JP2017527604A - ｓＧＣ刺激剤 - Google Patents
ｓＧＣ刺激剤 Download PDFInfo
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- JP2017527604A JP2017527604A JP2017515197A JP2017515197A JP2017527604A JP 2017527604 A JP2017527604 A JP 2017527604A JP 2017515197 A JP2017515197 A JP 2017515197A JP 2017515197 A JP2017515197 A JP 2017515197A JP 2017527604 A JP2017527604 A JP 2017527604A
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
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- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
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- Vascular Medicine (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (5)
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| US201562204698P | 2015-08-13 | 2015-08-13 | |
| US62/204,698 | 2015-08-13 | ||
| PCT/US2015/050467 WO2016044446A2 (en) | 2014-09-17 | 2015-09-16 | Sgc stimulators |
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| EP (1) | EP3194386A2 (enExample) |
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| IL (1) | IL251113A0 (enExample) |
| MX (1) | MX2017003518A (enExample) |
| WO (1) | WO2016044446A2 (enExample) |
Cited By (1)
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| KR20200128707A (ko) * | 2018-03-07 | 2020-11-16 | 사이클리온 테라퓨틱스, 인크. | 가용성 구아닐레이트 시클라제 자극제의 제조 방법 |
Families Citing this family (34)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BR112018000254A2 (pt) | 2015-07-07 | 2018-09-04 | H Lundbeck As | inibidores de pde9 com cadeia principal de imidazotriazinona e cadeia principal de imidazopirazinona para o tratamento de doenças periféricas |
| JP2019502686A (ja) | 2015-12-14 | 2019-01-31 | アイアンウッド ファーマシューティカルズ インコーポレイテッド | 消化管括約筋機能障害の治療へのｓＧＣ刺激薬の使用 |
| WO2017107052A1 (en) | 2015-12-22 | 2017-06-29 | Merck Sharp & Dohme Corp. | Soluble guanylate cyclase stimulators |
| CN105859726B (zh) * | 2016-05-18 | 2018-07-13 | 南京富润凯德生物医药有限公司 | 一种嘧啶并环中选择性脱卤素的方法 |
| ES2963563T3 (es) | 2016-07-07 | 2024-03-27 | Cyclerion Therapeutics Inc | Procesos novedosos para preparar estimuladores de guanilato ciclasa soluble |
| EP3872080B1 (en) * | 2016-09-02 | 2023-08-16 | Cyclerion Therapeutics, Inc. | Fused bicyclic sgc stimulators |
| JP7101688B2 (ja) | 2016-10-11 | 2022-07-15 | バイエル・ファルマ・アクティエンゲゼルシャフト | ｓＧＣ刺激薬とミネラルコルチコイド受容体拮抗薬とを含む組み合わせ |
| WO2018069148A1 (de) | 2016-10-11 | 2018-04-19 | Bayer Pharma Aktiengesellschaft | Kombination enthaltend sgc aktivatoren und mineralocorticoid-rezeptor-antagonisten |
| US20190381039A1 (en) | 2016-12-13 | 2019-12-19 | Cyclerion Therapeutics, Inc. | USE OF sGC STIMULATORS FOR THE TREATMENT OF ESOPHAGEAL MOTILITY DISORDERS |
| AR112673A1 (es) | 2017-08-11 | 2019-11-27 | Syngenta Participations Ag | Derivados de pirazol activos como plaguicidas |
| US11252963B2 (en) | 2017-08-11 | 2022-02-22 | Syngenta Participations Ag | Pesticidally active pyrazole derivatives |
| WO2019030355A1 (en) | 2017-08-11 | 2019-02-14 | Syngenta Participations Ag | ACTIVE PYRAZOLE DERIVATIVES ON THE PESTICIDE PLAN |
| WO2019081456A1 (en) | 2017-10-24 | 2019-05-02 | Bayer Aktiengesellschaft | USE OF SGC ACTIVATORS AND STIMULATORS COMPRISING A BETA2 SUBUNIT |
| EP3498298A1 (en) | 2017-12-15 | 2019-06-19 | Bayer AG | The use of sgc stimulators and sgc activators alone or in combination with pde5 inhibitors for the treatment of bone disorders including osteogenesis imperfecta (oi) |
| CA3092683A1 (en) | 2018-03-07 | 2019-09-12 | Cyclerion Therapeutics, Inc. | Crystalline forms of an sgc stimulator |
| CN112055584A (zh) | 2018-04-30 | 2020-12-08 | 拜耳公司 | sGC活化剂和sGC刺激剂用于治疗认知障碍的用途 |
| JP2021523201A (ja) | 2018-05-15 | 2021-09-02 | バイエル アクチェンゲゼルシャフトＢａｙｅｒ Ａｋｔｉｅｎｇｅｓｅｌｌｓｃｈａｆｔ | 神経線維感作に関連する疾患を治療するための１，３−チアゾール−２−イル置換ベンズアミド |
| US11508483B2 (en) | 2018-05-30 | 2022-11-22 | Adverio Pharma Gmbh | Method of identifying a subgroup of patients suffering from dcSSc which benefits from a treatment with sGC stimulators and sGC activators in a higher degree than a control group |
| JP7542518B2 (ja) | 2018-07-11 | 2024-08-30 | ティセント セラピューティクス インコーポレーテッド | ミトコンドリア（ｍｉｔｏｃｈｏｎｒｉａｌ）障害の処置のためのｓＧＣ刺激剤の使用 |
| US11066404B2 (en) | 2018-10-11 | 2021-07-20 | Incyte Corporation | Dihydropyrido[2,3-d]pyrimidinone compounds as CDK2 inhibitors |
| US20220128561A1 (en) | 2019-01-17 | 2022-04-28 | Bayer Aktiengesellschaft | Methods to determine whether a subject is suitable of being treated with an agonist of soluble gyanylyl cyclase (sgc) |
| WO2020164994A1 (en) | 2019-02-13 | 2020-08-20 | Syngenta Crop Protection Ag | Pesticidally active pyrazole derivatives |
| US11384083B2 (en) | 2019-02-15 | 2022-07-12 | Incyte Corporation | Substituted spiro[cyclopropane-1,5′-pyrrolo[2,3-d]pyrimidin]-6′(7′h)-ones as CDK2 inhibitors |
| TW202100520A (zh) | 2019-03-05 | 2021-01-01 | 美商英塞特公司 | 作為cdk2 抑制劑之吡唑基嘧啶基胺化合物 |
| WO2020205560A1 (en) | 2019-03-29 | 2020-10-08 | Incyte Corporation | Sulfonylamide compounds as cdk2 inhibitors |
| US11447494B2 (en) | 2019-05-01 | 2022-09-20 | Incyte Corporation | Tricyclic amine compounds as CDK2 inhibitors |
| US11440914B2 (en) | 2019-05-01 | 2022-09-13 | Incyte Corporation | Tricyclic amine compounds as CDK2 inhibitors |
| CN116348458A (zh) | 2019-08-14 | 2023-06-27 | 因赛特公司 | 作为cdk2抑制剂的咪唑基嘧啶基胺化合物 |
| CN119930611A (zh) | 2019-10-11 | 2025-05-06 | 因赛特公司 | 作为cdk2抑制剂的双环胺 |
| CN111423377B (zh) * | 2020-05-12 | 2021-06-01 | 中国药科大学 | 5-氨基-1h-吡唑衍生物、制备方法及医药用途 |
| US20240025904A1 (en) * | 2020-10-27 | 2024-01-25 | Cardurion Pharmaceuticals, Inc. | Pde9 inhibitors for treating cardiac failure |
| US11981671B2 (en) | 2021-06-21 | 2024-05-14 | Incyte Corporation | Bicyclic pyrazolyl amines as CDK2 inhibitors |
| US11976073B2 (en) | 2021-12-10 | 2024-05-07 | Incyte Corporation | Bicyclic amines as CDK2 inhibitors |
| WO2025102245A1 (zh) * | 2023-11-14 | 2025-05-22 | 浙江天宇药业股份有限公司 | 一种双重内皮素受体拮抗剂阿普昔腾坦的合成方法 |
Family Cites Families (98)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3773919A (en) | 1969-10-23 | 1973-11-20 | Du Pont | Polylactide-drug mixtures |
| US3995631A (en) | 1971-01-13 | 1976-12-07 | Alza Corporation | Osmotic dispenser with means for dispensing active agent responsive to osmotic gradient |
| US4203440A (en) | 1978-10-23 | 1980-05-20 | Alza Corporation | Device having variable volume chamber for dispensing useful agent |
| US4627850A (en) | 1983-11-02 | 1986-12-09 | Alza Corporation | Osmotic capsule |
| DE3660408D1 (en) | 1985-02-27 | 1988-08-25 | Oerlikon Buehrle Ag | Apparatus for measuring the vibrations of a spiral bevel gear transmission in a gear-testing machine |
| IL92966A (en) | 1989-01-12 | 1995-07-31 | Pfizer | Dispensing devices powered by hydrogel |
| US5721365A (en) | 1989-09-15 | 1998-02-24 | Us Health | N-substituted piperazine NONOates |
| US5304121A (en) | 1990-12-28 | 1994-04-19 | Boston Scientific Corporation | Drug delivery system making use of a hydrogel polymer coating |
| US5324280A (en) | 1990-04-02 | 1994-06-28 | Alza Corporation | Osmotic dosage system for delivering a formulation comprising liquid carrier and drug |
| US5155137A (en) | 1990-09-20 | 1992-10-13 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Complexes of nitric oxide with polyamines |
| AU668107B2 (en) | 1991-09-24 | 1996-04-26 | United States Of America, Represented By The Secretary, Department Of Health And Human Services, The | Oxygen substituted derivatives of nucleophile-nitric oxide adducts as nitric oxide donor prodrugs |
| GB9127531D0 (en) | 1991-12-31 | 1992-02-19 | Fujisawa Pharmaceutical Co | Heterocyclic compound |
| US5814666A (en) | 1992-04-13 | 1998-09-29 | The United States As Represented By The Department Of Health And Human Services | Encapsulated and non-encapsulated nitric oxide generators used as antimicrobial agents |
| US5691423A (en) | 1992-08-24 | 1997-11-25 | The United States Of America As Represented By The Department Of Health And Human Services | Polysaccharide-bound nitric oxide-nucleophile adducts |
| US5910316A (en) | 1992-08-24 | 1999-06-08 | The United States Of America, As Represented By The Department Of Health And Human Services | Use of nitric oxide-releasing agents to treat impotency |
| US5632981A (en) | 1992-08-24 | 1997-05-27 | The United States Of America As Represented By The Department Of Health And Human Services | Biopolymer-bound nitric oxide-releasing compositions, pharmaceutical compositions incorporating same and methods of treating biological disorders using same |
| US5405919A (en) | 1992-08-24 | 1995-04-11 | The United States Of America As Represented By The Secretary Of Health And Human Services | Polymer-bound nitric oxide/nucleophile adduct compositions, pharmaceutical compositions and methods of treating biological disorders |
| US5716981A (en) | 1993-07-19 | 1998-02-10 | Angiogenesis Technologies, Inc. | Anti-angiogenic compositions and methods of use |
| EP0722320B1 (en) | 1993-10-08 | 2000-07-19 | THE UNITED STATES OF AMERICA, as represented by the Secretary of the Department of Health and Human Services | Use of nitric oxide-releasing compounds as medicaments for hypoxic cell radiation sensitization |
| JP2928079B2 (ja) | 1994-02-14 | 1999-07-28 | 永信薬品工業股▲ふん▼有限公司 | １−（置換ベンジル）−３−（置換アリール）縮合ピラゾール類、その製造法及びその用途 |
| US5700830A (en) | 1994-11-22 | 1997-12-23 | The United States Of America As Represented By The Department Of Health And Human Services | Use of nitric oxide-releasing agents for reducing metastasis risk |
| US6099562A (en) | 1996-06-13 | 2000-08-08 | Schneider (Usa) Inc. | Drug coating with topcoat |
| ATE337294T1 (de) | 1995-06-21 | 2006-09-15 | Shionogi & Co | Bizyklische aminoderivate und enthaltende pgd2- antagonisten |
| US5714511A (en) | 1995-07-31 | 1998-02-03 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Selective prevention of organ injury in sepsis and shock using selection release of nitric oxide in vulnerable organs |
| JP4120993B2 (ja) | 1996-12-12 | 2008-07-16 | 塩野義製薬株式会社 | ヘテロ環縮合ベンゼンカルボン酸アミド誘導体およびそれを含有するｐｇｄ２拮抗剤 |
| CA2274591C (en) | 1996-12-13 | 2005-06-14 | Shionogi & Co., Ltd. | Benzothiophenecarboxamide derivatives and pgd2 antagonists comprising them |
| DE19744026A1 (de) | 1997-10-06 | 1999-04-08 | Hoechst Marion Roussel De Gmbh | Pyrazol-Derivate, ihre Herstellung und ihre Verwendung in Arzneimitteln |
| DE19830430A1 (de) | 1998-07-08 | 2000-01-13 | Hoechst Marion Roussel De Gmbh | Schwefelsubstituierte Sulfonylamino-carbonsäure-N-arylamide, ihre Herstellung, ihre Verwendung und sie enthaltende pharmazeutische Präparate |
| KR100720844B1 (ko) | 1998-07-08 | 2007-05-25 | 사노피-아벤티스 도이칠란트 게엠베하 | 황 치환된 설포닐아미노카복실산 ｎ-아릴아미드, 이의 제조방법, 및 이를 함유하는 약제학적 제제 |
| DE19834047A1 (de) | 1998-07-29 | 2000-02-03 | Bayer Ag | Substituierte Pyrazolderivate |
| DE19834044A1 (de) | 1998-07-29 | 2000-02-03 | Bayer Ag | Neue substituierte Pyrazolderivate |
| GB9824310D0 (en) | 1998-11-05 | 1998-12-30 | Univ London | Activators of soluble guanylate cyclase |
| AU765909C (en) | 1998-12-17 | 2004-09-23 | Alza Corporation | Conversion of liquid filled gelatin capsules into controlled release systems by multiple coatings |
| US6342249B1 (en) | 1998-12-23 | 2002-01-29 | Alza Corporation | Controlled release liquid active agent formulation dosage forms |
| DE19942809A1 (de) | 1999-09-08 | 2001-03-15 | Bayer Ag | Verfahren zur Herstellung substituierter Pyrimidinderivate |
| DE19943635A1 (de) | 1999-09-13 | 2001-03-15 | Bayer Ag | Neuartige Aminodicarbonsäurederivate mit pharmazeutischen Eigenschaften |
| ATE311200T1 (de) | 2000-04-12 | 2005-12-15 | Merck Frosst Canada Inc | Verfahren und zusammensetzungen zur behandlung von allergischen zuständen mit pgd2 rezeptor antagonisten |
| US20010051624A1 (en) | 2000-04-12 | 2001-12-13 | Jones Thomas R. | Method and compositions for the treatment of allergic conditions using PGD2 receptor antagonists |
| US6878522B2 (en) | 2000-07-07 | 2005-04-12 | Baiyong Li | Methods for the identification of compounds useful for the treatment of disease states mediated by prostaglandin D2 |
| PE20020870A1 (es) | 2001-02-13 | 2002-11-18 | Aventis Pharma Gmbh | 6,7,8,9-tetrahidro-5h-benzocicloheptenil aminas aciladas |
| TWI241190B (en) | 2001-02-13 | 2005-10-11 | Aventis Pharma Gmbh | 4-Fluoro-N-indan-2-yl benzamide and its use as pharmaceutical |
| TWI243164B (en) | 2001-02-13 | 2005-11-11 | Aventis Pharma Gmbh | Acylated indanyl amines and their use as pharmaceuticals |
| PE20020856A1 (es) | 2001-02-13 | 2002-11-11 | Aventis Pharma Gmbh | 1,2,3,4-tetrahidronaftil aminas aciladas |
| US6511911B1 (en) | 2001-04-03 | 2003-01-28 | Advanced Micro Devices, Inc. | Metal gate stack with etch stop layer |
| KR20040044856A (ko) | 2001-09-07 | 2004-05-31 | 오노 야꾸힝 고교 가부시키가이샤 | 인돌 유도체 화합물 |
| JP4292402B2 (ja) | 2001-09-07 | 2009-07-08 | 小野薬品工業株式会社 | インドール誘導体化合物、それらの製造方法およびそれらを有効成分として含有する薬剤 |
| US6806380B2 (en) | 2001-10-02 | 2004-10-19 | Lexicon Pharmaceuticals, Inc. | Modified safe and efficient process for the environmentally friendly synthesis of imidoesters |
| SE0200356D0 (sv) | 2002-02-05 | 2002-02-05 | Astrazeneca Ab | Novel use |
| SE0200411D0 (sv) | 2002-02-05 | 2002-02-05 | Astrazeneca Ab | Novel use |
| DE10216145A1 (de) | 2002-04-12 | 2003-10-23 | Bayer Ag | Verwendung von Stimulatoren der löslichen Guanylatcyclase zur Behandlung von Glaukom |
| DE10220570A1 (de) | 2002-05-08 | 2003-11-20 | Bayer Ag | Carbamat-substituierte Pyrazolopyridine |
| WO2003097042A1 (en) | 2002-05-16 | 2003-11-27 | Shionogi & Co., Ltd. | Pgd2 receptor antagonist |
| WO2003097598A1 (en) | 2002-05-16 | 2003-11-27 | Shionogi & Co., Ltd. | Compound exhibiting pgd 2 receptor antagonism |
| SE0201635D0 (sv) | 2002-05-30 | 2002-05-30 | Astrazeneca Ab | Novel compounds |
| TW200307542A (en) | 2002-05-30 | 2003-12-16 | Astrazeneca Ab | Novel compounds |
| SE0202241D0 (sv) | 2002-07-17 | 2002-07-17 | Astrazeneca Ab | Novel Compounds |
| PL376156A1 (en) | 2002-10-04 | 2005-12-27 | Millennium Pharmaceuticals, Inc. | Pgd2 receptor antagonists for the treatment of inflammatory diseases |
| NZ541234A (en) | 2002-12-20 | 2008-06-30 | Amgen Inc | Asthma and allergic inflammation modulators |
| AU2004212490B2 (en) | 2003-02-10 | 2008-05-15 | Amgen Inc. | Vanilloid receptor ligands and their use in treatments |
| TW200423930A (en) | 2003-02-18 | 2004-11-16 | Hoffmann La Roche | Non-nucleoside reverse transcriptase inhibitors |
| KR20060033033A (ko) | 2003-08-04 | 2006-04-18 | 화이자 프로덕츠 인크. | 콜레스테릴 에스테르 전달 단백질 억제제의 제어 방출 및ｈｍｇ-ｃｏａ 리덕타제 억제제의 순간 방출을 제공하는제형 |
| UY28526A1 (es) | 2003-09-24 | 2005-04-29 | Boehringer Ingelheim Pharma | Miméticos de glucocorticoides, métodos de preparación composiciones farmacéuticas y usos de los mismos |
| US8309608B2 (en) | 2003-11-06 | 2012-11-13 | Sanofi-Aventis Deutschland Gmbh | Use of eNOS transcription enhancers in the cell therapy of ischemic heart diseases |
| CA2698332C (en) | 2007-09-06 | 2012-08-21 | Merck Sharp & Dohme Corp. | Pyrazole derivatives as soluble guanylate cyclase activators |
| US7947664B2 (en) | 2008-01-24 | 2011-05-24 | Merck Sharp & Dohme Corp. | Angiotensin II receptor antagonists |
| CN102164604A (zh) | 2008-07-24 | 2011-08-24 | 百时美施贵宝公司 | 用作激酶调节剂的稠合杂环化合物 |
| WO2010037225A1 (en) * | 2008-10-02 | 2010-04-08 | Merck Frosst Canada Ltd. | Heteroaromatic compounds as inhibitors of stearoyl-coenzyme a delta-9 desaturase |
| US8741910B2 (en) | 2008-11-25 | 2014-06-03 | Merck Sharp & Dohme Corp. | Soluble guanylate cyclase activators |
| CN102414194A (zh) | 2009-02-26 | 2012-04-11 | 默沙东公司 | 可溶性鸟苷酸环化酶激活剂 |
| KR101793304B1 (ko) | 2010-02-05 | 2017-11-02 | 아드베리오 파마 게엠베하 | 낭성 섬유증의 치료를 위한, 단독으로의 및 ＰＤＥ5 억제제와 조합된 ｓＧＣ 자극제 또는 ｓＧＣ 활성화제 |
| US20130178475A1 (en) * | 2010-03-17 | 2013-07-11 | Ironwood Pharmaceuticals, Inc. | sGC STIMULATORS |
| WO2011119518A1 (en) | 2010-03-25 | 2011-09-29 | Merck Sharp & Dohme Corp. | Soluble guanylate cyclase activators |
| MA34330B1 (fr) | 2010-05-27 | 2013-06-01 | Merck Sharp & Dohme | Activateurs de guanylate cyclase soluble |
| EP2579717A4 (en) * | 2010-06-09 | 2013-12-11 | Merck Sharp & Dohme | POSITIVE ALLOSTERIC MODULATORS OF MGLUR2 |
| WO2012003405A1 (en) * | 2010-06-30 | 2012-01-05 | Ironwood Pharmaceuticals, Inc. | Sgc stimulators |
| DE102010040233A1 (de) | 2010-09-03 | 2012-03-08 | Bayer Schering Pharma Aktiengesellschaft | Bicyclische Aza-Heterocyclen und ihre Verwendung |
| EP2632551B1 (en) | 2010-10-28 | 2016-07-06 | Merck Sharp & Dohme Corp. | Soluble guanylate cyclase activators |
| NZ609955A (en) * | 2010-11-09 | 2015-05-29 | Ironwood Pharmaceuticals Inc | Sgc stimulators |
| KR101719556B1 (ko) | 2011-03-30 | 2017-03-24 | 주식회사 레고켐 바이오사이언스 | 신규한 세파로스포린 유도체 및 이를 함유하는 의약 조성물 |
| PH12014500460A1 (en) | 2011-09-02 | 2014-04-14 | Bayer Ip Gmbh | Substituted annellated pyrimidine and the use thereof |
| CN104066731B (zh) * | 2011-12-27 | 2016-06-15 | 铁木医药有限公司 | 可用作sgc刺激剂的2-苄基、3-(嘧啶-2-基)取代的吡唑类 |
| DE102012200352A1 (de) | 2012-01-11 | 2013-07-11 | Bayer Intellectual Property Gmbh | Substituierte, annellierte Imidazole und Pyrazole und ihre Verwendung |
| ES2644781T3 (es) | 2012-03-06 | 2017-11-30 | Bayer Intellectual Property Gmbh | Azabiciclos sustituidos y su uso |
| US9309235B2 (en) * | 2012-09-18 | 2016-04-12 | Ironwood Pharmaceuticals, Inc. | SGC stimulators |
| US9487508B2 (en) * | 2012-09-19 | 2016-11-08 | Ironwood Pharmaceuticals, Inc. | SGC stimulators |
| US9637491B2 (en) * | 2012-10-19 | 2017-05-02 | Origenis Gmbh | Pyrazolo[4,3-D]pyrimidines as kinase inhibitors |
| US9908887B2 (en) | 2012-12-21 | 2018-03-06 | Epizyme, Inc. | PRMT5 inhibitors and uses thereof |
| SI2970243T1 (sl) | 2013-03-15 | 2020-04-30 | Cyclerion Therapeutics, Inc. | SGC stimulatorji |
| KR20160042039A (ko) * | 2013-08-09 | 2016-04-18 | 알데릭스, 인코포레이티드 | 인산염 수송을 억제하기 위한 화합물 및 방법 |
| EP3092231B1 (en) * | 2013-12-11 | 2018-06-27 | Ironwood Pharmaceuticals, Inc. | Sgc stimulators |
| EP3094327A1 (en) * | 2014-01-13 | 2016-11-23 | Ironwood Pharmaceuticals, Inc. | USE OF sGC STIMULATORS FOR THE TREATMENT OF NEUROMUSCULAR DISORDERS |
| JP2017527605A (ja) * | 2014-09-17 | 2017-09-21 | アイアンウッド ファーマシューティカルズ インコーポレイテッド | ｓＧＣ刺激剤 |
| US20170298055A1 (en) * | 2014-09-17 | 2017-10-19 | Ironwood Pharmaceuticals, Inc. | sGC STIMULATORS |
| CA2959757A1 (en) * | 2014-09-17 | 2016-03-24 | Ironwood Pharmaceuticals, Inc. | Pyrazole derivatives as sgc stimulators |
| JP2019502686A (ja) * | 2015-12-14 | 2019-01-31 | アイアンウッド ファーマシューティカルズ インコーポレイテッド | 消化管括約筋機能障害の治療へのｓＧＣ刺激薬の使用 |
| CA3012001A1 (en) * | 2016-02-01 | 2017-08-10 | Ironwood Pharmaceuticals, Inc. | Use of sgc stimulators for the treatment of nonalcoholic steatohepatitis (nash) |
| EP3872080B1 (en) * | 2016-09-02 | 2023-08-16 | Cyclerion Therapeutics, Inc. | Fused bicyclic sgc stimulators |
| US20190381039A1 (en) * | 2016-12-13 | 2019-12-19 | Cyclerion Therapeutics, Inc. | USE OF sGC STIMULATORS FOR THE TREATMENT OF ESOPHAGEAL MOTILITY DISORDERS |
-
2015
- 2015-09-16 CA CA2961489A patent/CA2961489A1/en not_active Abandoned
- 2015-09-16 CN CN201580062197.4A patent/CN107406421A/zh active Pending
- 2015-09-16 JP JP2017515197A patent/JP2017527604A/ja not_active Withdrawn
- 2015-09-16 US US15/511,888 patent/US10844064B2/en not_active Expired - Fee Related
- 2015-09-16 EP EP15778428.1A patent/EP3194386A2/en not_active Withdrawn
- 2015-09-16 MX MX2017003518A patent/MX2017003518A/es unknown
- 2015-09-16 AU AU2015317823A patent/AU2015317823A1/en not_active Abandoned
- 2015-09-16 WO PCT/US2015/050467 patent/WO2016044446A2/en not_active Ceased
-
2017
- 2017-03-13 IL IL251113A patent/IL251113A0/en unknown
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20200128707A (ko) * | 2018-03-07 | 2020-11-16 | 사이클리온 테라퓨틱스, 인크. | 가용성 구아닐레이트 시클라제 자극제의 제조 방법 |
| JP2021515018A (ja) * | 2018-03-07 | 2021-06-17 | サイクレリオン・セラピューティクス，インコーポレーテッド | 可溶性グアニル酸シクラーゼ刺激薬を調製するための方法 |
| JP7406692B2 (ja) | 2018-03-07 | 2023-12-28 | ティセント セラピューティクス インコーポレーテッド | 可溶性グアニル酸シクラーゼ刺激薬を調製するための方法 |
| KR102926111B1 (ko) | 2018-03-07 | 2026-02-11 | 티센토 쎄라퓨틱스 인크. | 가용성 구아닐레이트 시클라제 자극제의 제조 방법 |
Also Published As
| Publication number | Publication date |
|---|---|
| AU2015317823A1 (en) | 2017-03-23 |
| US20180155345A1 (en) | 2018-06-07 |
| WO2016044446A3 (en) | 2016-06-16 |
| IL251113A0 (en) | 2017-04-30 |
| MX2017003518A (es) | 2017-07-28 |
| CN107406421A (zh) | 2017-11-28 |
| US10844064B2 (en) | 2020-11-24 |
| EP3194386A2 (en) | 2017-07-26 |
| WO2016044446A2 (en) | 2016-03-24 |
| CA2961489A1 (en) | 2016-03-24 |
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