ES2621672T3 - Derivados de 1-[1-(benzoil)-pirrolidin-2-carbonil]-pirrolidin-2-carbonitrilo - Google Patents
Derivados de 1-[1-(benzoil)-pirrolidin-2-carbonil]-pirrolidin-2-carbonitrilo Download PDFInfo
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- ES2621672T3 ES2621672T3 ES13794837.8T ES13794837T ES2621672T3 ES 2621672 T3 ES2621672 T3 ES 2621672T3 ES 13794837 T ES13794837 T ES 13794837T ES 2621672 T3 ES2621672 T3 ES 2621672T3
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- Prior art keywords
- pyrrolidin
- formula
- carbonyl
- compound
- carbonitrile
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- OACPBABDSINWMY-UHFFFAOYSA-N 1-(1-benzoylpyrrolidine-2-carbonyl)pyrrolidine-2-carbonitrile Chemical class C1CCC(C#N)N1C(=O)C1CCCN1C(=O)C1=CC=CC=C1 OACPBABDSINWMY-UHFFFAOYSA-N 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 150
- 150000003839 salts Chemical class 0.000 claims abstract description 35
- -1 benzyloxy, phenylcarbonyloxy, naphthylcarbonyloxy, quinolinylcarbonyloxy, isoquinolinylcarbonyloxy Chemical group 0.000 claims abstract description 34
- 239000012453 solvate Substances 0.000 claims abstract description 24
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 15
- 239000001257 hydrogen Substances 0.000 claims abstract description 15
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 12
- 239000011737 fluorine Chemical group 0.000 claims abstract description 12
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 11
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims abstract description 10
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 10
- 150000002367 halogens Chemical class 0.000 claims abstract description 10
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 9
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims abstract description 7
- 125000005196 alkyl carbonyloxy group Chemical group 0.000 claims abstract description 7
- 150000002825 nitriles Chemical group 0.000 claims abstract description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 6
- 125000004414 alkyl thio group Chemical group 0.000 claims abstract description 5
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 5
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 3
- 150000002431 hydrogen Chemical group 0.000 claims abstract 3
- 238000000034 method Methods 0.000 claims description 74
- 238000006243 chemical reaction Methods 0.000 claims description 34
- 208000010877 cognitive disease Diseases 0.000 claims description 30
- 238000011282 treatment Methods 0.000 claims description 27
- 239000003814 drug Substances 0.000 claims description 24
- 208000024827 Alzheimer disease Diseases 0.000 claims description 16
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 14
- 201000010099 disease Diseases 0.000 claims description 12
- 239000008194 pharmaceutical composition Substances 0.000 claims description 11
- 208000018737 Parkinson disease Diseases 0.000 claims description 10
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 10
- 238000002360 preparation method Methods 0.000 claims description 10
- 208000019022 Mood disease Diseases 0.000 claims description 6
- 125000001153 fluoro group Chemical group F* 0.000 claims description 6
- 230000008569 process Effects 0.000 claims description 6
- 208000017194 Affective disease Diseases 0.000 claims description 5
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 5
- 239000002671 adjuvant Substances 0.000 claims description 4
- 201000000980 schizophrenia Diseases 0.000 claims description 4
- RYGXYKCVBXEBDI-PMACEKPBSA-N (2s)-1-[(2s)-1-(3,5-dimethoxy-4-phenylmethoxybenzoyl)-4,4-difluoropyrrolidine-2-carbonyl]pyrrolidine-2-carbonitrile Chemical compound COC1=CC(C(=O)N2[C@@H](CC(F)(F)C2)C(=O)N2[C@@H](CCC2)C#N)=CC(OC)=C1OCC1=CC=CC=C1 RYGXYKCVBXEBDI-PMACEKPBSA-N 0.000 claims description 3
- KPMLPBXDOBSUBP-ICSRJNTNSA-N (2s)-1-[(2s)-4,4-difluoro-1-(2-phenylmethoxybenzoyl)pyrrolidine-2-carbonyl]pyrrolidine-2-carbonitrile Chemical compound N1([C@@H](CC(C1)(F)F)C(=O)N1[C@@H](CCC1)C#N)C(=O)C1=CC=CC=C1OCC1=CC=CC=C1 KPMLPBXDOBSUBP-ICSRJNTNSA-N 0.000 claims description 3
- VCSMTBMNSODAQC-ICSRJNTNSA-N (2s)-1-[(2s)-4,4-difluoro-1-(3-fluoro-4-phenylmethoxybenzoyl)pyrrolidine-2-carbonyl]pyrrolidine-2-carbonitrile Chemical compound FC1=CC(C(=O)N2[C@@H](CC(F)(F)C2)C(=O)N2[C@@H](CCC2)C#N)=CC=C1OCC1=CC=CC=C1 VCSMTBMNSODAQC-ICSRJNTNSA-N 0.000 claims description 3
- QLLULSSJXPMAQO-FPOVZHCZSA-N (2s)-1-[(2s)-4,4-difluoro-1-(3-phenylmethoxybenzoyl)pyrrolidine-2-carbonyl]pyrrolidine-2-carbonitrile Chemical compound N1([C@@H](CC(C1)(F)F)C(=O)N1[C@@H](CCC1)C#N)C(=O)C(C=1)=CC=CC=1OCC1=CC=CC=C1 QLLULSSJXPMAQO-FPOVZHCZSA-N 0.000 claims description 3
- LMPUBXCJEKFGPN-FPOVZHCZSA-N (2s)-1-[(2s)-4,4-difluoro-1-(4-phenylmethoxybenzoyl)pyrrolidine-2-carbonyl]pyrrolidine-2-carbonitrile Chemical compound N1([C@@H](CC(C1)(F)F)C(=O)N1[C@@H](CCC1)C#N)C(=O)C(C=C1)=CC=C1OCC1=CC=CC=C1 LMPUBXCJEKFGPN-FPOVZHCZSA-N 0.000 claims description 3
- LRDQXWIEHOWLMQ-UIOOFZCWSA-N (2s)-1-[(2s)-4,4-difluoro-1-[3-methoxy-4,5-bis(phenylmethoxy)benzoyl]pyrrolidine-2-carbonyl]pyrrolidine-2-carbonitrile Chemical compound C=1C=CC=CC=1COC=1C(OC)=CC(C(=O)N2[C@@H](CC(F)(F)C2)C(=O)N2[C@@H](CCC2)C#N)=CC=1OCC1=CC=CC=C1 LRDQXWIEHOWLMQ-UIOOFZCWSA-N 0.000 claims description 3
- KYOISHPHSGUAGP-ICSRJNTNSA-N (2s)-1-[(2s)-4,4-difluoro-1-[4-phenylmethoxy-3-(trifluoromethyl)benzoyl]pyrrolidine-2-carbonyl]pyrrolidine-2-carbonitrile Chemical compound FC(F)(F)C1=CC(C(=O)N2[C@@H](CC(F)(F)C2)C(=O)N2[C@@H](CCC2)C#N)=CC=C1OCC1=CC=CC=C1 KYOISHPHSGUAGP-ICSRJNTNSA-N 0.000 claims description 3
- PJTLPDJXGHLYQJ-VXNXHJTFSA-N (2s)-1-[(2s,4r)-1-(3,5-dimethoxy-4-phenylmethoxybenzoyl)-4-[(2-methylpropan-2-yl)oxy]pyrrolidine-2-carbonyl]pyrrolidine-2-carbonitrile Chemical compound COC1=CC(C(=O)N2[C@@H](C[C@H](C2)OC(C)(C)C)C(=O)N2[C@@H](CCC2)C#N)=CC(OC)=C1OCC1=CC=CC=C1 PJTLPDJXGHLYQJ-VXNXHJTFSA-N 0.000 claims description 3
- VPSURWWYROJTIQ-HKBOAZHASA-N (2s)-1-[(2s,4r)-1-(3,5-dimethoxy-4-phenylmethoxybenzoyl)-4-fluoropyrrolidine-2-carbonyl]pyrrolidine-2-carbonitrile Chemical compound COC1=CC(C(=O)N2[C@@H](C[C@@H](F)C2)C(=O)N2[C@@H](CCC2)C#N)=CC(OC)=C1OCC1=CC=CC=C1 VPSURWWYROJTIQ-HKBOAZHASA-N 0.000 claims description 3
- CDCQFMSWVXKTEI-BDTNDASRSA-N (2s)-1-[(2s,4r)-1-(3,5-dimethoxy-4-phenylmethoxybenzoyl)-4-methoxypyrrolidine-2-carbonyl]pyrrolidine-2-carbonitrile Chemical compound N1([C@@H](C[C@H](C1)OC)C(=O)N1[C@@H](CCC1)C#N)C(=O)C(C=C1OC)=CC(OC)=C1OCC1=CC=CC=C1 CDCQFMSWVXKTEI-BDTNDASRSA-N 0.000 claims description 3
- ZQMKYRBZMXCHDG-NYVOZVTQSA-N (2s)-1-[(2s,4s)-1-(3,5-dimethoxy-4-phenylmethoxybenzoyl)-4-methylpyrrolidine-2-carbonyl]pyrrolidine-2-carbonitrile Chemical compound COC1=CC(C(=O)N2[C@@H](C[C@H](C)C2)C(=O)N2[C@@H](CCC2)C#N)=CC(OC)=C1OCC1=CC=CC=C1 ZQMKYRBZMXCHDG-NYVOZVTQSA-N 0.000 claims description 3
- MMJWMBIKUUAUNB-PVHODMMVSA-N (2s)-1-[(2s,4s)-1-(3,5-dimethoxy-4-phenylmethoxybenzoyl)-4-phenylpyrrolidine-2-carbonyl]pyrrolidine-2-carbonitrile Chemical compound COC1=CC(C(=O)N2[C@@H](C[C@H](C2)C=2C=CC=CC=2)C(=O)N2[C@@H](CCC2)C#N)=CC(OC)=C1OCC1=CC=CC=C1 MMJWMBIKUUAUNB-PVHODMMVSA-N 0.000 claims description 3
- QHNGZPUFJVCMAC-BVSLBCMMSA-N (3r,5s)-5-[(2s)-2-cyanopyrrolidine-1-carbonyl]-1-(3,5-dimethoxy-4-phenylmethoxybenzoyl)pyrrolidine-3-carbonitrile Chemical compound COC1=CC(C(=O)N2[C@@H](C[C@H](C2)C#N)C(=O)N2[C@@H](CCC2)C#N)=CC(OC)=C1OCC1=CC=CC=C1 QHNGZPUFJVCMAC-BVSLBCMMSA-N 0.000 claims description 3
- OJHYGPLZPJPRLJ-ZRBLBEILSA-N [(3r,5s)-5-[(2s)-2-cyanopyrrolidine-1-carbonyl]-1-(3,5-dimethoxy-4-phenylmethoxybenzoyl)pyrrolidin-3-yl] acetate Chemical compound COC1=CC(C(=O)N2[C@@H](C[C@H](C2)OC(C)=O)C(=O)N2[C@@H](CCC2)C#N)=CC(OC)=C1OCC1=CC=CC=C1 OJHYGPLZPJPRLJ-ZRBLBEILSA-N 0.000 claims description 3
- KSFXJICZZKTAJC-ZEQRLZLVSA-N [2-benzoyloxy-5-[(2s)-2-[(2s)-2-cyanopyrrolidine-1-carbonyl]-4,4-difluoropyrrolidine-1-carbonyl]-3-methoxyphenyl] benzoate Chemical compound C=1C=CC=CC=1C(=O)OC=1C(OC)=CC(C(=O)N2[C@@H](CC(F)(F)C2)C(=O)N2[C@@H](CCC2)C#N)=CC=1OC(=O)C1=CC=CC=C1 KSFXJICZZKTAJC-ZEQRLZLVSA-N 0.000 claims description 3
- SLXVGFMNHXEBEB-GJZGRUSLSA-N [4-[(2s)-2-[(2s)-2-cyanopyrrolidine-1-carbonyl]-4,4-difluoropyrrolidine-1-carbonyl]-2,6-dimethoxyphenyl] acetate Chemical compound COC1=C(OC(C)=O)C(OC)=CC(C(=O)N2[C@@H](CC(F)(F)C2)C(=O)N2[C@@H](CCC2)C#N)=C1 SLXVGFMNHXEBEB-GJZGRUSLSA-N 0.000 claims description 3
- AKPQWPSPFZAOLD-OALUTQOASA-N [4-[(2s)-2-[(2s)-2-cyanopyrrolidine-1-carbonyl]-4,4-difluoropyrrolidine-1-carbonyl]-2,6-dimethoxyphenyl] benzoate Chemical compound COC1=CC(C(=O)N2[C@@H](CC(F)(F)C2)C(=O)N2[C@@H](CCC2)C#N)=CC(OC)=C1OC(=O)C1=CC=CC=C1 AKPQWPSPFZAOLD-OALUTQOASA-N 0.000 claims description 3
- UNRZBJNUJBINFC-HOTGVXAUSA-N [5-[(2s)-2-[(2s)-2-cyanopyrrolidine-1-carbonyl]-4,4-difluoropyrrolidine-1-carbonyl]-2,3-dimethoxyphenyl] 2,2-dimethylpropanoate Chemical compound CC(C)(C)C(=O)OC1=C(OC)C(OC)=CC(C(=O)N2[C@@H](CC(F)(F)C2)C(=O)N2[C@@H](CCC2)C#N)=C1 UNRZBJNUJBINFC-HOTGVXAUSA-N 0.000 claims description 3
- AOCAMLSIPXYBHW-GJZGRUSLSA-N [5-[(2s)-2-[(2s)-2-cyanopyrrolidine-1-carbonyl]-4,4-difluoropyrrolidine-1-carbonyl]-2,3-dimethoxyphenyl] acetate Chemical compound CC(=O)OC1=C(OC)C(OC)=CC(C(=O)N2[C@@H](CC(F)(F)C2)C(=O)N2[C@@H](CCC2)C#N)=C1 AOCAMLSIPXYBHW-GJZGRUSLSA-N 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
- 238000011321 prophylaxis Methods 0.000 claims description 3
- NGNSKOONGZXUQW-ACRUOGEOSA-N (2s)-1-[(2s,4s)-1-(3,5-dimethoxy-4-phenylmethoxybenzoyl)-4-(trifluoromethyl)pyrrolidine-2-carbonyl]pyrrolidine-2-carbonitrile Chemical compound COC1=CC(C(=O)N2[C@@H](C[C@@H](C2)C(F)(F)F)C(=O)N2[C@@H](CCC2)C#N)=CC(OC)=C1OCC1=CC=CC=C1 NGNSKOONGZXUQW-ACRUOGEOSA-N 0.000 claims description 2
- 125000005392 carboxamide group Chemical group NC(=O)* 0.000 claims description 2
- 125000002560 nitrile group Chemical group 0.000 claims description 2
- 102000056251 Prolyl Oligopeptidases Human genes 0.000 description 77
- 101001095266 Homo sapiens Prolyl endopeptidase Proteins 0.000 description 75
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 54
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 48
- 239000000243 solution Substances 0.000 description 48
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- 239000003112 inhibitor Substances 0.000 description 28
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 27
- 238000004007 reversed phase HPLC Methods 0.000 description 26
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 25
- 230000008878 coupling Effects 0.000 description 25
- 229930182821 L-proline Natural products 0.000 description 23
- RDRBIXSNGAYLPT-UHFFFAOYSA-N CC1=CC=C(COC2=CC3=C(C=C2)C(NC(=O)OCC2C4=C(C=CC=C4)C4=C2C=CC=C4)C2=C(O3)C=CC=C2)C=C1 Chemical compound CC1=CC=C(COC2=CC3=C(C=C2)C(NC(=O)OCC2C4=C(C=CC=C4)C4=C2C=CC=C4)C2=C(O3)C=CC=C2)C=C1 RDRBIXSNGAYLPT-UHFFFAOYSA-N 0.000 description 22
- ZPGDWQNBZYOZTI-SFHVURJKSA-N (2s)-1-(9h-fluoren-9-ylmethoxycarbonyl)pyrrolidine-2-carboxylic acid Chemical compound OC(=O)[C@@H]1CCCN1C(=O)OCC1C2=CC=CC=C2C2=CC=CC=C21 ZPGDWQNBZYOZTI-SFHVURJKSA-N 0.000 description 21
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- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 19
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- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 16
- 239000002253 acid Substances 0.000 description 16
- 150000001412 amines Chemical class 0.000 description 16
- 239000011347 resin Substances 0.000 description 16
- 229920005989 resin Polymers 0.000 description 16
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 15
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
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- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 14
- 239000003960 organic solvent Substances 0.000 description 14
- 230000015572 biosynthetic process Effects 0.000 description 13
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- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 13
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- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/16—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- 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
-
- 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
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- 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
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
- Psychology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyrrole Compounds (AREA)
- Epidemiology (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP12382446 | 2012-11-12 | ||
| EP12382446.8A EP2730571A1 (en) | 2012-11-12 | 2012-11-12 | 1-[1-(benzoyl)-pyrrolidine-2-carbonyl]-pyrrolidine-2-carbonitrile derivatives |
| PCT/EP2013/073460 WO2014072498A1 (en) | 2012-11-12 | 2013-11-11 | 1-[1-(benzoyl)-pyrrolidine-2-carbonyl]-pyrrolidine-2-carbonitrile derivatives |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2621672T3 true ES2621672T3 (es) | 2017-07-04 |
Family
ID=47278735
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES13794837.8T Active ES2621672T3 (es) | 2012-11-12 | 2013-11-11 | Derivados de 1-[1-(benzoil)-pirrolidin-2-carbonil]-pirrolidin-2-carbonitrilo |
Country Status (25)
| Country | Link |
|---|---|
| US (2) | US10125097B2 (OSRAM) |
| EP (2) | EP2730571A1 (OSRAM) |
| JP (1) | JP6203278B2 (OSRAM) |
| KR (1) | KR102151290B1 (OSRAM) |
| CN (1) | CN104903314B (OSRAM) |
| AU (1) | AU2013343430B2 (OSRAM) |
| BR (1) | BR112015010377A8 (OSRAM) |
| CA (1) | CA2890042C (OSRAM) |
| CY (1) | CY1118818T1 (OSRAM) |
| DK (1) | DK2917209T3 (OSRAM) |
| EA (1) | EA028422B1 (OSRAM) |
| ES (1) | ES2621672T3 (OSRAM) |
| HR (1) | HRP20170485T1 (OSRAM) |
| HU (1) | HUE032472T2 (OSRAM) |
| LT (1) | LT2917209T (OSRAM) |
| ME (1) | ME02706B (OSRAM) |
| MX (1) | MX367488B (OSRAM) |
| NZ (1) | NZ709096A (OSRAM) |
| PL (1) | PL2917209T3 (OSRAM) |
| PT (1) | PT2917209T (OSRAM) |
| RS (1) | RS55865B1 (OSRAM) |
| SI (1) | SI2917209T1 (OSRAM) |
| SM (1) | SMT201700202T1 (OSRAM) |
| WO (1) | WO2014072498A1 (OSRAM) |
| ZA (1) | ZA201504269B (OSRAM) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2730571A1 (en) | 2012-11-12 | 2014-05-14 | Universitat De Barcelona | 1-[1-(benzoyl)-pyrrolidine-2-carbonyl]-pyrrolidine-2-carbonitrile derivatives |
| EP3031458A1 (en) * | 2014-12-09 | 2016-06-15 | Iproteos S.L. | Use of 1-[(2-phenylcycloprop-1-yl)carbonyl]-2-[(1,3-thiazolidin-3-yl)carbonyl]perhydroindole in the treatment of schizophrenia-associated cognitive deficits |
| IL275333B2 (en) | 2017-12-15 | 2023-09-01 | Praxis Biotech LLC | Inhibitors of fibroblast activation protein |
| US11504364B2 (en) | 2018-12-21 | 2022-11-22 | Praxis Biotech LLC | Inhibitors of fibroblast activation protein |
| BR112023000335A2 (pt) | 2020-07-07 | 2023-01-31 | Accure Therapeutics S L | 1-[1-(4-benzilóxi-3,5-diflúor-benzoil)-4-flúor-pirrolidina-2-carbonil]-pirrolidina-2-carbonitrila |
| MY208099A (en) * | 2020-12-28 | 2025-04-15 | Sarawak Biodiversity Council | Compound for treating neurodegenerative diseases and its isolation method thereof |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0536163A1 (en) * | 1990-06-04 | 1993-04-14 | Pfizer Inc. | Aromatic pyrrolidine and thiazolidine amides |
| US6159938A (en) | 1994-11-21 | 2000-12-12 | Cortech, Inc. | Serine protease inhibitors comprising α-keto heterocycles |
| HUT76640A (en) * | 1995-08-17 | 1997-10-28 | Chinoin Gyogyszer Es Vegyeszet | Compounds of pharmaceutical activity cyclic amide derivatives, pharmaceutical compositions containing them, process for producing them and their use |
| DE19603510A1 (de) | 1996-02-01 | 1997-08-07 | Knoell Hans Forschung Ev | Die Verwendung von Terrecyclolsäure A und Terrecyclolsäure A-Derivate als neue Inhibitoren der humanen Prolyl-Oligopeptidase |
| KR100568841B1 (ko) * | 2000-07-19 | 2006-04-10 | 에프. 호프만-라 로슈 아게 | 엔도텔린-전환 효소의 억제제로서의 피롤리딘 유도체 |
| FI20011466A0 (fi) | 2001-07-04 | 2001-07-04 | Orion Corp | Prolyylioligopeptidaasia inhiboivaa aktiivisuutta omaavia yhdisteitä, niiden valmistusmenetelmiä ja käyttö |
| FI20030014A0 (fi) * | 2003-01-03 | 2003-01-03 | Orion Corp | Prolyylioligopeptidaasia inhiboivaa aktiivisuutta omaavia yhdisteitä |
| FI20031018A0 (fi) | 2003-07-04 | 2003-07-04 | Orion Corp | Parannus aivovammasta toipumiseen |
| JP4630192B2 (ja) | 2003-09-24 | 2011-02-09 | 日本化薬株式会社 | プロリルオリゴペプチダーゼ阻害剤 |
| US7667044B2 (en) | 2003-11-03 | 2010-02-23 | Probiodrug Ag | Compounds for the treatment of neurological disorders |
| EP1760076A1 (en) * | 2005-09-02 | 2007-03-07 | Ferring B.V. | FAP Inhibitors |
| ES2302473B1 (es) | 2006-12-22 | 2009-06-12 | Universidad De Barcelona | Agente terapeutico para el tratamiento del desorden afectivo bipolar en mamiferos. |
| US20120053222A1 (en) * | 2009-01-23 | 2012-03-01 | Mark Gorrell | Novel Metabolic Disease Therapy |
| EP2730571A1 (en) | 2012-11-12 | 2014-05-14 | Universitat De Barcelona | 1-[1-(benzoyl)-pyrrolidine-2-carbonyl]-pyrrolidine-2-carbonitrile derivatives |
-
2012
- 2012-11-12 EP EP12382446.8A patent/EP2730571A1/en not_active Withdrawn
-
2013
- 2013-11-11 SI SI201330601A patent/SI2917209T1/sl unknown
- 2013-11-11 AU AU2013343430A patent/AU2013343430B2/en active Active
- 2013-11-11 PT PT137948378T patent/PT2917209T/pt unknown
- 2013-11-11 MX MX2015005931A patent/MX367488B/es active IP Right Grant
- 2013-11-11 SM SM20170202T patent/SMT201700202T1/it unknown
- 2013-11-11 DK DK13794837.8T patent/DK2917209T3/en active
- 2013-11-11 ME MEP-2017-76A patent/ME02706B/me unknown
- 2013-11-11 EP EP13794837.8A patent/EP2917209B1/en active Active
- 2013-11-11 CN CN201380059126.XA patent/CN104903314B/zh active Active
- 2013-11-11 RS RS20170362A patent/RS55865B1/sr unknown
- 2013-11-11 NZ NZ709096A patent/NZ709096A/en unknown
- 2013-11-11 HR HRP20170485TT patent/HRP20170485T1/hr unknown
- 2013-11-11 CA CA2890042A patent/CA2890042C/en active Active
- 2013-11-11 KR KR1020157015736A patent/KR102151290B1/ko active Active
- 2013-11-11 ES ES13794837.8T patent/ES2621672T3/es active Active
- 2013-11-11 HU HUE13794837A patent/HUE032472T2/en unknown
- 2013-11-11 LT LTEP13794837.8T patent/LT2917209T/lt unknown
- 2013-11-11 BR BR112015010377A patent/BR112015010377A8/pt not_active Application Discontinuation
- 2013-11-11 WO PCT/EP2013/073460 patent/WO2014072498A1/en not_active Ceased
- 2013-11-11 PL PL13794837T patent/PL2917209T3/pl unknown
- 2013-11-11 EA EA201590942A patent/EA028422B1/ru not_active IP Right Cessation
- 2013-11-11 JP JP2015541169A patent/JP6203278B2/ja active Active
- 2013-11-11 US US14/436,715 patent/US10125097B2/en active Active
-
2015
- 2015-06-12 ZA ZA2015/04269A patent/ZA201504269B/en unknown
-
2017
- 2017-04-06 CY CY20171100410T patent/CY1118818T1/el unknown
-
2018
- 2018-09-26 US US16/142,907 patent/US10611727B2/en active Active
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