dichloride) of sharp gas, methylene dichloride (6 milliliters) | 12 LC-MS chromatograms show described product quality consistent with described output (30%) |
| Hydrochloric acid Ritalin (270 milligrams, 1.0 millis rub) Q=FFF R 1It is dead key | 1) utilize the normal sodium carbonate solution of 2.0M that Ritalin is handled, dry and concentrated, utilize (2.4 milliliters of the bright carboxylamine solution of Li Wasi, 0.25M, be present in the methylene dichloride) handle, methylene dichloride (2 milliliters) 2) adds diisopropylethylamine (130 milligrams, 1.0 millis rub) and stirring | ??29 |
| Hydrochloric acid Ritalin (270 milligrams, 1.0 millis rub) Q=FFF R 1It is dead key | 1) utilize the normal sodium carbonate solution of 2.0M that Ritalin is handled, dry and concentrated, utilize (2.4 milliliters of Physostigmine carboxylamine solution, 0.25M, be present in the methylene dichloride) handle, methylene dichloride (2 milliliters) 2) adds diisopropylethylamine (130 milligrams, 1.0 millis rub) and stirring | ??30 |
| Gabapentin (100 milligrams, 0.58 milli rubs) Q=CCC R 1Be hydrogen | Chlorine trimethyl silane (0.58 milli rub), carbonyl dimidazoles (0.58 milli rubs), (S)-and the bright phenol (0.58 milli rubs) of Li Wasi, triethylamine (1.2 millis rub), acetonitrile (0.5 milliliter), trichloromethane, methylene dichloride (2.5 milliliters) | 31 use preparation HPLC to isolate 25 milligrams the target product and the trifluoroacetate of 21 milligrams of described target products |
| Protriptyline hydrochloride (2 grams, 6.67 millis rub) Q=U R 1It is methyl | Carbonyl dimidazoles (6.67 milli rub), (S)-the bright phenol (6.67 millis rub) of Li Wasi, diisopropylethylamine (10.0 millis rub), methylene dichloride (60 milliliters) | 6 on silicagel column through twice purifying, thereby obtain 1.15 the gram target products (HPLC purity＞99%) |
| Conjugation protriptyline (1.15 grams, 2.5 millis rub) | 1.0M the diethyl ether solution of hydrochloric acid (4.5 milliliters), trichloromethane (10 milliliters) | Isolate 1.21 gram described target products (HPLC purity＞99%) |
| Fluoxetine Hydrochloride (2 grams, 6 millis rub) Q=R R 1It is methyl | Carbonyl dimidazoles (6 milli rub), (S)-the bright phenol (6 millis rub) of Li Wasi, diisopropylethylamine (9 millis rub), methylene dichloride (40 milliliters) | 7 utilize silicagel column to carry out chromatogram purification, thereby obtain the target product (HPLC purity＞99%) of 1.05 grams |
| Conjugation fluoxetine (1.05 grams, 2.1 millis rub) | 1.0M the diethyl ether solution of hydrochloric acid (4.5 milliliters), trichloromethane (10 milliliters) | Isolate 970 milligrams of described target products (HPLC purity＞99%) |
| Duloxetine (740 milligrams, 2.5 millis rub) Q=T R 1It is methyl | Carbonyl dimidazoles (2.6 milli rub), (S)-the bright phenol (2.7 millis rub) of Li Wasi, methylene dichloride (10 milliliters) | ??10 |
| Fluvoxamine maleate (434 milligrams, 1 milli rubs) Q=S R 1=hydrogen | Carbonyl dimidazoles (1.05 milli rub), (S)-the bright phenol (1.1 millis rub) of Li Wasi, diisopropylethylamine (3 millis rub), methylene dichloride (6 milliliters) | The LC-MS colour scale of 8 described reaction mixtures shows the quality of described product |
| Fluvoxamine maleate (2.5 grams, 5.7 millis rub) Q=S R 1=hydrogen | Carbonyl dimidazoles (6.05 milli rub), (S)-the bright phenol (6.3 millis rub) of Li Wasi, diisopropylethylamine (17.3 millis rub), methylene dichloride (40 milliliters) | The LC-MS colour scale of 8 described reaction mixtures shows the quality of described product |
Embodiment 2: the preparation of hydrochloride
Embodiment 2A: with compound dissolution of the present invention (every milli rub compound use 3 milliliters of chloroforms) in chloroform.Under 0 ℃ to the diethyl ether solution that wherein dropwise adds 1M hydrochloric acid (1.5-2 molar equivalent).After the step of described adding hydrochloric acid is finished, described mixed solution is warming up to room temperature.Remove by evaporation and to desolvate and under vacuum condition, described resistates is carried out drying, thereby obtain the hydrochloride of described compound.
Embodiment 2B: with compound dissolution in water and use the normal sodium carbonate solution of 2.0M that pH is adjusted to about 10.Utilize methylene dichloride (2x30 milliliter) that described compound is extracted afterwards, drying (sodium sulfate) and concentrated.Described resistates by silicagel column, is used heptane (74%), and ethyl acetate (25%) and triethylamine (1%) are as described solvent.Use rotatory evaporator that described cut is evaporated, and under high vacuum condition dried overnight.Utilize water (6 milliliters) that described resistates is absorbed, add the hydrochloric acid (3 milliliters) of 2.0M subsequently.Afterwards with described solution freeze-drying, thereby obtain the described compound that exists with hydrochloride form.
Embodiment 3: the vitro inhibition of acetylcholinesterase:
The whole reagent that used in these trials all belong to the analytical pure rank.Iodo vagusstoff and 5,5 ,-dithio two (2-nitrobenzoic acids) (DTNB) and human recombinant acetylcholinesterase (C1682) all be that (St.Louis MO) locates to buy acquisition from for example Sigma Chemical Co.
Utilize the modification method of people's such as Ellmann (be illustrated in 1961 in Biochem.Pharmacol. " biological chemistry pharmacy " 7:88-95, deliver article) colorimetric method, at 25 ℃ of acetylcholine esterase actives of determining compounds of the present invention down.Described enzyme, compound and damping fluid were cultivated 30 minutes in advance.When described pre-cultivation stage finishes, add described substrate vagusstoff.Contain the 10 milli Tris damping fluids (pH 8) that rub in the final detection mixed solution, 0.3 milli rub vagusstoff and 0.33 milli rub DTNB (5,5 ,-dithio two (2-nitrobenzoic acid)) and 0.08U/ milliliter enzyme.At each IC
50At least detect the described compound of five kinds of (5) different concns in the test.
Come the hydrolysis of indirect monitoring vagusstoff by the conjugation that forms between measurement thiocholine and DTNB.Utilize the microwell plate spectrophotometer to note the optical density (OD) in 5 minutes time of 405 nanometers and draw at the curve of time.The inverse (inverse) of the initial rate of the inhibitor concentration within the specific limits of drawing is at the curve (Dixon Plot) of concentration, thereby obtains described IC
50Value (enzymic activity is suppressed 50% o'clock concentration), described IC
50Value is the logarithm (article of delivering in J.Chem.Ed. " chemical education magazine " 80:214-218 in 2003 referring to people such as Burlingham) of x y-intercept.
Described result is summarized as follows:
These data show that compound of the present invention can be at the vitro inhibition acetylcholinesterase.Compound of the present invention should be better than the bright for the restraining effect that acetylcholinesterase produced of this for the restraining effect that acetylcholinesterase produced, and described the bright of this is the bright of for example Li Wasi.Compare with the bright of this, have the activity of similar activity or rising by this bright synthetic compound.Therefore, this bright compound with known enzymic activity is carried out structural change, can not weaken or suppress described this bright enzymic activity.
Embodiment 4: the inhibition of Pseudocholinesterase in the brain:
Carry out intraperitoneal (i.p.) injection of the bright or compound of the present invention of Li Wasi to male Wistar rat.Observe the effect of the cholinergic behavior in the described animal.The head and the sharp separation that cut away animal after injecting 3 hours go out brain.Described cerebral tissue is cut into small pieces, be positioned over and utilize Polytron PT1200 hand-held to organize clarifixator (Kinematic AG) in 10 milliliters of ice-cold Tris, to carry out homogeneous on ice and immediately, contain 0.1% Triton-X and proteinase inhibitor among the wherein said Tris.The proteinase inhibitor that is present in the described extraction damping fluid is Antipain (10M), Aprotinin (5TIU/ milligram albumen), Bestatin (60 receive rub), Leupeptin (10M) and Pepstatin (1M).Final extent of dilution in the homogenate described in the final detection mixed solution is 120 times.
As mentioned above, utilize the modification method of people's such as Ellmann (be illustrated in 1961 in Biochem.Pharmacol. " biological chemistry pharmacy " 7:88-95, deliver article) colorimetric method, determine the gross activity of Pseudocholinesterase.Come the hydrolysis of indirect monitoring vagusstoff by the conjugation that forms between measurement thiocholine and DTNB.Utilize the microwell plate spectrophotometer to note the optical density (OD) in five (5) minutes time of 405 nanometers and draw at the curve of time.The slope meter of the linear portion by described graphic representation is calculated described initial rate.
Utilize the protein content in the described homogenate that the activity of Pseudocholinesterase is carried out normalization processing (normalized).The active ratio of the normal state Pseudocholinesterase of the rat of the activity of the normal state Pseudocholinesterase of the rat that utilization process control compound is handled or the rat of compound treatment of the present invention and the processing of process physiological saline can calculate relative cholinesterase activity.
Embodiment 5: in a plurality of tentative passive avoidances detect Scopolamine is brought out
The alleviation of amnesia
Inhibition is avoided and to be used to carry out the screening of cognitive function performance, and this is because the discrete character that described task had requires accurate pharmacology operation and has the ability that the information of learning was obtained, consolidated or recalled in optionally study.This task is widely used in estimates the central action medicine for facilitation that animal produced, wherein said animal is normal, undressed animal, and by using Scopolamine to produce letheral animal, described Scopolamine is a kind of muscarinic type cholinergic receptor antagonist, can form significant amnesia.
The device that the described inhibition that is used is in these trials avoided is made up of an exposure experiments to light case and a dark proofing box, and they interconnect by the mode of slide gate.Described training comprises: rat is positioned in the described exposure experiments to light case, allows the head of rat back to described door.After ten seconds, described sliding gate is opened, and noted the time of lag (latency) (the longest 100 seconds) that rat enters described dark proofing box.When rat entered described dark proofing box, it received the successive vola electric shock (0.4 milliampere) that produces via described metal grating floor, turns back to described exposure experiments to light case until it.By this order incident is continued to carry out to continue 100 seconds time of stop until described rat in described exposure experiments to light case, perhaps received maximum 5 times vola electric shocks until described rat.
After above-mentioned initial test 24 hours, carry out confining force test (retentiontest), perhaps test the ability that described rat remembers before to avoid at inhibition event in the device.Described rat is positioned in the described exposure experiments to light case, allows the head of rat back to described door.After ten seconds, described door is opened, allowed rat to enter described dark proofing box.In the confining force test, do not carry out the vola electric shock.Note time of lag (latency) (the longest 900 seconds) that rat enters described dark proofing box and with it as measuring to memory.
In order to estimate the effect that amnesia produced that compound of the present invention brings out for Scopolamine, 30 minutes before rat being carried out described inhibition avoidance task training to rat injecting normal saline or Scopolamine Hydrochloride (0.75 mg/kg).After described training test, give rat injecting normal saline or compound immediately.
After 24 hours,, the confining force of the task of the rat of handling through Scopolamine or physiological saline is estimated according to above described.Before the test of described confining force,, and in the confining force test, do not shock by electricity not to rat administered compound (medicine).In order to carry out the confining force test, described rat is positioned in the described exposure experiments to light case.After ten five seconds, door is opened automatically and is measured rat and enters the time of lag of described dark proofing box.Be its one-shot measurement for the memory of this task (primary measure) time of lag that rat enters described dark proofing box.In this scheme, compound of the present invention is estimated.By of bright (contrast) of endoperitoneal mode to rat injection compound and Li Wasi.Determine the most significant increase dosage of described time of lag, that is, the effective dose of every kind of compound, and under described most effective dose, performance for intac (physiological saline) control group, and with respect to the performance for (Scopolamine) group of damaged.
Embodiment 6: in-vitro screening
According to the method for people such as Ellman GL described in the article of in Biochem.Pharmacol. " biological chemistry pharmacy " 7:88-95, delivering in 1961 and Nadarajah B in the article of in J.Anal.Toxicol. " analytical toxicology magazine " 16:192-193, delivering in 1992, the in-vitro screening of finishing compound of the present invention detects, and is taught in this complete being introduced into as a reference in above-mentioned two pieces of articles.Described detection method is finished according to following condition:
| The source | Human recombinant HEK-293 cell |
| Substrate | 700 little vagusstoffs that rub |
| Solvent | 1% dimethyl sulfoxide (DMSO) |
| Pre-incubation time/temperature | 25 ℃ following 15 minutes |
| Incubation time/temperature | 25 ℃ following 20 minutes |
| Cultivate damping fluid | 0.1M sodium phosphate, pH7.4 |
| Quantization method | The spectrophotometric quantifying of thiocholine |
| The significance standard | Maximal stimulation effect or restraining effect 〉=50% |
Described detected result is summarized as follows:
Embodiment 7: observed value that body temperature reduces and the agent of determining to produce the cholinergic effect
Weight range and time cycle
The described method of delivering in European Journal ofPharmacology " European pharmacology magazine " 187:193-199 in nineteen ninety according to people such as Freedman of article, determine the induction phenomena of the body temperature reduction that compound of the present invention produces, the content of above-mentioned article is hereby incorporated by.Before testing, male BKTO mouse (20-30 gram) is positioned over respectively in the synthetic glass cage, and kept at least 60 minutes at ambient temperature.Carry out 1 minute constraint (restrain) in just mouse being positioned over Perspex restriction cage in 20 minutes, and utilizing thermometer to measure rectal temperature, described thermometer is for example Jenway 200 or Sensotek BAT-12.Use the circular probe of 2.5 millimeters of diameters that inserts rectum 2.4 centimeters or use the circular probe of 1.5 millimeters of diameters that inserts rectum 1.6 centimeters that the observed value of temperature is assessed.In above-mentioned two kinds of situations, all use liquid parafilm to seal film the probe that inserts is lubricated.Use the compound of the present invention of low dosage that mouse is handled.Use by endoperitoneal approach and to be tried material, the dosage range of using is generally the 0.0001-1.0 mg/kg.
Determine that according to following description compound of the present invention produces cholinergic required dosage range and the time cycle of effect.
Host: 208 of male CD IGS (being derived from Sprague Dawley) rats accepting 126-150 gram, in about 1 time-of-week before on-test, place four in each cage, carry out the illumination/dark cycle (light application time 6 point-18 points) of rule, and give food and water arbitrarily.
Device: use the 1 milliliter of tuberculin syringe that has 25-pin position (gauge), 5/8 inch syringe needle to finish injection.In the big mouse cage of polycarbonate of 10 inches of 5.5x, observe.Utilize the rat rectal prob of Model BAT-12 electronic clinical thermometer to read temperature.
The preparation of compound: test-compound for example is dissolved in 0.9% the physiological saline.Carry out five equilibrium and dilute the concentration for preparing than low dosage by solution higher concentration.If described test-compound has sufficient solvability, volume injected is 1 ml/kg.If solvability is relatively poor, maximum volume injected is 5 ml/kg.The path of using is subcutaneous.Sample plan is as follows:
Included treatment group (N=3, physiological saline are 6)
Physiological saline
1,3,10,30, and [(S)-Li Wasi bright] of 100 mg/kg
1,3,10,30, and (the R)-Li Wasi's of 100 mg/kg is bright
Test-compound
Test-compound is with 1,3,10,30, and the dosage of 100 mg/kg is used
Process: take described rat to the test room with cage.Before injecting, read datum temperature.Through after the subcutaneous injection, described rat is positioned in the observation cage.Through 0.5 hour after the injection, 1 hour, when 2 hours and 4 hours, the overall sign of brief observation; The salivation degree is divided, be divided into no salivation, significantly have salivation, perhaps salivation is a lot; And read rectal temperature.In the observation of overall sign, pay special attention to spontaneous shrink (muscle twitch), tremble/ataxia, and abnormal gait.(NB: described test has been designed to allow at each time point of per minute a rat to be estimated).Division and temperature to salivation under this restrained condition are determined, but are only noted the most outstanding overall sign.Through behind described 4 hours view-point, perhaps after observing painful sign, described rat is implemented euthanasia by sucking carbonic acid gas.
Data analysis: with the overall sign at each time point place, salivation is divided, and temperature is listed as into table and is used for testing.This be in a kind of host and the host between combination, the design in the described host is with comparing, and is designed for definite effective dose between described host.That is, the effect and the reading that is about to be read before the injection of the described compound that measures compared, and measure difference on the described compound dosage that exists between three groups of rats.Cause the possibility of strong effect in order to take precautions against appearance because of the replicate measurement rectal temperature, use a solvent group (N=6), be used to carry out the bright pilot of (s)-Li Wasi.
Body temperature reduction and dosimetric result are as follows
Equivalent
Although the present invention has carried out concrete expression and description with reference to preferred implementation wherein, those skilled in the art it will be understood that and can carry out various changes to it in form and on the details that this will not deviate from scope of the present invention.
Claims (32)
1. one kind according to the compound shown in formula I or the formula II:
Or the acceptable salt of the medicine of this compound, wherein
Q is selected from the structural formula shown in the table 1;
R
1Be selected from hydrogen, unsubstituted alkyl, substituted alkyl, unsubstituted aralkyl, substituted aralkyl, unsubstituted iso-alkyl, and substituted iso-alkyl or R
1It is dead key;
R
3, R
4And R
5Independently be selected from unsubstituted alkyl and hydrogen respectively separately.
2. compound according to claim 1, wherein said compound are the compounds shown in the formula I.
3. compound according to claim 1, wherein said compound are the compounds shown in the formula II.
4. according to any described compound, wherein a R among the claim 1-3
3, R
4And R
5In at least one be unsubstituted alkyl.
5. compound according to claim 4, wherein R
3, R
4And R
5In at least two be unsubstituted alkyl.
6. according to any described compound, wherein a R among the claim 1-5
1It is dead key.
7. according to any described compound, wherein a R among the claim 1-5
1Be selected from hydrogen, substituted and unsubstituted alkyl.
8. according to any described compound, wherein a R in claim 1-5 or 7
1Be selected from methyl, hydrogen, ethyl, butyl, sec.-propyl, propyl group, and the tertiary butyl.
9. according to any described compound, wherein a R in claim 1-5 or 7
1It is unsubstituted alkyl.
10. want 9 described compound, wherein R according to right
1It is branched-chain alkyl.
11. want 9 described compound, wherein R according to right
1It is methyl.
12. want 8 described compound, wherein R according to right
1Be hydrogen or methyl.
13. according to any described compound among the claim 1-12, wherein Q is selected from P, S, R, Z, Y, SS, JJJ, YY, EEE, UU, AA, FFF, CCC, U, T, X, V, P, Q ', U, BB, CC, DD, SSS, TTT, MM, UU, and XX.
14. according to any described compound among the claim 1-12, wherein Q is selected from X, V, P, Q ', U, R, S, Y, T, Z, AA, BB, CC, DD, SSS, TTT, MM, UU, and XX.
15. compound that is selected from the following compound: compound 2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30, and 31.
16. compound according to claim 1, wherein Q is selected from X, V, P, Q ', U, R, S, Y, T, Z, AA, BB, CC, DD, SSS, TTT, MM, UU, and XX.
17. a pharmaceutical composition, described pharmaceutical composition comprise any described compound among the claim 1-16, perhaps the acceptable salt of the medicine of this compound.
18. any described compound is used for application in the medicine that the illness relevant with the activity of acetylcholinesterase to individuality treat in preparation among the claim 1-17, wherein said compound can acetylcholine esterase inhibition.
19. any described compound is used for application in the medicine that the illness relevant with the activity of acetylcholinesterase to individuality treat in preparation among the claim 1-17, wherein said illness is selected from central nervous system disorders, peripheral nervous system illness and disorder of autonomic nervous system.
20. application according to claim 19, wherein said central nervous system disorders is selected from the group of being made up of following disease: Parkinson's disease, memory injury and cognitive function damage.
21. application according to claim 20, wherein said memory injury betides among the mankind, the described mankind suffer from the illness relevant with the activity of acetylcholinesterase, wherein said illness is selected from Alzheimer's disease, the lethe relevant with the age, memory is consolidated the damage of aspect, the damage of short-term memory, mild cognitive function damage and multiple sclerosis.
22. any described compound is used for increasing application in the medicine of vagusstoff of individuality in preparation among the claim 1-17, wherein said compound can suppress Pseudocholinesterase, thereby increases vagusstoff.
23. any described compound is used for the treatment of application in the medicine of individual cholinergic disappearance in preparation among the claim 1-17, wherein said compound can suppress Pseudocholinesterase, thereby treats the cholinergic disappearance of described individuality.
24. application according to claim 23, wherein said cholinergic disappearance is an Alzheimer's disease.
25. any described compound is used for the treatment of application in the medicine of individual memory injury in preparation among the claim 1-17, wherein said compound can suppress Pseudocholinesterase, thereby treats the memory injury of described individuality.
26. application according to claim 25, the memory injury of wherein said individuality is selected from the damage that memory is consolidated the aspect, the damage of long-term memory and the damage of short-term memory.
27. application according to claim 26, wherein said memory injury is relevant with the illness that is selected from following disease: Alzheimer's disease, the lethe relevant with the age, mild cognitive function damage and multiple sclerosis.
28. any described compound is used for application in the medicine that the illness relevant with the activity of acetylcholinesterase to individuality treat in preparation among the claim 1-17, wherein said illness is a kind of neurological conditions, is selected from delayed gastric emptying, note damaged many moving obstacles (ADHD), phobia, somnopathy, apoplexy, insane, pain, anticholinergic agents is excessive, tobacco relies on, Parkinson's disease, memory injury, and cognitive function damage.
29. any described compound is used for application in the medicine that the illness relevant with the activity of acetylcholinesterase to individuality treat in preparation among the claim 1-17, wherein said illness is selected from glaucoma, the tumour illness, delayed gastric emptying is noted damaged many moving obstacles (ADHD), phobia, apoplexy, multiple sclerosis, somnopathy, insane, pain, anticholinergic agents is excessive, and tobacco relies on, cardiovascular disorder, infectation of bacteria, Meniere's disease, virus infection, allergy, and spasticity.
30. any described compound is used for application in the medicine that the illness relevant with the activity of acetylcholinesterase to individuality treat in preparation among the claim 1-17, wherein said illness is selected from delayed gastric emptying, note damaged many moving obstacles (ADHD), phobia, somnopathy, apoplexy, insane, pain, anticholinergic agents is excessive, and tobacco relies on.
31. any described compound is used for application in the medicine that the illness relevant with the activity of acetylcholinesterase to individuality treat in preparation among the claim 1-17, wherein said illness is that anticholinergic agents is excessive.
32. according to any described application among the claim 18-31, wherein said individuality is human.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US89911107P | 2007-02-02 | 2007-02-02 | |
| US60/899,111 | 2007-02-02 | ||
| US60/959,901 | 2007-07-16 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101631770A true CN101631770A (en) | 2010-01-20 |
Family
ID=41576350
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN200880007756A Pending CN101631770A (en) | 2007-02-02 | 2008-02-04 | The compound that suppresses Pseudocholinesterase |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101631770A (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102464608A (en) * | 2010-11-15 | 2012-05-23 | 江苏先声药物研究有限公司 | Compound and application thereof as L-calcium channel retarder or/and acetylcholinesterase inhibitor |
| CN102603675A (en) * | 2012-02-06 | 2012-07-25 | 江苏先声药物研究有限公司 | Piperazine compound and application thereof |
| CN103826633A (en) * | 2011-07-28 | 2014-05-28 | 凯姆制药公司 | Methylphenidate prodrugs, methods for their preparation and use |
| CN106187898A (en) * | 2015-04-29 | 2016-12-07 | 中南大学 | Carbamate derivatives and preparation method and use thereof |
| CN106458866A (en) * | 2014-02-28 | 2017-02-22 | 爱思开生物制药株式会社 | Aminocarbonyl carbamate compound |
-
2008
- 2008-02-04 CN CN200880007756A patent/CN101631770A/en active Pending
Cited By (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102464608A (en) * | 2010-11-15 | 2012-05-23 | 江苏先声药物研究有限公司 | Compound and application thereof as L-calcium channel retarder or/and acetylcholinesterase inhibitor |
| WO2012065527A1 (en) * | 2010-11-15 | 2012-05-24 | 江苏先声药物研究有限公司 | Compouds and uses as l-type calcium channel blocker and/or acetylcholinesterase inhibitor thereof |
| CN102464608B (en) * | 2010-11-15 | 2016-05-11 | 江苏先声药物研究有限公司 | Compound and as L-type calcium channel blocker or/and the application of acetylcholinesteraseinhibitors inhibitors |
| CN103826633A (en) * | 2011-07-28 | 2014-05-28 | 凯姆制药公司 | Methylphenidate prodrugs, methods for their preparation and use |
| CN107261148A (en) * | 2011-07-28 | 2017-10-20 | 凯姆制药公司 | Methylphenidate prodrug, its preparation and application |
| CN107261148B (en) * | 2011-07-28 | 2021-07-13 | 凯姆制药公司 | Methylphenidate prodrugs, methods of making and using the same |
| CN102603675A (en) * | 2012-02-06 | 2012-07-25 | 江苏先声药物研究有限公司 | Piperazine compound and application thereof |
| CN102603675B (en) * | 2012-02-06 | 2014-04-02 | 江苏先声药物研究有限公司 | Piperazine compound and application thereof |
| CN106458866A (en) * | 2014-02-28 | 2017-02-22 | 爱思开生物制药株式会社 | Aminocarbonyl carbamate compound |
| CN106458866B (en) * | 2014-02-28 | 2018-12-07 | 爱思开生物制药株式会社 | Aminocarbonyl carbamate compound |
| CN106187898A (en) * | 2015-04-29 | 2016-12-07 | 中南大学 | Carbamate derivatives and preparation method and use thereof |
| CN106187898B (en) * | 2015-04-29 | 2019-01-18 | 中南大学 | Carbamate derivatives and its preparation method and use |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US8101782B2 (en) | Compounds that inhibit cholinesterase | |
| JP4676961B2 (en) | Carbamoyl esters that inhibit cholinesterase and release pharmacologically active substances | |
| JP2010518010A5 (en) | ||
| EP2344447B1 (en) | Gaba conjugates and methods of use thereof | |
| KR20050088992A (en) | Modulation of anxiety through blockade of anandamide hydrolysis | |
| CN101631770A (en) | The compound that suppresses Pseudocholinesterase | |
| US20240277665A1 (en) | Asymmetric allyl tryptamines | |
| CA2440834A1 (en) | Anti-epileptogenic agents | |
| US20250179042A1 (en) | Use of deuterated empathogens as therapeutic agents | |
| US20250049736A1 (en) | Sulfonamide derivatives and their use as soluble epoxide hydrolase inhibitors | |
| HK1138565A (en) | Compounds that inhibit cholinesterase | |
| US12180176B2 (en) | Fluorinated empathogens | |
| US20110251175A1 (en) | Stigmine Conjugates for Substance Use Disorders | |
| MXPA06004449A (en) | Carbamoyl esters that inhibit cholinesterase and release pharmacologically active agents |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| REG | Reference to a national code |
Ref country code: HK Ref legal event code: DE Ref document number: 1138565 Country of ref document: HK |
|
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20100120 |
|
| REG | Reference to a national code |
Ref country code: HK Ref legal event code: WD Ref document number: 1138565 Country of ref document: HK |