DK2917209T3 - 1-[1-Benzoyl)-pyrrolidin-2-carbonyl]-pyrrolidin-2-carbonitrilderivater - Google Patents
1-[1-Benzoyl)-pyrrolidin-2-carbonyl]-pyrrolidin-2-carbonitrilderivater Download PDFInfo
- Publication number
- DK2917209T3 DK2917209T3 DK13794837.8T DK13794837T DK2917209T3 DK 2917209 T3 DK2917209 T3 DK 2917209T3 DK 13794837 T DK13794837 T DK 13794837T DK 2917209 T3 DK2917209 T3 DK 2917209T3
- Authority
- DK
- Denmark
- Prior art keywords
- pyrrolidine
- carbonyl
- formula
- carbonitrile
- compound
- Prior art date
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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)
- Public Health (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (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)
Claims (13)
1. Forbindelse med formlen (I)
hvor R1; R2, R3 og R4 uafhængigt er valgt fra gruppen bestående af Ci^alkoxy, C-m. alkylcarbonyloxy, benzyloxy, phenylcarbonyloxy, naphthylcarbonyloxy, quinoli-nylcarbonyloxy, isoquinolinylcarbonyloxy, trifluormethyl, halogen og hydrogen; R5 er valgt fra gruppen bestående af halogen, nitril, Ci^alkoxy, C^alkylthio, Ci_4alkyl, phenyl, phenoxy, phenylthio og trifluormethyl; R6 er valgt fra gruppen bestående af hydrogen, fluor og methyl; eller et farmaceutisk acceptabelt salt, enantiomer, diastereomer, geometrisk isomer eller solvat deraf.
2. Forbindelse ifølge krav 1, hvor R2 og R4 uafhængigt er valgt fra gruppen bestående af hydrogen, halogen, trifluormethyl og Ci^alkoxy
3. Forbindelse ifølge krav 2, hvor R2 er valgt fra gruppen bestående af hydrogen og methoxy, og R4 er valgt fra gruppen bestående af fluor, trifluormethyl og methoxy.
4. Forbindelse ifølge et hvilket som helst af kravene 1 til 3, hvor R3 er benzyloxy.
5. Forbindelse ifølge et hvilket som helst af kravene 1 til 4, hvor R5 er fluor.
6. Forbindelse ifølge et hvilket som helst af kravene 1 til 5, hvor R6 er hydrogen eller fluor.
7. Forbindelse ifølge krav 1, hvor forbindelsen er valgt blandt: • (S)-1-((2S,4R)-1-(4-(benzyloxy)-3,5-dimethoxybenzoyl)-4-methoxypyrrolidin-2-carbonyl)pyrrolidin-2-ca rbonitril • (S)-1-((2S,4R)-1-(4-(benzyloxy)-3,5-dimethoxybenzoyl)-4-fluorpyrrolidin-2-carbonyl)pyrrolidin-2-ca rbonitril • (S)-1-((2S,4S)-1-(4-(benzyloxy)-3,5-dimethoxybenzoyl)-4-phenylpyrrolidin-2-carbonyl)pyrrolidin-2-ca rbonitril • (S)-1 -((2S)-1 -(4-(benzyloxy)-3,5-dimethoxybenzoyl)-4,4-difluorpyrrolidin-2-carbonyl)pyrrolidin-2-ca rbonitril • (S)-1-((2S,4S)-1-(4-(benzyloxy)-3,5-dimethoxybenzoyl)-4-(methylthio)pyrro-lidin-2-carbonyl)pyrrolidin-2-ca rbonitril • (S)-1-((2S,4S)-1-(4-(benzyloxy)-3,5-dimethoxybenzoyl)-4-methylpyrrolidin-2-carbonyl)pyrrolidin-2-ca rbonitril • (S)-1-((2S,4R)-1-(4-(benzyloxy)-3,5-dimethoxybenzoyl)-4-cyanopyrrolidin-2-carbonyl)pyrrolidin-2-ca rbonitril • (S)-1-((2S,4S)-1-(4-(benzyloxy)-3,5-dimethoxybenzoyl)-4-(trifluormethyl)-pyrrolidin-2-carbonyl)pyrrolidin-2-ca rbonitril • (S)-1-((2S,4R)-1-(4-(benzyloxy)-3,5-dimethoxybenzoyl)-4-(tert-butoxy) pyrroli-din-2-carbonyl)pyrrolidin-2-ca rbonitril • (S)-1-((2S,4R)-1-(4-(benzyloxy)-3,5-dimethoxybenzoyl)-4-acetoxypyrrolidin-2-carbonyl)pyrrolidin-2-ca rbonitril • (S)-1 -((2S)-1 -(4-acetoxy-3,5-dimethoxybenzoyl)-4,4-difluorpyrrolidin-2-carbonyl)pyrrolidin-2-ca rbonitril • (S)-1 -((2S)-1 -(4-benzoyloxy-3,5-dimethoxybenzoyl)-4,4-difluorpyrrolidin-2-carbonyl)pyrrolidin-2-carbonitril • (S)-1 -((2S)-1 -(3,4-dibenzyloxy-5-methoxybenzoyl)-4,4-difluorpyrrolidin-2-carbonyl)pyrrolidin-2-ca rbonitril • (S)-1 -((2S)-1 -(3,4-dibenzoyloxy-5-methoxybenzoyl)-4,4-difluorpyrrolidin-2-carbonyl)pyrrolidin-2-ca rbonitril • (S)-1 -((2S)-1 -(3-acetoxy-4,5-dimethoxybenzoyl)-4,4-difluorpyrrolidin-2-carbonyl)pyrrolidin-2-ca rbonitril • (S)-1 -((2S)-1 -(3-pivaloyloxy-4,5-dimethoxybenzoyl)-4,4-difluorpyrrolidin-2-carbonyl)pyrrolidin-2-ca rbonitril • (S)-1 -((S)-1 -(4-(benzyloxy)benzoyl)-4,4-difluorpyrrolidin-2-carbonyl)pyrrolidin-2-carbonitril • (S)-1 -((S)-1 -(3-(benzyloxy)benzoyl)-4,4-difluorpyrrolidin-2-carbonyl)pyrrolidin-2-carbonitril • (S)-1 -((S)-1 -(2-(benzyloxy)benzoyl)-4,4-difluorpyrrolidin-2-carbonyl)pyrrolidin-2-carbonitril • (S)-1 -((S)-1 -(4-(benzyloxy)-3-(trifluormethyl)benzoyl)-4,4-difluorpyrrolidin-2-carbonyl)pyrrolidin-2-ca rbonitril • (S)-1 -((S)-1 -(4-(benzyloxy)-3-fluorbenzoyl)-4,4-difluorpyrrolidin-2-carbonyl)-pyrrolidin-2-ca rbonitril ler et farmaceutisk acceptabelt salt, enantiomer, diastereomer, geometrisk isomer ler solvat deraf.
Fremgangsmåde til fremstilling af en forbindelse med formlen (I) som defineret i et rilket som helst af kravene 1 til 7 eller et farmaceutisk acceptabelt salt, enantiomer, astereomer, geometrisk isomer eller solvat deraf, hvilken fremgangsmåde omfatter a) omsætning af en forbindelse med formlen (IX):
hvor R1, R2, R3, R4, R5 og R6 er som defineret ovenfor i formel (I), med en forbindelse med formlen (XI):
hvilket giver en
forbindelse med formlen (XII); b) hydrolysering af forbindelsen med formlen (XII), hvilket giver forbindelsen med formlen (XIV)
c) udsættelse af forbindelsen med formlen (XIV) for betingelser, der er i stand til at omdanne en carboxamidgruppe til en nitrilgruppe, hvilket giver forbindelsen med formlen (I); hvor trin b) og c) kan udføres separat eller i en one pot-reaktion.
9. Fremgangsmåde til fremstilling af en forbindelse med formlen (I) som defineret i et hvilket som helst af kravene 1 til 7 eller et farmaceutisk acceptabelt salt, enantiomer, diastereomer, geometrisk isomer eller solvat deraf, hvilken fremgangsmåde omfatter omsætning af en forbindelse med formlen (IX):
hvor R1, R2, R3, R4, R5 og R6 er som defineret ovenfor i formel (I), med en forbindelse med formlen (IV)
10. Farmaceutisk præparat, som omfatter mindst én forbindelse med formlen (I) som defineret i et hvilket som helst af kravene 1 til 7 eller et farmaceutisk acceptabelt salt, enantiomer, diastereomer, geometrisk isomer eller solvat deraf og en farmaceutisk acceptabel bærer, adjuvans eller vehikel.
11. Forbindelse med formlen (I) som defineret i et hvilket som helst af kravene 1 til 7 til anvendelse som lægemiddel.
12. Forbindelse med formlen (I) som defineret i et hvilket som helst af kravene 1 til 7 til anvendelse til behandling og/eller profylakse af en kognitiv lidelse.
13. Forbindelse til anvendelse som defineret i krav 12, hvor den kognitive lidelse er en kognitiv lidelse, som er forbundet med en sygdom, der er valgt fra gruppen bestående af skizofreni, bipolær affektiv lidelse, Alzheimers sygdom og Parkinsons sygdom.
Applications Claiming Priority (2)
| 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 |
| 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 |
|---|---|
| DK2917209T3 true DK2917209T3 (da) | 2017-04-18 |
Family
ID=47278735
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK13794837.8T DK2917209T3 (da) | 2012-11-12 | 2013-11-11 | 1-[1-Benzoyl)-pyrrolidin-2-carbonyl]-pyrrolidin-2-carbonitrilderivater |
Country Status (25)
| Country | Link |
|---|---|
| US (2) | US10125097B2 (da) |
| EP (2) | EP2730571A1 (da) |
| JP (1) | JP6203278B2 (da) |
| KR (1) | KR102151290B1 (da) |
| CN (1) | CN104903314B (da) |
| AU (1) | AU2013343430B2 (da) |
| BR (1) | BR112015010377A8 (da) |
| CA (1) | CA2890042C (da) |
| CY (1) | CY1118818T1 (da) |
| DK (1) | DK2917209T3 (da) |
| EA (1) | EA028422B1 (da) |
| ES (1) | ES2621672T3 (da) |
| HK (1) | HK1214597A1 (da) |
| HR (1) | HRP20170485T1 (da) |
| HU (1) | HUE032472T2 (da) |
| LT (1) | LT2917209T (da) |
| ME (1) | ME02706B (da) |
| MX (1) | MX367488B (da) |
| NZ (1) | NZ709096A (da) |
| PL (1) | PL2917209T3 (da) |
| PT (1) | PT2917209T (da) |
| RS (1) | RS55865B1 (da) |
| SI (1) | SI2917209T1 (da) |
| WO (1) | WO2014072498A1 (da) |
| ZA (1) | ZA201504269B (da) |
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 |
| JP2021506972A (ja) | 2017-12-15 | 2021-02-22 | プラクシス バイオテック エルエルシー | 線維芽細胞活性化タンパク質の阻害剤 |
| WO2020132661A2 (en) | 2018-12-21 | 2020-06-25 | Praxis Biotech LLC | Inhibitors of fibroblast activation protein |
| CN117545738A (zh) | 2020-07-07 | 2024-02-09 | 安克瑞治疗公司 | 1-[1-(4-苄氧基-3,5-二氟-苯甲酰基)-4-氟-吡咯烷-2-羰基]吡咯烷-2-腈 |
| CN117062824A (zh) * | 2020-12-28 | 2023-11-14 | 砂拉越生物多元化中心 | 治疗神经退行性疾病的化合物及其分离方法 |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2511605B2 (ja) * | 1990-06-04 | 1996-07-03 | ファイザー・インコーポレーテッド | 芳香性ピロリジンおよびチアゾリヂンアミド類 |
| 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 |
| CN1620433A (zh) * | 2000-07-19 | 2005-05-25 | 霍夫曼-拉罗奇有限公司 | 作为内皮肽转化酶抑制剂的吡咯烷衍生物 |
| 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 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 RS RS20170362A patent/RS55865B1/sr unknown
- 2013-11-11 US US14/436,715 patent/US10125097B2/en active Active
- 2013-11-11 HU HUE13794837A patent/HUE032472T2/en unknown
- 2013-11-11 ES ES13794837.8T patent/ES2621672T3/es active Active
- 2013-11-11 WO PCT/EP2013/073460 patent/WO2014072498A1/en active Application Filing
- 2013-11-11 SI SI201330601A patent/SI2917209T1/sl unknown
- 2013-11-11 AU AU2013343430A patent/AU2013343430B2/en active Active
- 2013-11-11 MX MX2015005931A patent/MX367488B/es active IP Right Grant
- 2013-11-11 EA EA201590942A patent/EA028422B1/ru not_active IP Right Cessation
- 2013-11-11 KR KR1020157015736A patent/KR102151290B1/ko active IP Right Grant
- 2013-11-11 BR BR112015010377A patent/BR112015010377A8/pt not_active Application Discontinuation
- 2013-11-11 PL PL13794837T patent/PL2917209T3/pl unknown
- 2013-11-11 NZ NZ709096A patent/NZ709096A/en unknown
- 2013-11-11 DK DK13794837.8T patent/DK2917209T3/da active
- 2013-11-11 LT LTEP13794837.8T patent/LT2917209T/lt unknown
- 2013-11-11 CN CN201380059126.XA patent/CN104903314B/zh active Active
- 2013-11-11 PT PT137948378T patent/PT2917209T/pt unknown
- 2013-11-11 CA CA2890042A patent/CA2890042C/en active Active
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2015
- 2015-06-12 ZA ZA2015/04269A patent/ZA201504269B/en unknown
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2016
- 2016-03-07 HK HK16102568.0A patent/HK1214597A1/zh unknown
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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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