EA012115B1 - Кристаллическая форма хинолинон-карбоксамидного соединения - Google Patents
Кристаллическая форма хинолинон-карбоксамидного соединения Download PDFInfo
- Publication number
- EA012115B1 EA012115B1 EA200702161A EA200702161A EA012115B1 EA 012115 B1 EA012115 B1 EA 012115B1 EA 200702161 A EA200702161 A EA 200702161A EA 200702161 A EA200702161 A EA 200702161A EA 012115 B1 EA012115 B1 EA 012115B1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- crystalline
- salt form
- crystalline salt
- azabicyclo
- oxo
- Prior art date
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/46—8-Azabicyclo [3.2.1] octane; Derivatives thereof, e.g. atropine, cocaine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/10—Laxatives
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
- C07D451/02—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
- C07D451/04—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof with hetero atoms directly attached in position 3 of the 8-azabicyclo [3.2.1] octane or in position 7 of the 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring system
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Emergency Medicine (AREA)
- Epidemiology (AREA)
- Diabetes (AREA)
- Endocrinology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Nutrition Science (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US66878005P | 2005-04-06 | 2005-04-06 | |
| PCT/US2006/012978 WO2006108127A2 (en) | 2005-04-06 | 2006-04-05 | Crystalline form of a quinolinone-carboxamide compound |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EA200702161A1 EA200702161A1 (ru) | 2008-04-28 |
| EA012115B1 true EA012115B1 (ru) | 2009-08-28 |
Family
ID=37074104
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EA200702161A EA012115B1 (ru) | 2005-04-06 | 2006-04-05 | Кристаллическая форма хинолинон-карбоксамидного соединения |
Country Status (29)
| Country | Link |
|---|---|
| US (4) | US7728004B2 (enExample) |
| EP (1) | EP1874766B1 (enExample) |
| JP (2) | JP5230407B2 (enExample) |
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Families Citing this family (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7063671B2 (en) * | 2002-06-21 | 2006-06-20 | Boston Scientific Scimed, Inc. | Electronically activated capture device |
| TWI351282B (en) * | 2004-04-07 | 2011-11-01 | Theravance Inc | Quinolinone-carboxamide compounds as 5-ht4 recepto |
| US7728006B2 (en) * | 2004-04-07 | 2010-06-01 | Theravance, Inc. | Quinolinone-carboxamide compounds as 5-HT4 receptor agonists |
| ES2332808T3 (es) * | 2004-11-05 | 2010-02-12 | Theravance, Inc. | Compuestos agonistas del receptor 5-ht4. |
| US7396933B2 (en) | 2004-11-05 | 2008-07-08 | Theravance, Inc. | Quinolinone-carboxamide compounds |
| TWI377206B (en) * | 2005-04-06 | 2012-11-21 | Theravance Inc | Crystalline form of a quinolinone-carboxamide compound |
| SI1945632T1 (sl) | 2005-11-08 | 2014-03-31 | Vertex Pharmaceuticals Incorporated | Heterocikliäśni modulatorji za prenaĺ alce z atp-vezavno kaseto |
| JP2010527357A (ja) * | 2007-05-17 | 2010-08-12 | セラヴァンス, インコーポレーテッド | 腸の前処置のための運動促進剤 |
| CH698729B1 (de) * | 2007-05-30 | 2009-10-15 | Cerbios Pharma Sa | Stabile, kristalline (6S)-N(5)-Methyl-5, 6,7,8-tetrahydrofolsäure. |
| PT2225230T (pt) * | 2007-12-07 | 2016-12-07 | Vertex Pharma | Formas sólidas de ácido 3-(6(1-(2,2-difluorobenzo[d][1,3] dioxol-5-il) ciclopropanocarboxamido)-3-metilpiridin-2-il) benzoico |
| US8349852B2 (en) | 2009-01-13 | 2013-01-08 | Novartis Ag | Quinazolinone derivatives useful as vanilloid antagonists |
| LT2419104T (lt) | 2009-04-13 | 2018-02-12 | Theravance Biopharma R&D Ip, Llc | 5-ht4 receptoriaus agonistų ir acetilcholinesterazės inhibitorių deriniai, skirti pažinimo sutrikimų gydymui |
| AR080056A1 (es) | 2010-02-01 | 2012-03-07 | Novartis Ag | Derivados de ciclohexil-amida como antagonistas de los receptores de crf |
| JP2013518085A (ja) | 2010-02-01 | 2013-05-20 | ノバルティス アーゲー | CRF−1受容体アンタゴニストとしてのピラゾロ[5,1b]オキサゾール誘導体 |
| US8835444B2 (en) | 2010-02-02 | 2014-09-16 | Novartis Ag | Cyclohexyl amide derivatives as CRF receptor antagonists |
| HRP20211752T1 (hr) | 2010-04-07 | 2022-02-18 | Vertex Pharmaceuticals Incorporated | Farmaceutski pripravci 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioksol-5-il)ciklopropankarboksamido)-3-metilpiridin-2-il)benzojeve kiseline i njihova primjena |
| KR102280372B1 (ko) | 2013-11-12 | 2021-07-22 | 버텍스 파마슈티칼스 인코포레이티드 | Cftr 매개된 질환 치료용 약제학적 조성물의 제조 방법 |
| SG11201912266QA (en) * | 2017-07-31 | 2020-01-30 | Theravance Biopharma R&D Ip Llc | Methods of treating symptoms of gastroparesis using velusetrag |
| US10570127B1 (en) | 2018-11-05 | 2020-02-25 | Renexxion, Llc | Material and methods for the treatment of gastro-intestinal disorders |
| WO2024061960A1 (en) | 2022-09-20 | 2024-03-28 | Alfasigma S.P.A. | Velusetrag for use in the treatment of chronic intestinal pseudo-obstruction (cipo) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0564650A1 (en) * | 1990-12-28 | 1993-10-13 | Kyowa Hakko Kogyo Co., Ltd. | Quinoline derivative |
| WO2005100350A1 (en) * | 2004-04-07 | 2005-10-27 | Theravance, Inc. | Quinolinone-carboxamide compounds as 5-ht4 receptor agonists |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP3122671B2 (ja) * | 1990-05-23 | 2001-01-09 | 協和醗酵工業株式会社 | 複素環式化合物 |
| US5571820A (en) * | 1992-11-20 | 1996-11-05 | Taisho Pharmaceutical Co., Ltd. | Heterocyclic compound |
| JP3829879B2 (ja) * | 1994-05-18 | 2006-10-04 | 大正製薬株式会社 | キノリンカルボン酸誘導体 |
| TW402591B (en) * | 1997-07-11 | 2000-08-21 | Janssen Pharmaceutica Nv | Monocyclic benzamides of 3- or 4-substituted 4-(aminomethyl)-piperidine derivatives |
| US7105195B2 (en) * | 2003-07-25 | 2006-09-12 | General Mills, Inc. | Reduced trans fat product |
| ES2338882T3 (es) | 2003-11-24 | 2010-05-13 | Pfizer, Inc. | Compuestos de acido quinolona-carboxilico que tienen actividad agonista del receptor 5-ht4. |
| US7728006B2 (en) * | 2004-04-07 | 2010-06-01 | Theravance, Inc. | Quinolinone-carboxamide compounds as 5-HT4 receptor agonists |
| US7396933B2 (en) * | 2004-11-05 | 2008-07-08 | Theravance, Inc. | Quinolinone-carboxamide compounds |
| ES2332808T3 (es) * | 2004-11-05 | 2010-02-12 | Theravance, Inc. | Compuestos agonistas del receptor 5-ht4. |
| WO2006088988A1 (en) | 2005-02-17 | 2006-08-24 | Theravance, Inc. | Crystalline form of an indazole-carboxamide compound |
| BRPI0608392A2 (pt) * | 2005-03-02 | 2009-12-29 | Theravance Inc | compostos de quinolinona como agonistas do receptor 5-ht4 |
| TWI377206B (en) * | 2005-04-06 | 2012-11-21 | Theravance Inc | Crystalline form of a quinolinone-carboxamide compound |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0564650A1 (en) * | 1990-12-28 | 1993-10-13 | Kyowa Hakko Kogyo Co., Ltd. | Quinoline derivative |
| WO2005100350A1 (en) * | 2004-04-07 | 2005-10-27 | Theravance, Inc. | Quinolinone-carboxamide compounds as 5-ht4 receptor agonists |
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