HRP20170485T1 - Derivati 1-[1-(benzoil)pirolidin-2-karbonil]pirolidin-2-karbonitrila - Google Patents
Derivati 1-[1-(benzoil)pirolidin-2-karbonil]pirolidin-2-karbonitrila Download PDFInfo
- Publication number
- HRP20170485T1 HRP20170485T1 HRP20170485TT HRP20170485T HRP20170485T1 HR P20170485 T1 HRP20170485 T1 HR P20170485T1 HR P20170485T T HRP20170485T T HR P20170485TT HR P20170485 T HRP20170485 T HR P20170485T HR P20170485 T1 HRP20170485 T1 HR P20170485T1
- Authority
- HR
- Croatia
- Prior art keywords
- pyrrolidine
- carbonyl
- carbonitrile
- compound
- benzyloxy
- Prior art date
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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 1
- 150000001875 compounds Chemical class 0.000 claims 23
- 229910052739 hydrogen Inorganic materials 0.000 claims 5
- 239000001257 hydrogen Substances 0.000 claims 5
- 150000003839 salts Chemical class 0.000 claims 5
- 239000012453 solvate Substances 0.000 claims 5
- 238000006243 chemical reaction Methods 0.000 claims 4
- 229910052731 fluorine Inorganic materials 0.000 claims 4
- 239000011737 fluorine Substances 0.000 claims 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 4
- 208000010877 cognitive disease Diseases 0.000 claims 3
- 229910052736 halogen Inorganic materials 0.000 claims 3
- 150000002367 halogens Chemical class 0.000 claims 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims 2
- 125000003545 alkoxy group Chemical group 0.000 claims 2
- -1 benzyloxy, phenylcarbonyloxy, naphthylcarbonyloxy, quinolinylcarbonyloxy, isoquinolinylcarbonyloxy Chemical group 0.000 claims 2
- 125000001153 fluoro group Chemical group F* 0.000 claims 2
- 150000002431 hydrogen Chemical class 0.000 claims 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 2
- 238000000034 method Methods 0.000 claims 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 2
- 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 1
- 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 1
- 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 1
- 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 1
- 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 1
- 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 1
- 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 1
- 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 1
- 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 1
- 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 1
- 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 1
- 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 1
- AXAQGOMOKDBQGF-FKBYEOEOSA-N (2s)-1-[(2s,4s)-1-(3,5-dimethoxy-4-phenylmethoxybenzoyl)-4-methylsulfanylpyrrolidine-2-carbonyl]pyrrolidine-2-carbonitrile Chemical compound COC1=CC(C(=O)N2[C@@H](C[C@@H](C2)SC)C(=O)N2[C@@H](CCC2)C#N)=CC(OC)=C1OCC1=CC=CC=C1 AXAQGOMOKDBQGF-FKBYEOEOSA-N 0.000 claims 1
- 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 1
- 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 1
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims 1
- 208000017194 Affective disease Diseases 0.000 claims 1
- 208000024827 Alzheimer disease Diseases 0.000 claims 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 1
- 208000019022 Mood disease Diseases 0.000 claims 1
- 208000018737 Parkinson disease Diseases 0.000 claims 1
- 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 1
- 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 1
- 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 1
- 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 1
- 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 1
- 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 1
- 239000002671 adjuvant Substances 0.000 claims 1
- 125000005196 alkyl carbonyloxy group Chemical group 0.000 claims 1
- 125000000217 alkyl group Chemical group 0.000 claims 1
- 125000004414 alkyl thio group Chemical group 0.000 claims 1
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims 1
- 125000005392 carboxamide group Chemical group NC(=O)* 0.000 claims 1
- 201000010099 disease Diseases 0.000 claims 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 229940079593 drug Drugs 0.000 claims 1
- 230000007062 hydrolysis Effects 0.000 claims 1
- 238000006460 hydrolysis reaction Methods 0.000 claims 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 1
- 125000002560 nitrile group Chemical group 0.000 claims 1
- 150000002825 nitriles Chemical class 0.000 claims 1
- 239000000825 pharmaceutical preparation Substances 0.000 claims 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 1
- 238000011321 prophylaxis Methods 0.000 claims 1
- 201000000980 schizophrenia Diseases 0.000 claims 1
- 238000011282 treatment Methods 0.000 claims 1
Classifications
-
- 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
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Psychiatry (AREA)
- Psychology (AREA)
- Hospice & Palliative Care (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyrrole Compounds (AREA)
- Epidemiology (AREA)
Claims (13)
1. Spoj formule (I)
[image]
,
naznačen time što
R1, R2, R3 i R4 se neovisno bira iz skupine koju čine C1-4alkoksi, C1-4alkilkarboniloksi, benziloksi, fenilkarboniloksi, naftilkarboniloksi, kinolinilkarboniloksi, izokinolinilkarboniloksi, trifluormetil, halogen i vodik;
R5 se bira iz skupine koju čine halogen, nitril, C1-4alkoksi, C1-4alkiltio, C1-4alkil, fenil, fenoksi, feniltio i trifluormetil;
R6 se bira iz skupine koju čine vodik, fluor i metil;
ili njegova farmaceutski prihvatljiva sol, enantiomer, dijastereomer, geometrijski izomer ili solvat.
2. Spoj u skladu s patentnim zahtjevom 1 naznačen time što se R2 i R4 neovisno bira iz skupine koju čine vodik, halogen, trifluormetil i C1-4alkoksi.
3. Spoj u skladu s patentnim zahtjevom 2, naznačen time što se R2 bira iz skupine koju čine vodik i metoksi, a R4 se bira iz skupine koju čine fluor, trifluormetil i metoksi.
4. Spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 3, naznačen time što je R3 benziloksi.
5. Spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 4, naznačen time što je R5 fluor.
6. Spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 5, naznačen time što je R6 vodik ili fluor.
7. Spoj u skladu s patentnim zahtjevom 1, naznačen time što se navedeni spoj bira između:
• (S)-1-((2S,4R)-1-(4-(benziloksi)-3,5-dimetoksibenzoil)-4-metoksipirolidin-2-karbonil)pirolidin-2-karbonitrila
• (S)-1-((2S,4R)-1-(4-(benziloksi)-3,5-dimetoksibenzoil)-4-fluorpirolidin-2-karbonil)pirolidin-2-karbonitrila
• (S)-1-((2S,4S)-1-(4-(benziloksi)-3,5-dimetoksibenzoil)-4-fenilpirolidin-2-karbonil)pirolidin-2-karbonitrila
• (S)-1-((2S)-1-(4-(benziloksi)-3,5-dimetoksibenzoil)-4,4-difluorpirolidin-2-karbonil)pirolidin-2-karbonitrila
• (S)-1-((2S,4S)-1-(4-(benziloksi)-3,5-dimetoksibenzoil)-4-(metiltio)pirolidin-2-karbonil)pirolidin-2-karbonitrila
• (S)-1-((2S,4S)-1-(4-(benziloksi)-3,5-dimetoksibenzoil)-4-metilpirolidin-2-karbonil)pirolidin-2-karbonitrila
• (S)-1-((2S,4R)-1-(4-(benziloksi)-3,5-dimetoksibenzoil)-4-cijanopirolidin-2-karbonil)pirolidin-2-karbonitrila
• (S)-1-((2S,4S)-1-(4-(benziloksi)-3,5-dimetoksibenzoil)-4-(trifluormetil)pirolidin-2-karbonil)pirolidin-2-karbonitrila
• (S)-1-((2S,4R)-1-(4-(benziloksi)-3,5-dimetoksibenzoil)-4-(tert-butoksi)pirolidin-2-karbonil)pirolidin-2-karbonitrila
• (S)-1-((2S,4R)-1-(4-(benziloksi)-3,5-dimetoksibenzoil)-4-acetoksipirolidin-2-karbonil)pirolidin-2-karbonitrila
• (S)-1-((2S)-1-(4-acetoksi-3,5-dimetoksibenzoil)-4,4-difluorpirolidin-2-karbonil)pirolidin-2-karbonitrila
• (S)-1-((2S)-1-(4-benzoiloksi-3,5-dimetoksibenzoil)-4,4-difluorpirolidin-2-karbonil)pirolidin-2-karbonitrila
• (S)-1-((2S)-1-(3,4-dibenziloksi-5-metoksibenzoil)-4,4-difluorpirolidin-2-karbonil)pirolidin-2-karbonitrila
• (S)-1-((2S)-1-(3,4-dibenzoiloksi-5-metoksibenzoil)-4,4-difluorpirolidin-2-karbonil)pirolidin-2-karbonitrila
• (S)-1-((2S)-1-(3-acetoksi-4,5-dimetoksibenzoil)-4,4-difluorpirolidin-2-karbonil)pirolidin-2-karbonitrila
• (S)-1-((2S)-1-(3-pivaloiloksi-4,5-dimetoksibenzoil)-4,4-difluorpirolidin-2-karbonil)pirolidin-2-karbonitrila
• (S)-1-((S)-1-(4-(benziloksi)benzoil)-4,4-difluorpirolidin-2-karbonil)pirolidin-2-karbonitrila
• (S)-1-((S)-1-(3-(benziloksi)benzoil)-4,4-difluorpirolidin-2-karbonil)pirolidin-2-karbonitrila
• (S)-1-((S)-1-(2-(benziloksi)benzoil)-4,4-difluorpirolidin-2-karbonil)pirolidin-2-karbonitrila
• (S)-1-((S)-1-(4-(benziloksi)-3-(trifluormetil)benzoil)-4,4-difluorpirolidin-2-karbonil)pirolidin-2-karbonitrila
• (S)-1-((S)-1-(4-(benziloksi)-3-fluorbenzoil)-4,4-difluorpirolidin-2-karbonil)pirolidin-2-karbonitrila
ili njihovih farmaceutski prihvatljivih soli, enantiomera, dijastereomera, geometrijskih izomera ili solvata.
8. Postupak dobivanja spoja formule (I) u skladu s bilo kojim od patentnih zahtjeva 1 do 7, ili njegove farmaceutski prihvatljive soli, enantiomera, dijastereomera, geometrijskog izomera ili solvata, naznačen time što se sastoji u
a) reakciji spoja formule (IX):
[image]
,
u kojoj su R1, R2, R3, R4, R5 i R6 definirani kao gore, u formuli (I), sa spojem formule (XI):
[image]
,
kako bi se dobilo spoj formule (XII):
[image]
;
b) hidrolizi spoja formule (XII) kako bi se dobilo spoj formule (XIV)
[image]
i
c) podvrgavanju spoja formule (XIV) uvjetima koji omogućuju pretvorbu karboksamidne skupine u nitrilnu skupinu, kako bi se dobilo spoj formule (I);
gdje se koraci b) i c) mogu provesti odvojeno ili reakcijom u jednoj posudi.
9. Postupak dobivanja spoja formule (I) u skladu s bilo kojim od patentnih zahtjeva 1 do 7, ili njegove farmaceutski prihvatljive soli, enantiomera, dijastereomera, geometrijskog izomera ili solvata, naznačen time što se sastoji u reakciji spoja formule (IX):
[image]
,
u kojoj su R1, R2, R3, R4, R5 i R6 definirani kao gore, u formuli (I), sa spojem formule (IV)
[image]
.
10. Farmaceutski pripravak, naznačen time što sadrži najmanje jedan spoj formule (I) u skladu s bilo kojim od patentnih zahtjeva 1 do 7, ili njegovu farmaceutski prihvatljivu sol, enantiomer, dijastereomer, geometrijski izomer ili solvat, kao i farmaceutski prihvatljivu podlogu, adjuvans ili vehikulum.
11. Spoj formule (I) u skladu s bilo kojim od patentnih zahtjeva 1 do 7, naznačen time što je namijenjen upotrebi kao medikament.
12. Spoj formule (I) u skladu s bilo kojim od patentnih zahtjeva 1 do 7, naznačen time što je namijenjen upotrebi u liječenju i/ili profilaksi kognitivnog poremećaja.
13. Spoj namijenjen upotrebi u skladu s patentnim zahtjevom 12, naznačen time što je kognitivni poremećaj kognitivni poremećaj povezan s bolešću koju se bira iz skupine koju čine shizofrenija, bipolarni afektivni poremećaj, Alzheimerova bolest i Parkinsonova bolest.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP12382446.8A EP2730571A1 (en) | 2012-11-12 | 2012-11-12 | 1-[1-(benzoyl)-pyrrolidine-2-carbonyl]-pyrrolidine-2-carbonitrile derivatives |
| EP13794837.8A EP2917209B1 (en) | 2012-11-12 | 2013-11-11 | 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 |
|---|---|
| HRP20170485T1 true HRP20170485T1 (hr) | 2017-06-02 |
Family
ID=47278735
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HRP20170485TT HRP20170485T1 (hr) | 2012-11-12 | 2017-03-22 | Derivati 1-[1-(benzoil)pirolidin-2-karbonil]pirolidin-2-karbonitrila |
Country Status (25)
| Country | Link |
|---|---|
| US (2) | US10125097B2 (hr) |
| EP (2) | EP2730571A1 (hr) |
| JP (1) | JP6203278B2 (hr) |
| KR (1) | KR102151290B1 (hr) |
| CN (1) | CN104903314B (hr) |
| AU (1) | AU2013343430B2 (hr) |
| BR (1) | BR112015010377A8 (hr) |
| CA (1) | CA2890042C (hr) |
| CY (1) | CY1118818T1 (hr) |
| DK (1) | DK2917209T3 (hr) |
| EA (1) | EA028422B1 (hr) |
| ES (1) | ES2621672T3 (hr) |
| HK (1) | HK1214597A1 (hr) |
| HR (1) | HRP20170485T1 (hr) |
| HU (1) | HUE032472T2 (hr) |
| LT (1) | LT2917209T (hr) |
| ME (1) | ME02706B (hr) |
| MX (1) | MX367488B (hr) |
| NZ (1) | NZ709096A (hr) |
| PL (1) | PL2917209T3 (hr) |
| PT (1) | PT2917209T (hr) |
| RS (1) | RS55865B1 (hr) |
| SI (1) | SI2917209T1 (hr) |
| WO (1) | WO2014072498A1 (hr) |
| ZA (1) | ZA201504269B (hr) |
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 |
| MX2020006128A (es) | 2017-12-15 | 2020-09-21 | Praxis Biotech LLC | Inhibidores de la proteina de activacion de fibroblastos. |
| WO2020132661A2 (en) | 2018-12-21 | 2020-06-25 | Praxis Biotech LLC | Inhibitors of fibroblast activation protein |
| WO2022008477A1 (en) | 2020-07-07 | 2022-01-13 | Accure Therapeutics, S.L. | 1-[1-(4-benzyloxy-3,5-difluoro-benzoyl)-4-fluoro-pyrrolidine-2-carbonyl]-pyrrolidine-2-carbonitrile |
| EP4271694A1 (en) * | 2020-12-28 | 2023-11-08 | 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 |
| AU2001270627A1 (en) * | 2000-07-19 | 2002-01-30 | F. Hoffmann-La Roche Ag | Pyrrolidine derivatives as inhibitors of endothelin-converting enzyme |
| 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 |
| WO2005027934A1 (ja) | 2003-09-24 | 2005-03-31 | Nippon Kayaku Kabushiki Kaisha | 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. |
| WO2010083570A1 (en) * | 2009-01-23 | 2010-07-29 | The University Of Sydney | 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 HU HUE13794837A patent/HUE032472T2/en unknown
- 2013-11-11 NZ NZ709096A patent/NZ709096A/en unknown
- 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 JP JP2015541169A patent/JP6203278B2/ja active Active
- 2013-11-11 KR KR1020157015736A patent/KR102151290B1/ko active IP Right Grant
- 2013-11-11 CN CN201380059126.XA patent/CN104903314B/zh active Active
- 2013-11-11 US US14/436,715 patent/US10125097B2/en active Active
- 2013-11-11 PT PT137948378T patent/PT2917209T/pt unknown
- 2013-11-11 WO PCT/EP2013/073460 patent/WO2014072498A1/en active Application Filing
- 2013-11-11 CA CA2890042A patent/CA2890042C/en active Active
- 2013-11-11 DK DK13794837.8T patent/DK2917209T3/en active
- 2013-11-11 PL PL13794837T patent/PL2917209T3/pl unknown
- 2013-11-11 BR BR112015010377A patent/BR112015010377A8/pt not_active Application Discontinuation
- 2013-11-11 EA EA201590942A patent/EA028422B1/ru not_active IP Right Cessation
- 2013-11-11 MX MX2015005931A patent/MX367488B/es active IP Right Grant
- 2013-11-11 RS RS20170362A patent/RS55865B1/sr unknown
- 2013-11-11 SI SI201330601A patent/SI2917209T1/sl unknown
- 2013-11-11 AU AU2013343430A patent/AU2013343430B2/en active Active
- 2013-11-11 ES ES13794837.8T patent/ES2621672T3/es active Active
- 2013-11-11 LT LTEP13794837.8T patent/LT2917209T/lt unknown
-
2015
- 2015-06-12 ZA ZA2015/04269A patent/ZA201504269B/en unknown
-
2016
- 2016-03-07 HK HK16102568.0A patent/HK1214597A1/zh unknown
-
2017
- 2017-03-22 HR HRP20170485TT patent/HRP20170485T1/hr unknown
- 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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