HRP960277A2 - Novel compounds, the preparation and use thereof - Google Patents

Novel compounds, the preparation and use thereof Download PDF

Info

Publication number: HRP960277A2
Authority: HR; Croatia
Prior art keywords: methyl; acid; tert; tumor; carbonyl
Prior art date: 1995-06-07

Application number

HR08/472,453A

Other languages

English (en)

Croatian (hr)

Inventor

Andreas Haupt

Franz Emling

A Cynthia Romerdahl

Original Assignee

Basf 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.)

1995-06-07

Filing date

1996-06-06

Publication date

1997-10-31

1996-06-06 Application filed by Basf Ag filed Critical Basf Ag

1997-10-31 Publication of HRP960277A2 publication Critical patent/HRP960277A2/hr

Links

150000001875 compounds Chemical class 0.000 title claims description 32
238000002360 preparation method Methods 0.000 title description 3
-1 2-tert.butylglycyl Chemical group 0.000 claims description 52
108090000765 processed proteins & peptides Proteins 0.000 claims description 32
238000000034 method Methods 0.000 claims description 29
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 27
206010028980 Neoplasm Diseases 0.000 claims description 19
102000004196 processed proteins & peptides Human genes 0.000 claims description 14
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 8
125000000741 isoleucyl group Chemical group [H]N([H])C(C(C([H])([H])[H])C([H])([H])C([H])([H])[H])C(=O)O* 0.000 claims description 8
239000002253 acid Substances 0.000 claims description 6
241000124008 Mammalia Species 0.000 claims description 5
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 5
229950003188 isovaleryl diethylamide Drugs 0.000 claims description 5
125000002114 valyl group Chemical group 0.000 claims description 5
239000008194 pharmaceutical composition Substances 0.000 claims description 4
150000003839 salts Chemical class 0.000 claims description 4
239000000126 substance Substances 0.000 claims description 4
150000007513 acids Chemical class 0.000 claims description 3
125000003277 amino group Chemical group 0.000 claims description 3
125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 3
229910052739 hydrogen Inorganic materials 0.000 claims description 3
239000001257 hydrogen Substances 0.000 claims description 3
125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 3
125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 3
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical group C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 2
125000003545 alkoxy group Chemical group 0.000 claims description 2
125000000217 alkyl group Chemical group 0.000 claims description 2
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 2
201000010099 disease Diseases 0.000 claims description 2
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 2
239000003814 drug Substances 0.000 claims description 2
230000000771 oncological effect Effects 0.000 claims description 2
125000001909 leucine group Chemical group [H]N(*)C(C(*)=O)C([H])([H])C(C([H])([H])[H])C([H])([H])[H] 0.000 claims 3
125000001980 alanyl group Chemical group 0.000 claims 1
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 57
239000011347 resin Substances 0.000 description 23
229920005989 resin Polymers 0.000 description 23
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 19
239000000243 solution Substances 0.000 description 19
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
229940024606 amino acid Drugs 0.000 description 15
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 15
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 15
150000001413 amino acids Chemical class 0.000 description 14
230000015572 biosynthetic process Effects 0.000 description 11
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 10
238000003786 synthesis reaction Methods 0.000 description 10
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 9
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
125000006239 protecting group Chemical group 0.000 description 8
239000011541 reaction mixture Substances 0.000 description 8
230000002829 reductive effect Effects 0.000 description 8
238000006243 chemical reaction Methods 0.000 description 7
239000012634 fragment Substances 0.000 description 7
239000000203 mixture Substances 0.000 description 7
239000000047 product Substances 0.000 description 7
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
241000699670 Mus sp. Species 0.000 description 6
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 6
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 6
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 6
210000004027 cell Anatomy 0.000 description 6
239000003153 chemical reaction reagent Substances 0.000 description 6
238000001914 filtration Methods 0.000 description 6
229910052938 sodium sulfate Inorganic materials 0.000 description 6
235000011152 sodium sulphate Nutrition 0.000 description 6
239000002904 solvent Substances 0.000 description 6
125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 5
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
235000015165 citric acid Nutrition 0.000 description 5
238000000926 separation method Methods 0.000 description 5
238000012360 testing method Methods 0.000 description 5
125000000229 (C1-C4)alkoxy group Chemical group 0.000 description 4
LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 4
FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 4
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
150000001299 aldehydes Chemical class 0.000 description 4
230000037396 body weight Effects 0.000 description 4
NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 4
150000002576 ketones Chemical class 0.000 description 4
239000012044 organic layer Substances 0.000 description 4
229920000307 polymer substrate Polymers 0.000 description 4
238000005406 washing Methods 0.000 description 4
ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 3
LQKSHSFQQRCAFW-UHFFFAOYSA-N Dolastatin 15 Natural products COC1=CC(=O)N(C(=O)C(OC(=O)C2N(CCC2)C(=O)C2N(CCC2)C(=O)C(C(C)C)N(C)C(=O)C(NC(=O)C(C(C)C)N(C)C)C(C)C)C(C)C)C1CC1=CC=CC=C1 LQKSHSFQQRCAFW-UHFFFAOYSA-N 0.000 description 3
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
230000005526 G1 to G0 transition Effects 0.000 description 3
AKCRVYNORCOYQT-YFKPBYRVSA-N N-methyl-L-valine Chemical compound CN[C@@H](C(C)C)C(O)=O AKCRVYNORCOYQT-YFKPBYRVSA-N 0.000 description 3
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
LQKSHSFQQRCAFW-CCVNJFHASA-N [(2s)-1-[(2s)-2-benzyl-3-methoxy-5-oxo-2h-pyrrol-1-yl]-3-methyl-1-oxobutan-2-yl] (2s)-1-[(2s)-1-[(2s)-2-[[(2s)-2-[[(2s)-2-(dimethylamino)-3-methylbutanoyl]amino]-3-methylbutanoyl]-methylamino]-3-methylbutanoyl]pyrrolidine-2-carbonyl]pyrrolidine-2-carboxyl Chemical compound C([C@@H]1N(C(=O)C=C1OC)C(=O)[C@@H](OC(=O)[C@H]1N(CCC1)C(=O)[C@H]1N(CCC1)C(=O)[C@H](C(C)C)N(C)C(=O)[C@@H](NC(=O)[C@H](C(C)C)N(C)C)C(C)C)C(C)C)C1=CC=CC=C1 LQKSHSFQQRCAFW-CCVNJFHASA-N 0.000 description 3
201000011510 cancer Diseases 0.000 description 3
238000012512 characterization method Methods 0.000 description 3
239000012043 crude product Substances 0.000 description 3
VLNZUSMTOFYNPS-UHFFFAOYSA-N diethylphosphorylformonitrile Chemical compound CCP(=O)(CC)C#N VLNZUSMTOFYNPS-UHFFFAOYSA-N 0.000 description 3
108010045552 dolastatin 15 Proteins 0.000 description 3
238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 3
239000006260 foam Substances 0.000 description 3
238000001727 in vivo Methods 0.000 description 3
125000001998 leucyl group Chemical group 0.000 description 3
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
239000003921 oil Substances 0.000 description 3
238000010647 peptide synthesis reaction Methods 0.000 description 3
239000012071 phase Substances 0.000 description 3
229920000642 polymer Polymers 0.000 description 3
238000005932 reductive alkylation reaction Methods 0.000 description 3
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
UGNIYGNGCNXHTR-SFHVURJKSA-N (2s)-2-(9h-fluoren-9-ylmethoxycarbonylamino)-3-methylbutanoic acid Chemical compound C1=CC=C2C(COC(=O)N[C@@H](C(C)C)C(O)=O)C3=CC=CC=C3C2=C1 UGNIYGNGCNXHTR-SFHVURJKSA-N 0.000 description 2
CNPSFBUUYIVHAP-WHFBIAKZSA-N (2s,3s)-3-methylpyrrolidin-1-ium-2-carboxylate Chemical compound C[C@H]1CCN[C@@H]1C(O)=O CNPSFBUUYIVHAP-WHFBIAKZSA-N 0.000 description 2
MYRTYDVEIRVNKP-UHFFFAOYSA-N 1,2-Divinylbenzene Chemical compound C=CC1=CC=CC=C1C=C MYRTYDVEIRVNKP-UHFFFAOYSA-N 0.000 description 2
BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 description 2
JVSFQJZRHXAUGT-UHFFFAOYSA-N 2,2-dimethylpropanoyl chloride Chemical compound CC(C)(C)C(Cl)=O JVSFQJZRHXAUGT-UHFFFAOYSA-N 0.000 description 2
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
GKQLYSROISKDLL-UHFFFAOYSA-N EEDQ Chemical compound C1=CC=C2N(C(=O)OCC)C(OCC)C=CC2=C1 GKQLYSROISKDLL-UHFFFAOYSA-N 0.000 description 2
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
APGLTERDKORUHK-LURJTMIESA-N N,N-dimethyl-L-Valine Chemical compound CC(C)[C@H](N(C)C)C(O)=O APGLTERDKORUHK-LURJTMIESA-N 0.000 description 2
108010033276 Peptide Fragments Proteins 0.000 description 2
102000007079 Peptide Fragments Human genes 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
RHQDFWAXVIIEBN-UHFFFAOYSA-N Trifluoroethanol Chemical compound OCC(F)(F)F RHQDFWAXVIIEBN-UHFFFAOYSA-N 0.000 description 2
239000004480 active ingredient Substances 0.000 description 2
239000013543 active substance Substances 0.000 description 2
150000008064 anhydrides Chemical class 0.000 description 2
IADUEWIQBXOCDZ-UHFFFAOYSA-N azetidine-2-carboxylic acid Chemical compound OC(=O)C1CCN1 IADUEWIQBXOCDZ-UHFFFAOYSA-N 0.000 description 2
230000008901 benefit Effects 0.000 description 2
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 2
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 2
239000004305 biphenyl Substances 0.000 description 2
239000003054 catalyst Substances 0.000 description 2
239000003795 chemical substances by application Substances 0.000 description 2
238000004587 chromatography analysis Methods 0.000 description 2
238000001816 cooling Methods 0.000 description 2
238000010511 deprotection reaction Methods 0.000 description 2
BGRWYRAHAFMIBJ-UHFFFAOYSA-N diisopropylcarbodiimide Natural products CC(C)NC(=O)NC(C)C BGRWYRAHAFMIBJ-UHFFFAOYSA-N 0.000 description 2
MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 2
239000003937 drug carrier Substances 0.000 description 2
238000001035 drying Methods 0.000 description 2
230000000694 effects Effects 0.000 description 2
230000002255 enzymatic effect Effects 0.000 description 2
239000000284 extract Substances 0.000 description 2
239000000706 filtrate Substances 0.000 description 2
JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
239000010410 layer Substances 0.000 description 2
239000007788 liquid Substances 0.000 description 2
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 2
229930014626 natural product Natural products 0.000 description 2
125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
229910052763 palladium Inorganic materials 0.000 description 2
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 2
239000002244 precipitate Substances 0.000 description 2
230000008569 process Effects 0.000 description 2
238000000746 purification Methods 0.000 description 2
UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical compound OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 description 2
239000000376 reactant Substances 0.000 description 2
239000007787 solid Substances 0.000 description 2
239000007790 solid phase Substances 0.000 description 2
239000000725 suspension Substances 0.000 description 2
239000003826 tablet Substances 0.000 description 2
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
GNZSGDFUKQDBQB-ZAGFBCOMSA-N (2S,3S)-3-methyl-N-[[1-[(2S)-pyrrolidine-2-carbonyl]cyclohexa-2,4-dien-1-yl]methyl]pyrrolidine-2-carboxamide Chemical compound C[C@H]1CCN[C@@H]1C(=O)NCC2(CC=CC=C2)C(=O)[C@@H]3CCCN3 GNZSGDFUKQDBQB-ZAGFBCOMSA-N 0.000 description 1
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CANZBRDGRHNSGZ-NSHDSACASA-N (2s)-3-methyl-2-(phenylmethoxycarbonylamino)butanoic acid Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)OCC1=CC=CC=C1 CANZBRDGRHNSGZ-NSHDSACASA-N 0.000 description 1
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CNPSFBUUYIVHAP-AKGZTFGVSA-N (2s)-3-methylpyrrolidine-2-carboxylic acid Chemical compound CC1CCN[C@@H]1C(O)=O CNPSFBUUYIVHAP-AKGZTFGVSA-N 0.000 description 1
SZNKRADUZXAHCO-MERQFXBCSA-N (2s)-n-benzylpyrrolidine-2-carboxamide;hydrochloride Chemical compound Cl.O=C([C@H]1NCCC1)NCC1=CC=CC=C1 SZNKRADUZXAHCO-MERQFXBCSA-N 0.000 description 1
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ZIWHMENIDGOELV-IMJSIDKUSA-N (2s,4s)-4-fluoropyrrolidin-1-ium-2-carboxylate Chemical compound OC(=O)[C@@H]1C[C@H](F)CN1 ZIWHMENIDGOELV-IMJSIDKUSA-N 0.000 description 1
BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
PFKFTWBEEFSNDU-UHFFFAOYSA-N 1,1'-Carbonyldiimidazole Substances C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 1
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
FNQIGYRDLYROLW-UHFFFAOYSA-N 1-hydroxy-2h-1,2,3-benzotriazine Chemical compound C1=CC=C2N(O)NN=CC2=C1 FNQIGYRDLYROLW-UHFFFAOYSA-N 0.000 description 1
FPIRBHDGWMWJEP-UHFFFAOYSA-N 1-hydroxy-7-azabenzotriazole Chemical compound C1=CN=C2N(O)N=NC2=C1 FPIRBHDGWMWJEP-UHFFFAOYSA-N 0.000 description 1
AHDSRXYHVZECER-UHFFFAOYSA-N 2,4,6-tris[(dimethylamino)methyl]phenol Chemical compound CN(C)CC1=CC(CN(C)C)=C(O)C(CN(C)C)=C1 AHDSRXYHVZECER-UHFFFAOYSA-N 0.000 description 1
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/08—Peptides having 5 to 11 amino acids
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/10—Tetrapeptides
- C07K5/1002—Tetrapeptides with the first amino acid being neutral
- C07K5/1005—Tetrapeptides with the first amino acid being neutral and aliphatic
- C07K5/101—Tetrapeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms, e.g. Val, Ile, Leu
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides

Landscapes

Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Organic Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
Medicinal Chemistry (AREA)
General Health & Medical Sciences (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Biochemistry (AREA)
Molecular Biology (AREA)
Genetics & Genomics (AREA)
Biophysics (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
Animal Behavior & Ethology (AREA)
Pharmacology & Pharmacy (AREA)
Immunology (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Gastroenterology & Hepatology (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Epidemiology (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Peptides Or Proteins (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)

HR08/472,453A 1995-06-07 1996-06-06 Novel compounds, the preparation and use thereof HRP960277A2 (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US08/472,453 US5831002A (en)	1992-05-20	1995-06-07	Antitumor peptides

Publications (1)

Publication Number	Publication Date
HRP960277A2 true HRP960277A2 (en)	1997-10-31

Family

ID=23875567

Family Applications (2)

Application Number	Title	Priority Date	Filing Date
HR08/472,453A HRP960277A2 (en)	1995-06-07	1996-06-06	Novel compounds, the preparation and use thereof
HR08/472,453A HRP960257A2 (en)	1995-06-07	1996-06-06	New compounds, their preparation and use

Family Applications After (1)

Application Number	Title	Priority Date	Filing Date
HR08/472,453A HRP960257A2 (en)	1995-06-07	1996-06-06	New compounds, their preparation and use

Country Status (33)

Country	Link
US (1)	US5831002A (fr)
EP (2)	EP0871656B1 (fr)
JP (2)	JP4221062B2 (fr)
KR (2)	KR100437985B1 (fr)
CN (2)	CN1182154C (fr)
AR (2)	AR003136A1 (fr)
AT (2)	ATE224910T1 (fr)
AU (2)	AU725164B2 (fr)
BG (2)	BG102125A (fr)
BR (2)	BR9609424A (fr)
CA (2)	CA2219818C (fr)
CO (2)	CO4700527A1 (fr)
CZ (2)	CZ293683B6 (fr)
DE (2)	DE69623472T2 (fr)
DK (2)	DK0871656T3 (fr)
ES (2)	ES2186783T3 (fr)
HR (2)	HRP960277A2 (fr)
HU (2)	HU228071B1 (fr)
IL (2)	IL122216A (fr)
MX (2)	MX9709147A (fr)
MY (2)	MY119042A (fr)
NO (2)	NO317670B1 (fr)
NZ (2)	NZ310444A (fr)
PL (2)	PL185763B1 (fr)
PT (2)	PT832104E (fr)
RO (2)	RO119783B1 (fr)
SI (2)	SI0832104T1 (fr)
SK (1)	SK282466B6 (fr)
TR (2)	TR199701544T1 (fr)
TW (2)	TW508357B (fr)
UA (2)	UA46775C2 (fr)
WO (2)	WO1996040751A1 (fr)
ZA (2)	ZA964710B (fr)

Families Citing this family (30)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5807984A (en) *	1995-11-09	1998-09-15	Basf Aktienegesellschaft	Oligopeptides, the preparation and use thereof
US20010009901A1 (en) *	1996-12-11	2001-07-26	Basf Aktiengesellschaft Germany	Antineoplastic peptides
TW474946B (en) *	1995-12-15	2002-02-01	Basf Ag	Novel compounds, the preparation and use thereof
US5965537A (en) *	1997-03-10	1999-10-12	Basf Aktiengesellschaft	Dolastatin 15 derivatives with carbonyl and heterocyclic functionalities at the C-terminus
US6103698A (en) *	1997-03-13	2000-08-15	Basf Aktiengesellschaft	Dolastatin-15 derivatives in combination with taxanes
US6143721A (en) *	1997-07-18	2000-11-07	Basf Aktiengesellschaft	Dolastatin 15 derivatives
US6015790A (en) *	1997-10-06	2000-01-18	Basf Aktiengesellschaft	Methods and compositions for treating rheumatoid arthritis
US5985837A (en) *	1998-07-08	1999-11-16	Basf Aktiengesellschaft	Dolastatin 15 derivatives
WO2000051998A1 (fr)	1999-03-02	2000-09-08	Boehringer Ingelheim Pharmaceuticals, Inc.	Composes utiles en tant qu'inhibiteurs reversibles de la cathepsine s
US6420364B1 (en)	1999-09-13	2002-07-16	Boehringer Ingelheim Pharmaceuticals, Inc.	Compound useful as reversible inhibitors of cysteine proteases
JP4776843B2 (ja)	1999-10-01	2011-09-21	イムノゲンインコーポレーティッド	免疫複合体及び化学療法剤を用いる癌治療用組成物及び方法
WO2002088298A1 (fr)	2001-04-27	2002-11-07	The Procter & Gamble Company	Composes, compositions et procedes permettant de reguler des films biologiques
AU2002359792A1 (en) *	2001-12-18	2003-06-30	Proteologics, Inc.	Methods and compositions for the inhibition of viral release
EP1531846A4 (fr) *	2002-02-27	2006-04-19	Us Gov Health & Human Serv	Conjugues de ligand, adaptateur et agent cytotoxique, compositions associees et procedes d'utilisation relatifs
EP1781310B1 (fr)	2004-08-02	2015-10-14	Ramot at Tel Aviv University Ltd.	Articles de nanostructures a base de peptides et leur procede de formation
WO2006122408A1 (fr)	2005-05-18	2006-11-23	Aegera Therapeutics Inc.	Composes liants de domaine bir
JP2009504751A (ja) *	2005-08-19	2009-02-05	アメリカ合衆国	ヒストンデアセチラーゼ阻害薬の局所製剤及びその使用方法
WO2007043048A2 (fr) *	2005-10-11	2007-04-19	Ramot At Tel Aviv University Ltd.	Hydrogels auto-assembles et leurs procedes d'elaboration et d'utilisation
MY159563A (en)	2006-05-16	2017-01-13	Pharmascience Inc	Iap bir domain binding compounds
WO2008014252A2 (fr) *	2006-07-24	2008-01-31	Tetralogic Pharmaceuticals Corporation	Inhibiteurs des iap
US7985879B2 (en)	2007-04-12	2011-07-26	Scinopharm Taiwan Ltd.	Process for making galantamine
UY32099A (es)	2008-09-11	2010-04-30	Enanta Pharm Inc	Inhibidores macrocíclicos de serina proteasas de hepatitis c
US8283372B2 (en)	2009-07-02	2012-10-09	Tetralogic Pharmaceuticals Corp.	2-(1H-indol-3-ylmethyl)-pyrrolidine dimer as a SMAC mimetic
SG182724A1 (en)	2010-02-12	2012-08-30	Pharmascience Inc	Iap bir domain binding compounds
US8937041B2 (en)	2010-12-30	2015-01-20	Abbvie, Inc.	Macrocyclic hepatitis C serine protease inhibitors
KR20140003521A (ko)	2010-12-30	2014-01-09	이난타 파마슈티칼스, 인코포레이티드	페난트리딘 매크로사이클릭 ｃ형 간염 세린 프로테아제 억제제
US10201584B1 (en)	2011-05-17	2019-02-12	Abbvie Inc.	Compositions and methods for treating HCV
CN113527414A (zh) *	2011-05-27	2021-10-22	Ambrx公司	含有非天然氨基酸连接的海兔毒素衍生物的组合物、涉及该海兔毒素衍生物的方法及其用途
WO2015103490A1 (fr)	2014-01-03	2015-07-09	Abbvie, Inc.	Formes galéniques antivirales solides
JPWO2023033129A1 (fr)	2021-09-03	2023-03-09

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4816444A (en) *	1987-07-10	1989-03-28	Arizona Board Of Regents, Arizona State University	Cell growth inhibitory substance
US4879278A (en) *	1989-05-16	1989-11-07	Arizona Board Of Regents	Isolation and structural elucidation of the cytostatic linear depsipeptide dolastatin 15
EP0934950B1 (fr) *	1991-08-09	2002-04-10	Teikoku Hormone Mfg. Co., Ltd.	Derivé de tetrapeptide
ATE169637T1 (de) *	1992-05-20	1998-08-15	Basf Ag	Derivate des dolastatin
US5530097A (en) *	1994-08-01	1996-06-25	Arizona Board Of Regents Acting On Behalf Of Arizona State University	Human cancer inhibitory peptide amides
US5504191A (en) *	1994-08-01	1996-04-02	Arizona Board Of Regents Acting On Behalf Of Arizona State University	Human cancer inhibitory pentapeptide methyl esters

1995
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Also Published As

Publication number	Publication date
SI0871656T1 (en)	2003-08-31
CA2219819C (fr)	2008-05-20
CA2219819A1 (fr)	1996-12-19
MX9709147A (es)	1998-03-31
RO119783B1 (ro)	2005-03-30
TW508357B (en)	2002-11-01
EP0871656A1 (fr)	1998-10-21
NO975711D0 (no)	1997-12-05
HRP960257A2 (en)	1998-02-28
IL122215A (en)	2001-08-26
SK282466B6 (sk)	2002-02-05
TW424096B (en)	2001-03-01
PT871656E (pt)	2002-12-31
PL185762B1 (pl)	2003-07-31
NO975710L (no)	1998-02-02
CZ293683B6 (cs)	2004-07-14
BR9609423A (pt)	1999-06-29
CN1187198A (zh)	1998-07-08
CZ376597A3 (cs)	1998-06-17
CN1182154C (zh)	2004-12-29
BR9609424A (pt)	2000-03-28
NO975711L (no)	1998-01-30
PL323726A1 (en)	1998-04-14
MY119042A (en)	2005-03-31
JP3957751B2 (ja)	2007-08-15
DE69623992T2 (de)	2003-05-22
PL185763B1 (pl)	2003-07-31
IL122215A0 (en)	1998-04-05
ES2188759T3 (es)	2003-07-01
PT832104E (pt)	2002-12-31
TR199701545T1 (xx)	1998-04-21
NZ310444A (en)	1999-11-29
KR100437986B1 (ko)	2004-09-18
CZ293682B6 (cs)	2004-07-14
JPH11504653A (ja)	1999-04-27
CZ376397A3 (cs)	1998-06-17
WO1996040751A1 (fr)	1996-12-19
SK165397A3 (en)	1998-10-07
NO318384B1 (no)	2005-03-14
BG102125A (en)	1998-09-30
MX9709146A (es)	1998-03-31
MY124487A (en)	2006-06-30
ZA964711B (en)	1997-12-08
CA2219818A1 (fr)	1996-12-19
BG102152A (en)	1998-09-30
ES2186783T3 (es)	2003-05-16
SI0832104T1 (en)	2003-08-31
JPH11504652A (ja)	1999-04-27
DK0871656T3 (da)	2003-01-27
AR003136A1 (es)	1998-07-08
AU6124296A (en)	1996-12-30
HUP9801817A3 (en)	1999-06-28
EP0832104A1 (fr)	1998-04-01
DE69623992D1 (de)	2002-10-31
HUP9801910A3 (en)	1999-06-28
CN1182153C (zh)	2004-12-29
DE69623472D1 (de)	2002-10-10
CO4700527A1 (es)	1998-12-29
AU6124196A (en)	1996-12-30
AU725170B2 (en)	2000-10-05
KR19990022582A (ko)	1999-03-25
AR003427A1 (es)	1998-08-05
HU228073B1 (hu)	2012-09-28
CA2219818C (fr)	2008-05-20
EP0832104B1 (fr)	2002-09-04
UA46775C2 (uk)	2002-06-17
IL122216A (en)	2002-02-10
KR19990022583A (ko)	1999-03-25
HUP9801910A2 (hu)	1999-01-28
US5831002A (en)	1998-11-03
WO1996040752A1 (fr)	1996-12-19
JP4221062B2 (ja)	2009-02-12
HU228071B1 (hu)	2012-09-28
PL323723A1 (en)	1998-04-14
ATE224910T1 (de)	2002-10-15
RO118953B1 (ro)	2004-01-30
ATE223431T1 (de)	2002-09-15
CN1187199A (zh)	1998-07-08
UA46776C2 (uk)	2002-06-17
ZA964710B (en)	1997-12-08
CO4700526A1 (es)	1998-12-29
KR100437985B1 (ko)	2004-09-18
NZ310443A (en)	1999-10-28
TR199701544T1 (xx)	1998-03-21
DK0832104T3 (da)	2003-01-06
DE69623472T2 (de)	2003-08-21
AU725164B2 (en)	2000-10-05
EP0871656B1 (fr)	2002-09-25
IL122216A0 (en)	1998-04-05
NO975710D0 (no)	1997-12-05
HUP9801817A2 (hu)	1998-11-30
NO317670B1 (no)	2004-11-29

Publication	Publication Date	Title
HRP960277A2 (en)	1997-10-31	Novel compounds, the preparation and use thereof
EP0674652B1 (fr)	2000-09-13	Analogue de dolastatine
EP0642530B1 (fr)	1998-08-12	Derives de dolastatine
AU2004220772B2 (en)	2008-06-12	Antineoplastic peptides
AU775090B2 (en)	2004-07-15	Antineoplastic peptides
SK282467B6 (sk)	2002-02-05	Peptidy, farmaceutický prostriedok s ich obsahom a ich použitie

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2002-06-06	ODRP	Renewal fee for the maintenance of a patent	Payment date: 20020606 Year of fee payment: 7
2003-04-09	ODBC	Application rejected