ZA200400525B - Isoxazolopyridinones and use thereof in the treatment of parkinson's disease. - Google Patents

Isoxazolopyridinones and use thereof in the treatment of parkinson's disease. Download PDF

Info

Publication number: ZA200400525B
Authority: ZA; South Africa
Prior art keywords: compound; phenyl; hydroxy; methyl; free base
Prior art date: 2001-08-15

Application number

ZA200400525A

Other languages

English (en)

Inventor

Samuel Hintermann

Bastian Hengerer

Ulrike Von Krosigk

Original Assignee

Novartis Ag

Priority date (The priority date 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 date listed.)

2001-08-15

Filing date

2004-01-23

Publication date

2005-04-01

2004-01-23 Application filed by Novartis Ag filed Critical Novartis Ag

2005-04-01 Publication of ZA200400525B publication Critical patent/ZA200400525B/en

Links

208000018737 Parkinson disease Diseases 0.000 title claims description 13
WJLKGZPFGUBCPD-UHFFFAOYSA-N 1h-[1,2]oxazolo[4,3-b]pyridin-3-one Chemical class C1=CN=C2C(=O)ONC2=C1 WJLKGZPFGUBCPD-UHFFFAOYSA-N 0.000 title description 3
150000001875 compounds Chemical class 0.000 claims description 75
150000003839 salts Chemical group 0.000 claims description 22
239000001257 hydrogen Substances 0.000 claims description 18
229910052739 hydrogen Inorganic materials 0.000 claims description 18
238000000034 method Methods 0.000 claims description 18
239000002253 acid Substances 0.000 claims description 17
239000012458 free base Substances 0.000 claims description 16
-1 benzo[1 ,2,5]oxadiazol-5-yl Chemical group 0.000 claims description 13
229910052736 halogen Inorganic materials 0.000 claims description 11
150000002367 halogens Chemical class 0.000 claims description 11
239000000460 chlorine Substances 0.000 claims description 8
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
125000000217 alkyl group Chemical group 0.000 claims description 7
125000001064 morpholinomethyl group Chemical group [H]C([H])(*)N1C([H])([H])C([H])([H])OC([H])([H])C1([H])[H] 0.000 claims description 5
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
239000003814 drug Substances 0.000 claims description 4
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
239000008194 pharmaceutical composition Substances 0.000 claims description 4
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
KPXIVOYDTAKEBC-UHFFFAOYSA-N 6-[4-[(dimethylamino)methyl]phenyl]-3-phenyl-5H-[1,2]oxazolo[4,5-c]pyridin-4-one Chemical compound C1=CC(CN(C)C)=CC=C1C(NC1=O)=CC2=C1C(C=1C=CC=CC=1)=NO2 KPXIVOYDTAKEBC-UHFFFAOYSA-N 0.000 claims description 3
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 3
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 3
239000008186 active pharmaceutical agent Substances 0.000 claims description 3
125000005605 benzo group Chemical group 0.000 claims description 3
229910052801 chlorine Inorganic materials 0.000 claims description 3
239000003937 drug carrier Substances 0.000 claims description 3
229940088679 drug related substance Drugs 0.000 claims description 3
229910052731 fluorine Inorganic materials 0.000 claims description 3
239000011737 fluorine Substances 0.000 claims description 3
238000004519 manufacturing process Methods 0.000 claims description 3
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
238000002360 preparation method Methods 0.000 claims description 3
YCAACZFPADQMAR-UHFFFAOYSA-N 6-[4-(2-methoxyethoxymethyl)phenyl]-5-methyl-3-phenyl-[1,2]oxazolo[4,5-c]pyridin-4-one Chemical compound C1=CC(COCCOC)=CC=C1C(N(C1=O)C)=CC2=C1C(C=1C=CC=CC=1)=NO2 YCAACZFPADQMAR-UHFFFAOYSA-N 0.000 claims description 2
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 2
125000006222 dimethylaminomethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])* 0.000 claims description 2
125000006533 methyl amino methyl group Chemical group [H]N(C([H])([H])[H])C([H])([H])* 0.000 claims description 2
239000008024 pharmaceutical diluent Substances 0.000 claims description 2
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 2
150000002431 hydrogen Chemical group 0.000 claims 9
125000003282 alkyl amino group Chemical group 0.000 claims 1
238000001819 mass spectrum Methods 0.000 description 39
239000007787 solid Substances 0.000 description 34
239000000243 solution Substances 0.000 description 26
239000003795 chemical substances by application Substances 0.000 description 19
JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Substances N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 15
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 15
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
101150026563 NR4A2 gene Proteins 0.000 description 11
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
239000000725 suspension Substances 0.000 description 10
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
125000004435 hydrogen atom Chemical class [H]* 0.000 description 9
239000000203 mixture Substances 0.000 description 9
VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 8
150000002825 nitriles Chemical class 0.000 description 8
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
238000000746 purification Methods 0.000 description 6
239000002904 solvent Substances 0.000 description 6
241001465754 Metazoa Species 0.000 description 5
238000006243 chemical reaction Methods 0.000 description 5
DCKOQOHEZADEJX-UHFFFAOYSA-N n,5-dimethyl-3-phenyl-1,2-oxazole-4-carboxamide Chemical compound CNC(=O)C1=C(C)ON=C1C1=CC=CC=C1 DCKOQOHEZADEJX-UHFFFAOYSA-N 0.000 description 5
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
LWRSYTXEQUUTKW-UHFFFAOYSA-N 2,4-dimethoxybenzaldehyde Chemical compound COC1=CC=C(C=O)C(OC)=C1 LWRSYTXEQUUTKW-UHFFFAOYSA-N 0.000 description 4
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 4
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 4
108700008625 Reporter Genes Proteins 0.000 description 4
238000003556 assay Methods 0.000 description 4
229960003638 dopamine Drugs 0.000 description 4
230000000694 effects Effects 0.000 description 4
238000000338 in vitro Methods 0.000 description 4
210000001259 mesencephalon Anatomy 0.000 description 4
239000012074 organic phase Substances 0.000 description 4
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
238000010792 warming Methods 0.000 description 4
WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 3
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
CABBIZSFTLIHJT-UHFFFAOYSA-N 5-methyl-3,6-diphenyl-[1,2]oxazolo[4,3-c]pyridin-4-one Chemical compound C=12C(=O)N(C)C(C=3C=CC=CC=3)=CC2=NOC=1C1=CC=CC=C1 CABBIZSFTLIHJT-UHFFFAOYSA-N 0.000 description 3
WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
PKRWWZCDLJSJIF-UHFFFAOYSA-N Piperonylonitrile Chemical compound N#CC1=CC=C2OCOC2=C1 PKRWWZCDLJSJIF-UHFFFAOYSA-N 0.000 description 3
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
239000012267 brine Substances 0.000 description 3
239000006260 foam Substances 0.000 description 3
238000001727 in vivo Methods 0.000 description 3
108020001756 ligand binding domains Proteins 0.000 description 3
239000012071 phase Substances 0.000 description 3
238000010992 reflux Methods 0.000 description 3
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
238000001228 spectrum Methods 0.000 description 3
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
QCSOEUMGZOKXPJ-UHFFFAOYSA-N 4-[(dimethylamino)methyl]benzonitrile Chemical compound CN(C)CC1=CC=C(C#N)C=C1 QCSOEUMGZOKXPJ-UHFFFAOYSA-N 0.000 description 2
GCNTZFIIOFTKIY-UHFFFAOYSA-N 4-hydroxypyridine Chemical compound OC1=CC=NC=C1 GCNTZFIIOFTKIY-UHFFFAOYSA-N 0.000 description 2
RIBDJXAYIQCEGU-UHFFFAOYSA-N 6-(2,4-dimethoxyphenyl)-5-methyl-3-phenyl-[1,2]oxazolo[4,5-c]pyridin-4-one Chemical compound COC1=CC(OC)=CC=C1C(N(C1=O)C)=CC2=C1C(C=1C=CC=CC=1)=NO2 RIBDJXAYIQCEGU-UHFFFAOYSA-N 0.000 description 2
PPUUWHCQKUSMQV-UHFFFAOYSA-N 6-[4-(2-hydroxyethoxymethyl)phenyl]-5-methyl-3-phenyl-[1,2]oxazolo[4,5-c]pyridin-4-one Chemical compound C1=2C(=O)N(C)C(C=3C=CC(COCCO)=CC=3)=CC=2ON=C1C1=CC=CC=C1 PPUUWHCQKUSMQV-UHFFFAOYSA-N 0.000 description 2
VNIVDRLSISWMPB-UHFFFAOYSA-N 6-[4-(bromomethyl)phenyl]-5-methyl-3-phenyl-[1,2]oxazolo[4,5-c]pyridin-4-one Chemical compound C1=2C(=O)N(C)C(C=3C=CC(CBr)=CC=3)=CC=2ON=C1C1=CC=CC=C1 VNIVDRLSISWMPB-UHFFFAOYSA-N 0.000 description 2
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
241000124008 Mammalia Species 0.000 description 2
FEIOASZZURHTHB-UHFFFAOYSA-N Methyl-p-formylbenzoate Natural products COC(=O)C1=CC=C(C=O)C=C1 FEIOASZZURHTHB-UHFFFAOYSA-N 0.000 description 2
125000003545 alkoxy group Chemical group 0.000 description 2
150000001408 amides Chemical class 0.000 description 2
229910052786 argon Inorganic materials 0.000 description 2
239000002585 base Substances 0.000 description 2
FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 2
238000000423 cell based assay Methods 0.000 description 2
238000011097 chromatography purification Methods 0.000 description 2
KVFDZFBHBWTVID-UHFFFAOYSA-N cyclohexanecarbaldehyde Chemical compound O=CC1CCCCC1 KVFDZFBHBWTVID-UHFFFAOYSA-N 0.000 description 2
210000005064 dopaminergic neuron Anatomy 0.000 description 2
238000003818 flash chromatography Methods 0.000 description 2
125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 2
229910052744 lithium Inorganic materials 0.000 description 2
DQNUZURLZCIRLZ-UHFFFAOYSA-N n,3-dimethyl-5-phenyl-1,2-oxazole-4-carboxamide Chemical compound CC1=NOC(C=2C=CC=CC=2)=C1C(=O)NC DQNUZURLZCIRLZ-UHFFFAOYSA-N 0.000 description 2
SATCULPHIDQDRE-UHFFFAOYSA-N piperonal Chemical compound O=CC1=CC=C2OCOC2=C1 SATCULPHIDQDRE-UHFFFAOYSA-N 0.000 description 2
239000007858 starting material Substances 0.000 description 2
210000003523 substantia nigra Anatomy 0.000 description 2
AZUYLZMQTIKGSC-UHFFFAOYSA-N 1-[6-[4-(5-chloro-6-methyl-1H-indazol-4-yl)-5-methyl-3-(1-methylindazol-5-yl)pyrazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]prop-2-en-1-one Chemical compound ClC=1C(=C2C=NNC2=CC=1C)C=1C(=NN(C=1C)C1CC2(CN(C2)C(C=C)=O)C1)C=1C=C2C=NN(C2=CC=1)C AZUYLZMQTIKGSC-UHFFFAOYSA-N 0.000 description 1
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UELJMYRIGJUYLR-UHFFFAOYSA-N 3,6-diphenyl-5-propyl-[1,2]oxazolo[4,5-c]pyridin-4-one Chemical compound C1=2C(=O)N(CCC)C(C=3C=CC=CC=3)=CC=2ON=C1C1=CC=CC=C1 UELJMYRIGJUYLR-UHFFFAOYSA-N 0.000 description 1
WPXCVBULBNOMKR-UHFFFAOYSA-N 3-(2-chlorophenyl)-n,5-dimethyl-1,2-oxazole-4-carboxamide Chemical compound CNC(=O)C1=C(C)ON=C1C1=CC=CC=C1Cl WPXCVBULBNOMKR-UHFFFAOYSA-N 0.000 description 1
KLXSUMLEPNAZFK-UHFFFAOYSA-N 3-methoxybenzonitrile Chemical compound COC1=CC=CC(C#N)=C1 KLXSUMLEPNAZFK-UHFFFAOYSA-N 0.000 description 1
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KMLGFOAKCYHXCQ-UHFFFAOYSA-N 4-(diethylamino)benzonitrile Chemical compound CCN(CC)C1=CC=C(C#N)C=C1 KMLGFOAKCYHXCQ-UHFFFAOYSA-N 0.000 description 1
GJNGXPDXRVXSEH-UHFFFAOYSA-N 4-chlorobenzonitrile Chemical compound ClC1=CC=C(C#N)C=C1 GJNGXPDXRVXSEH-UHFFFAOYSA-N 0.000 description 1
VCZNNAKNUVJVGX-UHFFFAOYSA-N 4-methylbenzonitrile Chemical compound CC1=CC=C(C#N)C=C1 VCZNNAKNUVJVGX-UHFFFAOYSA-N 0.000 description 1
UYHCIOZMFCLUDP-UHFFFAOYSA-N 4-phenoxybenzonitrile Chemical compound C1=CC(C#N)=CC=C1OC1=CC=CC=C1 UYHCIOZMFCLUDP-UHFFFAOYSA-N 0.000 description 1
BPMBNLJJRKCCRT-UHFFFAOYSA-N 4-phenylbenzonitrile Chemical compound C1=CC(C#N)=CC=C1C1=CC=CC=C1 BPMBNLJJRKCCRT-UHFFFAOYSA-N 0.000 description 1
BTYZVJMWTDCGTR-UHFFFAOYSA-N 5,6-dimethyl-3-phenyl-[1,2]oxazolo[4,5-c]pyridin-4-one Chemical compound C1=2C(=O)N(C)C(C)=CC=2ON=C1C1=CC=CC=C1 BTYZVJMWTDCGTR-UHFFFAOYSA-N 0.000 description 1
ZBRIOJKIBZMZIZ-UHFFFAOYSA-N 5-cyclopropyl-3,6-diphenyl-[1,2]oxazolo[4,5-c]pyridin-4-one Chemical compound C=1C=CC=CC=1C1=CC=2ON=C(C=3C=CC=CC=3)C=2C(=O)N1C1CC1 ZBRIOJKIBZMZIZ-UHFFFAOYSA-N 0.000 description 1
QYWITVPSJGSOSW-UHFFFAOYSA-N 5-ethyl-6-(3-methoxyphenyl)-3-phenyl-[1,2]oxazolo[4,5-c]pyridin-4-one Chemical compound C1=2C(=O)N(CC)C(C=3C=C(OC)C=CC=3)=CC=2ON=C1C1=CC=CC=C1 QYWITVPSJGSOSW-UHFFFAOYSA-N 0.000 description 1
PENHKTNQUJMHIR-UHFFFAOYSA-N 5-methyl-3-phenyl-1,2-oxazole-4-carboxylic acid Chemical compound OC(=O)C1=C(C)ON=C1C1=CC=CC=C1 PENHKTNQUJMHIR-UHFFFAOYSA-N 0.000 description 1
QKGMJCLWMCCRRB-UHFFFAOYSA-N 5-methyl-3-phenyl-6-[4-(phenylmethoxymethyl)phenyl]-[1,2]oxazolo[4,5-c]pyridin-4-one Chemical compound C1=2C(=O)N(C)C(C=3C=CC(COCC=4C=CC=CC=4)=CC=3)=CC=2ON=C1C1=CC=CC=C1 QKGMJCLWMCCRRB-UHFFFAOYSA-N 0.000 description 1
IBQKWQHKJWZQRA-UHFFFAOYSA-N 5-methyl-3-phenyl-6-[4-(pyrrol-1-ylmethyl)phenyl]-[1,2]oxazolo[4,5-c]pyridin-4-one Chemical compound C1=2C(=O)N(C)C(C=3C=CC(CN4C=CC=C4)=CC=3)=CC=2ON=C1C1=CC=CC=C1 IBQKWQHKJWZQRA-UHFFFAOYSA-N 0.000 description 1
LJFFXXBCMTXSHN-UHFFFAOYSA-N 5-methyl-3-phenyl-6-pyridin-4-yl-[1,2]oxazolo[4,5-c]pyridin-4-one Chemical compound C1=2C(=O)N(C)C(C=3C=CN=CC=3)=CC=2ON=C1C1=CC=CC=C1 LJFFXXBCMTXSHN-UHFFFAOYSA-N 0.000 description 1
KNWAMIVNVXVFIO-UHFFFAOYSA-N 5-methyl-3-phenyl-n-propyl-1,2-oxazole-4-carboxamide Chemical compound CCCNC(=O)C1=C(C)ON=C1C1=CC=CC=C1 KNWAMIVNVXVFIO-UHFFFAOYSA-N 0.000 description 1
BESWQYUOFDGBAT-UHFFFAOYSA-N 5-methyl-6-(4-methylphenyl)-3-phenyl-[1,2]oxazolo[4,5-c]pyridin-4-one Chemical compound C1=CC(C)=CC=C1C(N(C1=O)C)=CC2=C1C(C=1C=CC=CC=1)=NO2 BESWQYUOFDGBAT-UHFFFAOYSA-N 0.000 description 1
KQVFNVQDUTYNCI-UHFFFAOYSA-N 5-methyl-6-(4-phenoxyphenyl)-3-phenyl-[1,2]oxazolo[4,5-c]pyridin-4-one Chemical compound C1=2C(=O)N(C)C(C=3C=CC(OC=4C=CC=CC=4)=CC=3)=CC=2ON=C1C1=CC=CC=C1 KQVFNVQDUTYNCI-UHFFFAOYSA-N 0.000 description 1
OPIIMVDOIZEYOE-UHFFFAOYSA-N 6-(1,3-benzodioxol-5-yl)-5-cyclopropyl-3-phenyl-[1,2]oxazolo[4,5-c]pyridin-4-one Chemical compound C=1C=C2OCOC2=CC=1C1=CC=2ON=C(C=3C=CC=CC=3)C=2C(=O)N1C1CC1 OPIIMVDOIZEYOE-UHFFFAOYSA-N 0.000 description 1
ULIDMONIXZNCET-UHFFFAOYSA-N 6-(1,3-benzodioxol-5-yl)-5-ethyl-3-phenyl-[1,2]oxazolo[4,5-c]pyridin-4-one Chemical compound C1=2C(=O)N(CC)C(C=3C=C4OCOC4=CC=3)=CC=2ON=C1C1=CC=CC=C1 ULIDMONIXZNCET-UHFFFAOYSA-N 0.000 description 1
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BBPFMYPJIKCJKZ-UHFFFAOYSA-N 6-(3,4-dimethoxyphenyl)-5-methyl-3-phenyl-[1,2]oxazolo[4,5-c]pyridin-4-one Chemical compound C1=C(OC)C(OC)=CC=C1C(N(C1=O)C)=CC2=C1C(C=1C=CC=CC=1)=NO2 BBPFMYPJIKCJKZ-UHFFFAOYSA-N 0.000 description 1
JAERTDMSEBWFIF-UHFFFAOYSA-N 6-(3,5-dimethoxyphenyl)-5-methyl-3-phenyl-[1,2]oxazolo[4,5-c]pyridin-4-one Chemical compound COC1=CC(OC)=CC(C=2N(C(=O)C=3C(C=4C=CC=CC=4)=NOC=3C=2)C)=C1 JAERTDMSEBWFIF-UHFFFAOYSA-N 0.000 description 1
KCZHOYHCNBXGMF-UHFFFAOYSA-N 6-(4-chlorophenyl)-5-methyl-3-phenyl-[1,2]oxazolo[4,3-c]pyridin-4-one Chemical compound C=12C(=O)N(C)C(C=3C=CC(Cl)=CC=3)=CC2=NOC=1C1=CC=CC=C1 KCZHOYHCNBXGMF-UHFFFAOYSA-N 0.000 description 1
QIPODYCQCKHDDA-UHFFFAOYSA-N 6-[4-[(dimethylamino)methyl]phenyl]-3-phenyl-5H-[1,2]oxazolo[4,3-c]pyridin-4-one Chemical compound C1=CC(CN(C)C)=CC=C1C1=CC2=NOC(C=3C=CC=CC=3)=C2C(=O)N1 QIPODYCQCKHDDA-UHFFFAOYSA-N 0.000 description 1
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239000005557 antagonist Substances 0.000 description 1
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239000007864 aqueous solution Substances 0.000 description 1
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230000004071 biological effect Effects 0.000 description 1
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230000037396 body weight Effects 0.000 description 1
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238000005893 bromination reaction Methods 0.000 description 1
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238000005570 heteronuclear single quantum coherence Methods 0.000 description 1
230000006698 induction Effects 0.000 description 1
239000003112 inhibitor Substances 0.000 description 1
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DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 1
JTUQHTUQSMTHHC-UHFFFAOYSA-N methyl 4-(5-methyl-4-oxo-3-phenyl-[1,2]oxazolo[4,3-c]pyridin-6-yl)benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1C1=CC2=NOC(C=3C=CC=CC=3)=C2C(=O)N1C JTUQHTUQSMTHHC-UHFFFAOYSA-N 0.000 description 1
MGJXBDMLVWIYOQ-UHFFFAOYSA-N methylazanide Chemical compound [NH-]C MGJXBDMLVWIYOQ-UHFFFAOYSA-N 0.000 description 1
239000004530 micro-emulsion Substances 0.000 description 1
239000000178 monomer Substances 0.000 description 1
125000006518 morpholino carbonyl group Chemical group [H]C1([H])OC([H])([H])C([H])([H])N(C(*)=O)C1([H])[H] 0.000 description 1
230000009427 motor defect Effects 0.000 description 1
HCUIEGLRDNPODU-UHFFFAOYSA-N n-cyclopropyl-5-methyl-3-phenyl-1,2-oxazole-4-carboxamide Chemical compound CC=1ON=C(C=2C=CC=CC=2)C=1C(=O)NC1CC1 HCUIEGLRDNPODU-UHFFFAOYSA-N 0.000 description 1
WUZODTCWKPXULS-UHFFFAOYSA-N n-ethyl-5-methyl-3-phenyl-1,2-oxazole-4-carboxamide Chemical compound CCNC(=O)C1=C(C)ON=C1C1=CC=CC=C1 WUZODTCWKPXULS-UHFFFAOYSA-N 0.000 description 1
MFDUBANTKQQBFU-UHFFFAOYSA-N n-methoxy-4-(2-methoxyethoxymethyl)-n-methylbenzamide Chemical compound COCCOCC1=CC=C(C(=O)N(C)OC)C=C1 MFDUBANTKQQBFU-UHFFFAOYSA-N 0.000 description 1
NCCHARWOCKOHIH-UHFFFAOYSA-N n-methylbenzamide Chemical compound CNC(=O)C1=CC=CC=C1 NCCHARWOCKOHIH-UHFFFAOYSA-N 0.000 description 1
230000004770 neurodegeneration Effects 0.000 description 1
108020004017 nuclear receptors Proteins 0.000 description 1
102000006255 nuclear receptors Human genes 0.000 description 1
108091008686 nuclear receptors type II Proteins 0.000 description 1
102000027507 nuclear receptors type II Human genes 0.000 description 1
239000012038 nucleophile Substances 0.000 description 1
238000010534 nucleophilic substitution reaction Methods 0.000 description 1
QVYRGXJJSLMXQH-UHFFFAOYSA-N orphenadrine Chemical compound C=1C=CC=C(C)C=1C(OCCN(C)C)C1=CC=CC=C1 QVYRGXJJSLMXQH-UHFFFAOYSA-N 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
239000008177 pharmaceutical agent Substances 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
230000023603 positive regulation of transcription initiation, DNA-dependent Effects 0.000 description 1
239000000843 powder Substances 0.000 description 1
229960003089 pramipexole Drugs 0.000 description 1
FASDKYOPVNHBLU-ZETCQYMHSA-N pramipexole Chemical compound C1[C@@H](NCCC)CCC2=C1SC(N)=N2 FASDKYOPVNHBLU-ZETCQYMHSA-N 0.000 description 1
239000002243 precursor Substances 0.000 description 1
230000001737 promoting effect Effects 0.000 description 1
108090000623 proteins and genes Proteins 0.000 description 1
102000004169 proteins and genes Human genes 0.000 description 1
GPHQHTOMRSGBNZ-UHFFFAOYSA-N pyridine-4-carbonitrile Chemical compound N#CC1=CC=NC=C1 GPHQHTOMRSGBNZ-UHFFFAOYSA-N 0.000 description 1
239000011541 reaction mixture Substances 0.000 description 1
108020003175 receptors Proteins 0.000 description 1
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229960003946 selegiline Drugs 0.000 description 1
MEZLKOACVSPNER-GFCCVEGCSA-N selegiline Chemical compound C#CCN(C)[C@H](C)CC1=CC=CC=C1 MEZLKOACVSPNER-GFCCVEGCSA-N 0.000 description 1
239000000741 silica gel Substances 0.000 description 1
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239000007962 solid dispersion Substances 0.000 description 1
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239000000126 substance Substances 0.000 description 1
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208000024891 symptom Diseases 0.000 description 1
238000004448 titration Methods 0.000 description 1
229960004603 tolcapone Drugs 0.000 description 1
MIQPIUSUKVNLNT-UHFFFAOYSA-N tolcapone Chemical compound C1=CC(C)=CC=C1C(=O)C1=CC(O)=C(O)C([N+]([O-])=O)=C1 MIQPIUSUKVNLNT-UHFFFAOYSA-N 0.000 description 1
238000013518 transcription Methods 0.000 description 1
230000035897 transcription Effects 0.000 description 1

Classifications

- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/437—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/04—Ortho-condensed systems
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
General Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
Medicinal Chemistry (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Biomedical Technology (AREA)
Neurology (AREA)
Neurosurgery (AREA)
Psychology (AREA)
Epidemiology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Plural Heterocyclic Compounds (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)

ZA200400525A 2001-08-15 2004-01-23 Isoxazolopyridinones and use thereof in the treatment of parkinson's disease. ZA200400525B (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
GBGB0119911.6A GB0119911D0 (en)	2001-08-15	2001-08-15	Organic Compounds

Publications (1)

Publication Number	Publication Date
ZA200400525B true ZA200400525B (en)	2005-04-01

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ID=9920454

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
ZA200400525A ZA200400525B (en)	2001-08-15	2004-01-23	Isoxazolopyridinones and use thereof in the treatment of parkinson's disease.

Country Status (24)

Country	Link
US (1)	US7087756B2 (es)
EP (1)	EP1418912B1 (es)
JP (1)	JP2005501847A (es)
KR (1)	KR20040029429A (es)
CN (1)	CN100384418C (es)
AR (1)	AR036351A1 (es)
AT (1)	ATE355059T1 (es)
BR (1)	BR0211903A (es)
CA (1)	CA2454762A1 (es)
CO (1)	CO5560566A2 (es)
DE (1)	DE60218484T2 (es)
EC (1)	ECSP044971A (es)
ES (1)	ES2282467T3 (es)
GB (1)	GB0119911D0 (es)
HU (1)	HUP0401325A3 (es)
IL (1)	IL160018A0 (es)
MX (1)	MXPA04001419A (es)
NO (1)	NO20040659L (es)
PE (1)	PE20030356A1 (es)
PL (1)	PL366848A1 (es)
PT (1)	PT1418912E (es)
RU (1)	RU2004107847A (es)
WO (1)	WO2003015780A2 (es)
ZA (1)	ZA200400525B (es)

Families Citing this family (13)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CA2451057A1 (en) *	2001-06-14	2002-12-27	Banyu Pharmaceutical Co., Ltd.	Novel isoxazolopyridone derivatives and use thereof
CN1984894A (zh) *	2004-05-14	2007-06-20	Irm责任有限公司	作为ppar调节剂的化合物和组合物
WO2007098047A2 (en) *	2006-02-16	2007-08-30	The Mclean Hospital Corporation	Methods and compositions for the treatment of parkinson's disease
AU2007275301A1 (en)	2006-07-20	2008-01-24	Amgen Inc.	Substituted azole aromatic heterocycles as inhibitors of 11-beta-HSD-1
FR2906250B1 (fr) *	2006-09-22	2008-10-31	Sanofi Aventis Sa	Derives de 2-aryl-6phenyl-imidazo(1,2-a) pyridines, leur preparation et leur application en therapeutique
FR2933609B1 (fr) *	2008-07-10	2010-08-27	Fournier Lab Sa	Utilisation de derives d'indole comme activateurs de nurr-1, pour le traitement de la maladie de parkinson.
CA2749585A1 (en)	2009-01-13	2010-07-22	Van Andel Research Institute	Methods of using substituted isoxazolo pyridinones as dissociated glucocorticoids
FR2950053B1 (fr)	2009-09-11	2014-08-01	Fournier Lab Sa	Utilisation de derives d'indole benzoique comme activateurs de nurr-1, pour le traitement de la maladie de parkinson
FR2955110A1 (fr)	2010-01-08	2011-07-15	Fournier Lab Sa	Nouveaux derives de type pyrrolopyridine benzoique
DE102011085038A1 (de)	2011-10-21	2013-04-25	Tesa Se	Verfahren zur Kapselung einer elektronischen Anordnung
CN105744937A (zh)	2013-09-25	2016-07-06	范安德尔研究所	高效糖皮质激素
KR20170033630A (ko)	2015-09-17	2017-03-27	(주)다올	도로용 경계블럭
RU2019111101A (ru)	2016-10-14	2020-11-16	Ван Андель Рисерч Инститьют	Структуры и механизм для дизайна высокоактивных глюкокортикоидов

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Publication number	Priority date	Publication date	Assignee	Title
SE7602542L (sv) *	1975-03-14	1976-09-15	Sandoz Ag	3-(alfa-iminobensyl)-4-hydroxi-2(lh)-pyridoner
US4064251A (en) *	1976-06-25	1977-12-20	Sandoz, Inc.	Substituted hydroxy pyridones
US4049813A (en) *	1976-07-15	1977-09-20	Sandoz, Inc.	Substituted isoxazolo pyridinones
US4238616A (en)	1977-01-19	1980-12-09	Sandoz, Inc.	3-(Substituted)phenyl-5-(β-hydroxyphenethyl)-N-(alkyl)-isoxazole-4-carboxamides
DE2801190A1 (de) *	1977-01-19	1978-07-20	Sandoz Ag	3-(alpha-iminobenzyl)-4-hydroxy-2(1h)- pyridon-derivat
US4113727A (en) *	1977-04-26	1978-09-12	Sandoz, Inc.	Process for the preparation of substituted isoxazolo[4,5-c]pyridin-4-(5H)-ones
CA2451057A1 (en) *	2001-06-14	2002-12-27	Banyu Pharmaceutical Co., Ltd.	Novel isoxazolopyridone derivatives and use thereof

2001
- 2001-08-15 GB GBGB0119911.6A patent/GB0119911D0/en not_active Ceased
2002
- 2002-08-13 AR ARP020103046A patent/AR036351A1/es unknown
- 2002-08-14 IL IL16001802A patent/IL160018A0/xx unknown
- 2002-08-14 CN CNB028159268A patent/CN100384418C/zh not_active Expired - Fee Related
- 2002-08-14 EP EP02772157A patent/EP1418912B1/en not_active Expired - Lifetime
- 2002-08-14 PT PT02772157T patent/PT1418912E/pt unknown
- 2002-08-14 MX MXPA04001419A patent/MXPA04001419A/es unknown
- 2002-08-14 AT AT02772157T patent/ATE355059T1/de not_active IP Right Cessation
- 2002-08-14 US US10/486,569 patent/US7087756B2/en not_active Expired - Fee Related
- 2002-08-14 CA CA002454762A patent/CA2454762A1/en not_active Abandoned
- 2002-08-14 PE PE2002000734A patent/PE20030356A1/es not_active Application Discontinuation
- 2002-08-14 PL PL02366848A patent/PL366848A1/xx not_active Application Discontinuation
- 2002-08-14 RU RU2004107847/15A patent/RU2004107847A/ru not_active Application Discontinuation
- 2002-08-14 DE DE60218484T patent/DE60218484T2/de not_active Expired - Lifetime
- 2002-08-14 WO PCT/EP2002/009134 patent/WO2003015780A2/en active IP Right Grant
- 2002-08-14 ES ES02772157T patent/ES2282467T3/es not_active Expired - Lifetime
- 2002-08-14 BR BR0211903-0A patent/BR0211903A/pt not_active IP Right Cessation
- 2002-08-14 JP JP2003520739A patent/JP2005501847A/ja not_active Withdrawn
- 2002-08-14 KR KR10-2004-7002124A patent/KR20040029429A/ko not_active Ceased
- 2002-08-14 HU HU0401325A patent/HUP0401325A3/hu unknown
2004
- 2004-01-23 ZA ZA200400525A patent/ZA200400525B/en unknown
- 2004-02-03 EC EC2004004971A patent/ECSP044971A/es unknown
- 2004-02-13 NO NO20040659A patent/NO20040659L/no not_active Application Discontinuation
- 2004-03-12 CO CO04023011A patent/CO5560566A2/es not_active Application Discontinuation

Also Published As

Publication number	Publication date
HUP0401325A2 (hu)	2004-10-28
GB0119911D0 (en)	2001-10-10
EP1418912B1 (en)	2007-02-28
ECSP044971A (es)	2004-03-23
AR036351A1 (es)	2004-09-01
CN1635889A (zh)	2005-07-06
PE20030356A1 (es)	2003-05-14
CA2454762A1 (en)	2003-02-27
WO2003015780A2 (en)	2003-02-27
PL366848A1 (en)	2005-02-07
ATE355059T1 (de)	2006-03-15
WO2003015780A8 (en)	2004-05-21
BR0211903A (pt)	2004-09-21
HUP0401325A3 (en)	2005-09-28
US20040248893A1 (en)	2004-12-09
JP2005501847A (ja)	2005-01-20
DE60218484D1 (de)	2007-04-12
RU2004107847A (ru)	2005-05-10
IL160018A0 (en)	2004-06-20
ES2282467T3 (es)	2007-10-16
CO5560566A2 (es)	2005-09-30
US7087756B2 (en)	2006-08-08
NO20040659D0 (no)	2004-02-13
MXPA04001419A (es)	2004-05-27
CN100384418C (zh)	2008-04-30
WO2003015780A3 (en)	2003-11-13
KR20040029429A (ko)	2004-04-06
EP1418912A2 (en)	2004-05-19
NO20040659L (no)	2004-02-13
PT1418912E (pt)	2007-05-31
DE60218484T2 (de)	2007-11-15

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