EA031353B1 - Кристаллический о-метилоксим (3z,5s)-5-(гидроксиметил)-1-[(2'-метил-1,1'-бифенил-4-ил)карбонил]пирролидин-3-он, полезный в способах лечения состояний, связанных с активностью ot-r - Google Patents
Кристаллический о-метилоксим (3z,5s)-5-(гидроксиметил)-1-[(2'-метил-1,1'-бифенил-4-ил)карбонил]пирролидин-3-он, полезный в способах лечения состояний, связанных с активностью ot-r Download PDFInfo
- Publication number
- EA031353B1 EA031353B1 EA201790080A EA201790080A EA031353B1 EA 031353 B1 EA031353 B1 EA 031353B1 EA 201790080 A EA201790080 A EA 201790080A EA 201790080 A EA201790080 A EA 201790080A EA 031353 B1 EA031353 B1 EA 031353B1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- carbonyl
- methyl
- biphenyl
- hydroxymethyl
- methyloxime
- Prior art date
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Classifications
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
-
- 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
- C07D207/18—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 one double bond between ring members or between a ring member and a non-ring member
- C07D207/22—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 one double bond between ring members or between a ring member and a non-ring member 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/08—Drugs for disorders of the urinary system of the prostate
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/04—Drugs for genital or sexual disorders; Contraceptives for inducing labour or abortion; Uterotonics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/06—Antiabortive agents; Labour repressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
-
- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/10—Drugs for disorders of the endocrine system of the posterior pituitary hormones, e.g. oxytocin, ADH
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
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- Endocrinology (AREA)
- Reproductive Health (AREA)
- Epidemiology (AREA)
- Gynecology & Obstetrics (AREA)
- Pregnancy & Childbirth (AREA)
- Diabetes (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Psychiatry (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyrrole Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201462020076P | 2014-07-02 | 2014-07-02 | |
| PCT/EP2015/062881 WO2016000920A1 (en) | 2014-07-02 | 2015-06-10 | Crystalline (3z,5s)-5-(hydroxymethyl)-1-[(2'-methyl-1,1'-biphenyl-4-yl)carbonyl]pyrrolidin-3-one o-methyloxime useful in methods of treating conditions related to the ot-r activity |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EA201790080A1 EA201790080A1 (ru) | 2017-06-30 |
| EA031353B1 true EA031353B1 (ru) | 2018-12-28 |
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Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
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| EA201790080A EA031353B1 (ru) | 2014-07-02 | 2015-06-10 | Кристаллический о-метилоксим (3z,5s)-5-(гидроксиметил)-1-[(2'-метил-1,1'-бифенил-4-ил)карбонил]пирролидин-3-он, полезный в способах лечения состояний, связанных с активностью ot-r |
| EA201891873A EA201891873A1 (ru) | 2014-07-02 | 2015-06-10 | Кристаллический о-метилоксим (3z,5s)-5-(гидроксиметил)-1-[(2'-метил-1,1'-бифенил-4-ил)карбонил]пирролидин-3-он, полезный в способах лечения состояний, связанных с активностью ot-r |
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| Application Number | Title | Priority Date | Filing Date |
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| EA201891873A EA201891873A1 (ru) | 2014-07-02 | 2015-06-10 | Кристаллический о-метилоксим (3z,5s)-5-(гидроксиметил)-1-[(2'-метил-1,1'-бифенил-4-ил)карбонил]пирролидин-3-он, полезный в способах лечения состояний, связанных с активностью ot-r |
Country Status (13)
| Country | Link |
|---|---|
| US (2) | US9718772B2 (enExample) |
| EP (2) | EP3753921A1 (enExample) |
| JP (4) | JP2017519015A (enExample) |
| KR (1) | KR102470283B1 (enExample) |
| CN (3) | CN114105851A (enExample) |
| AU (1) | AU2015283133B2 (enExample) |
| CA (1) | CA2953722C (enExample) |
| EA (2) | EA031353B1 (enExample) |
| ES (1) | ES2774789T3 (enExample) |
| IL (1) | IL249652B (enExample) |
| MX (1) | MX371068B (enExample) |
| UA (1) | UA122210C2 (enExample) |
| WO (1) | WO2016000920A1 (enExample) |
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| EP2845850A1 (en) | 2013-09-10 | 2015-03-11 | ObsEva S.A. | Pyrrolidine derivatives as oxytocin/vasopressin V1a receptors antagonists |
| EP2886107A1 (en) | 2013-12-17 | 2015-06-24 | ObsEva S.A. | Oral formulations of pyrrolydine derivatives |
| EP3753921A1 (en) | 2014-07-02 | 2020-12-23 | ObsEva S.A. | Crystalline (3z,5s)-5-(hydroxymethyl)-1-[(2'-methyl-1,1'-biphenyl-4-yl)carbonyl]pyrrolidin-3-one o-methyloxime useful in methods of treating conditions related to the ot-r activity |
| ES2915948T3 (es) | 2016-01-04 | 2022-06-27 | ObsEva SA | Administración conjunta de alfa-aminoéster de derivado de hidroxipropiltiazolidin-carboxamida y un agente tocolítico |
| WO2018015497A2 (en) * | 2016-07-21 | 2018-01-25 | ObsEva S.A. | Oxytocin antagonist dosing regimens for promoting embryo implantation and preventing miscarriage |
| EP4025207A1 (en) * | 2019-09-03 | 2022-07-13 | ObsEva S.A. | Oxytocin antagonist dosing regimens for promoting embryo implantation and preventing miscarriage |
| JP7083793B2 (ja) * | 2019-09-10 | 2022-06-13 | Ｊｆｅケミカル株式会社 | パラターフェニルテトラカルボン酸およびパラターフェニルテトラカルボン酸二無水物の製造方法 |
| AU2021218895A1 (en) | 2020-02-10 | 2022-09-15 | ObsEva S.A. | Biomarkers for oxytocin receptor antagonist therapy |
| WO2022211810A1 (en) * | 2021-03-31 | 2022-10-06 | The Board Of Trustees Of The Leland Stanford Junior University | Formulations for prolonging gestation and for complications of menstruation or gestation |
| WO2026018221A1 (en) * | 2024-07-18 | 2026-01-22 | ReproNovo SA | Crystalline compositions for improving embryo implantation and methods of using the same |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004005249A1 (en) * | 2002-07-05 | 2004-01-15 | Applied Research Systems Ars Holding N.V. | Pyrrolidine derivatives as oxytocin antagonists |
| EP2845850A1 (en) * | 2013-09-10 | 2015-03-11 | ObsEva S.A. | Pyrrolidine derivatives as oxytocin/vasopressin V1a receptors antagonists |
| EP2886107A1 (en) * | 2013-12-17 | 2015-06-24 | ObsEva S.A. | Oral formulations of pyrrolydine derivatives |
Family Cites Families (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| YU120988A (en) | 1988-06-23 | 1990-06-30 | Lek Tovarna Farmacevtskih | Process for preparing new dispersion pills of cimetidine |
| YU183988A (en) | 1988-09-30 | 1990-08-31 | Lek Tovarna Farmacevtskih | Process for preparing dispersion pills of dihydroergotoxine |
| US5089043A (en) | 1989-11-09 | 1992-02-18 | Shionogi & Co., Ltd. | Heterocyclic oxy-phenoxyacetic acid derivatives and their use as herbicides |
| US5889001A (en) | 1993-07-29 | 1999-03-30 | American Cyanamid Company | Tricyclic diazepine vasopressin antagonists and oxytocin antagonists |
| JP3534903B2 (ja) | 1995-06-09 | 2004-06-07 | 鐘淵化学工業株式会社 | １−［３−クロロ−（２ｓ）−メチルプロピオニル］−ピロリジン−（２ｓ）−カルボン酸の製造方法 |
| GB9603699D0 (en) | 1996-02-21 | 1996-04-17 | Boots Co Plc | Therapeutic composition |
| US6696484B2 (en) | 1997-10-31 | 2004-02-24 | University Of Chicago Office Of Technology And Intellectual Property | Method and compositions for regulation of 5-alpha reductase activity |
| US6329418B1 (en) | 1998-04-14 | 2001-12-11 | The Procter & Gamble Company | Substituted pyrrolidine hydroxamate metalloprotease inhibitors |
| DE60027761T2 (de) | 1999-12-09 | 2007-01-25 | Reckitt Benckiser Healthcare (Uk) Ltd., Slough | Komprimierte zubereitung enthaltend nichtsteroidale entzündungshemmer |
| ES2261404T3 (es) | 2000-03-27 | 2006-11-16 | Applied Research Systems Ars Holding N.V. | Derivados de pirrolidina utiles como inhibidores de bax. |
| DK1268418T3 (da) | 2000-03-27 | 2006-09-25 | Applied Research Systems | Farmaceutisk aktive pyrrolidinderivater som Bax-inhibitorer |
| TW536751B (en) | 2000-07-14 | 2003-06-11 | Nitto Denko Corp | Cleaning sheet, conveying member using the same, and substrate processing equipment cleaning method using them |
| IL157995A0 (en) | 2001-03-20 | 2004-03-28 | Applied Research Systems | The use of pyrrolidine ester derivatives in modulation of oxytoxin activity, some new such derivatives, their preparation and pharmaceutical compositions containing them |
| KR200245627Y1 (ko) * | 2001-05-15 | 2001-10-15 | 김병두 | 전기 가열부재가 부착된 냄비 |
| EP1444225B1 (en) | 2001-06-18 | 2012-10-10 | Merck Serono SA | Pyrrolidine oxadiazole- and thiadiazole oxime derivatives being oxytocin receptor antagonists. |
| JP2003192582A (ja) | 2001-12-12 | 2003-07-09 | Merck Patent Gmbh | ナプロキセンナトリウムを含む速放性錠剤 |
| ES2333719T3 (es) | 2003-02-27 | 2010-02-26 | Merck Serono Sa | Derivados de pirrolidina en calidad de antagonistas de oxitocina. |
| EA011026B1 (ru) | 2004-02-26 | 2008-12-30 | Лаборатуар Сероно Са | Способ получения пирролидиноксимов |
| GB2411355B (en) | 2004-02-27 | 2006-02-22 | Niche Generics Ltd | Pharmaceutical composition |
| KR100985449B1 (ko) | 2005-05-10 | 2010-10-05 | 페링 인터내셔널 센터 에스 에이 | 옥시톡신 및/또는 바소프레신 길항제의 용도 |
| JP2008189732A (ja) | 2007-02-01 | 2008-08-21 | Fujifilm Corp | セルロースアシレート組成物、セルロースアシレートフィルム、光学補償シート、偏光板および液晶表示装置 |
| PT2572705T (pt) | 2007-10-01 | 2017-11-08 | Lesvi Laboratorios Sl | Comprimidos orodispersíveis |
| US9201077B2 (en) | 2009-07-27 | 2015-12-01 | Colorado State University Research Foundation | Direct enzyme immunoassay for measurement of serum progesterone levels |
| HK1213454A1 (zh) | 2012-11-26 | 2016-07-08 | Ferring B.V. | 使用图像分析诊断子宫收缩水平的方法和系统 |
| EP3753921A1 (en) | 2014-07-02 | 2020-12-23 | ObsEva S.A. | Crystalline (3z,5s)-5-(hydroxymethyl)-1-[(2'-methyl-1,1'-biphenyl-4-yl)carbonyl]pyrrolidin-3-one o-methyloxime useful in methods of treating conditions related to the ot-r activity |
| PL3037101T3 (pl) | 2014-12-22 | 2019-06-28 | Ferring B.V. | Terapia antagonistą receptora oksytocyny w fazie lutealnej w celu implantacji i uzyskania ciąży u kobiet poddawanych technikom wspomaganego rozrodu |
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2015
- 2015-06-10 EP EP19204954.2A patent/EP3753921A1/en active Pending
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- 2015-06-10 CN CN202111228955.9A patent/CN114105850A/zh active Pending
- 2015-06-10 CN CN201580047177.XA patent/CN106795110A/zh active Pending
- 2015-06-10 WO PCT/EP2015/062881 patent/WO2016000920A1/en not_active Ceased
- 2015-06-10 KR KR1020177001267A patent/KR102470283B1/ko active Active
- 2015-06-10 MX MX2016016751A patent/MX371068B/es active IP Right Grant
- 2015-06-10 ES ES15730094T patent/ES2774789T3/es active Active
- 2015-06-10 EP EP15730094.8A patent/EP3164384B1/en active Active
- 2015-06-10 JP JP2016573776A patent/JP2017519015A/ja active Pending
- 2015-06-10 EA EA201790080A patent/EA031353B1/ru unknown
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- 2015-06-10 EA EA201891873A patent/EA201891873A1/ru unknown
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2016
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2017
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2020
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2022
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004005249A1 (en) * | 2002-07-05 | 2004-01-15 | Applied Research Systems Ars Holding N.V. | Pyrrolidine derivatives as oxytocin antagonists |
| EP2845850A1 (en) * | 2013-09-10 | 2015-03-11 | ObsEva S.A. | Pyrrolidine derivatives as oxytocin/vasopressin V1a receptors antagonists |
| EP2886107A1 (en) * | 2013-12-17 | 2015-06-24 | ObsEva S.A. | Oral formulations of pyrrolydine derivatives |
Non-Patent Citations (1)
| Title |
|---|
| CAIRA: "Crystalline Polymorphism of Organic Compounds", TOPICS IN CURRENT CHEMISTRY., SPRINGER, BERLIN., DE, vol. 198, 1 January 1998 (1998-01-01), DE, pages 163 - 208, XP008166276, ISSN: 0340-1022 * |
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| CA2953722A1 (en) | 2016-01-07 |
| JP2021038236A (ja) | 2021-03-11 |
| US10752583B2 (en) | 2020-08-25 |
| EA201790080A1 (ru) | 2017-06-30 |
| MX2016016751A (es) | 2017-08-08 |
| JP2023018037A (ja) | 2023-02-07 |
| CA2953722C (en) | 2022-09-13 |
| JP2025013885A (ja) | 2025-01-28 |
| JP2017519015A (ja) | 2017-07-13 |
| IL249652A0 (en) | 2017-02-28 |
| AU2015283133A1 (en) | 2017-02-16 |
| ES2774789T3 (es) | 2020-07-22 |
| EA201891873A1 (ru) | 2019-04-30 |
| US20170320822A1 (en) | 2017-11-09 |
| US9718772B2 (en) | 2017-08-01 |
| KR102470283B1 (ko) | 2022-11-23 |
| EP3164384B1 (en) | 2019-12-04 |
| EP3164384A1 (en) | 2017-05-10 |
| CN114105851A (zh) | 2022-03-01 |
| CN106795110A (zh) | 2017-05-31 |
| MX371068B (es) | 2020-01-15 |
| UA122210C2 (uk) | 2020-10-12 |
| KR20170023961A (ko) | 2017-03-06 |
| AU2015283133B2 (en) | 2019-05-16 |
| WO2016000920A1 (en) | 2016-01-07 |
| EP3753921A1 (en) | 2020-12-23 |
| CN114105850A (zh) | 2022-03-01 |
| IL249652B (en) | 2021-09-30 |
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