CN107406421A - sGC刺激物 - Google Patents
sGC刺激物 Download PDFInfo
- Publication number
- CN107406421A CN107406421A CN201580062197.4A CN201580062197A CN107406421A CN 107406421 A CN107406421 A CN 107406421A CN 201580062197 A CN201580062197 A CN 201580062197A CN 107406421 A CN107406421 A CN 107406421A
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- Prior art keywords
- alkyl
- yuan
- ring
- hetero
- circle heterocycles
- Prior art date
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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
-
- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
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Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
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| US201462051576P | 2014-09-17 | 2014-09-17 | |
| US62/051,576 | 2014-09-17 | ||
| 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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| CN107406421A true CN107406421A (zh) | 2017-11-28 |
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| CN201580062197.4A Pending CN107406421A (zh) | 2014-09-17 | 2015-09-16 | sGC刺激物 |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US10844064B2 (2) |
| EP (1) | EP3194386A2 (2) |
| JP (1) | JP2017527604A (2) |
| CN (1) | CN107406421A (2) |
| AU (1) | AU2015317823A1 (2) |
| CA (1) | CA2961489A1 (2) |
| IL (1) | IL251113A0 (2) |
| MX (1) | MX2017003518A (2) |
| WO (1) | WO2016044446A2 (2) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111423377A (zh) * | 2020-05-12 | 2020-07-17 | 中国药科大学 | 5-氨基-1h-吡唑衍生物、制备方法及医药用途 |
| CN111836811A (zh) * | 2018-03-07 | 2020-10-27 | 塞科里昂医疗股份有限公司 | 制备可溶性鸟苷酸环化酶刺激剂的方法 |
| 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 |
Families Citing this family (32)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PT3865484T (pt) | 2015-07-07 | 2024-01-30 | H Lundbeck As | Inibidor da pde9 com esqueleto de imidazo pirazinona para tratamento de doenças periféricas |
| US20180344735A1 (en) | 2015-12-14 | 2018-12-06 | Ironwood Pharmaceuticals, Inc. | USE OF sGC STIMULATORS FOR THE TREATMENT OF GASTROINTESTINAL SPHINCTER DYSFUNCTION |
| 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 |
| CN109563077B (zh) | 2016-07-07 | 2026-03-10 | 赛克里翁治疗有限公司 | 用于制备可溶性鸟苷酸环化酶刺激剂的新方法 |
| SI3507291T1 (sl) * | 2016-09-02 | 2021-11-30 | Cyclerion Therapeutics, Inc. | Kondenzirani biciklični SGS stimulatorji |
| EP3525779B1 (de) | 2016-10-11 | 2024-06-05 | Bayer Pharma Aktiengesellschaft | Kombination enthaltend den sgc stimulator vericuguat und den mineralcorticoid-rezeptor-antagonist finerenone |
| CN109890379A (zh) | 2016-10-11 | 2019-06-14 | 拜耳制药股份公司 | 包含sGC活化剂和盐皮质激素受体拮抗剂的组合产品 |
| EP3554488A2 (en) | 2016-12-13 | 2019-10-23 | 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 |
| EP3665167B1 (en) | 2017-08-11 | 2022-11-30 | Syngenta Participations AG | Pesticidally active pyrazole derivatives |
| US11252963B2 (en) | 2017-08-11 | 2022-02-22 | Syngenta Participations Ag | Pesticidally active pyrazole derivatives |
| 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) |
| AU2019231724B2 (en) | 2018-03-07 | 2024-06-27 | Tisento Therapeutics Inc. | Crystalline forms of an sGC stimulator |
| EP3787610A1 (en) | 2018-04-30 | 2021-03-10 | Bayer Aktiengesellschaft | The use of sgc activators and sgc stimulators for the treatment of cognitive impairment |
| EP3793553A1 (en) | 2018-05-15 | 2021-03-24 | Bayer Aktiengesellschaft | 1,3-thiazol-2-yl substituted benzamides for the treatment of diseases associated with nerve fiber sensitization |
| EP3574905A1 (en) | 2018-05-30 | 2019-12-04 | 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 |
| KR20250141845A (ko) | 2018-07-11 | 2025-09-29 | 티센토 쎄라퓨틱스 인크. | 미토콘드리아 장애의 치료를 위한 sGC 자극제의 용도 |
| 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 |
| WO2020223469A1 (en) | 2019-05-01 | 2020-11-05 | Incyte Corporation | N-(1-(methylsulfonyl)piperidin-4-yl)-4,5-di hydro-1h-imidazo[4,5-h]quinazolin-8-amine derivatives and related compounds as cyclin-dependent kinase 2 (cdk2) inhibitors for treating cancer |
| US11447494B2 (en) | 2019-05-01 | 2022-09-20 | Incyte Corporation | Tricyclic amine compounds as CDK2 inhibitors |
| CA3150681A1 (en) | 2019-08-14 | 2021-02-18 | Incyte Corporation | Imidazolyl pyrimidinylamine compounds as cdk2 inhibitors |
| US11851426B2 (en) | 2019-10-11 | 2023-12-26 | Incyte Corporation | Bicyclic amines as CDK2 inhibitors |
| 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 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2012003405A1 (en) * | 2010-06-30 | 2012-01-05 | Ironwood Pharmaceuticals, Inc. | Sgc stimulators |
| WO2013101830A1 (en) * | 2011-12-27 | 2013-07-04 | Ironwood Pharmaceuticals, Inc. | 2 - benzyl, 3 - (pyrimidin- 2 -yl) substituted pyrazoles useful as sgc stimulators |
Family Cites Families (96)
| 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 |
| EP0192963B1 (de) | 1985-02-27 | 1988-07-20 | Werkzeugmaschinenfabrik Oerlikon-Bührle AG | Schwingungsmesseinrichtung für ein Spiralkegelradgetriebe auf einer Zahnradprüfmaschine |
| 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 |
| WO1993007114A1 (en) | 1991-09-24 | 1993-04-15 | The United States Of America, Represented By The Secretary, Department Of Health And Human Services | 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 |
| 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 |
| 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 |
| US5886026A (en) | 1993-07-19 | 1999-03-23 | Angiotech Pharmaceuticals Inc. | Anti-angiogenic compositions and methods of use |
| CA2173738A1 (en) | 1993-10-08 | 1995-04-20 | James B. Mitchell | Use of nitric oxide-releasing compounds as hypoxic cell radiation sensitizers |
| 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 |
| CN1134411C (zh) | 1995-06-21 | 2004-01-14 | 盐野义制药株式会社 | 双环氨基衍生物及含有此类化合物的前列腺素d2拮抗剂 |
| 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 |
| EP0945450B1 (en) | 1996-12-12 | 2005-05-11 | Shionogi & Co., Ltd. | Fused heterocyclic benzenecarboxylic acid amide derivatives and pgd2 antagonists containing the same |
| PL191760B1 (pl) | 1996-12-13 | 2006-06-30 | Shionogi & Co | Związki, pochodne benzotiofenokarboksyamidu, związki pośrednie, kompozycja farmaceutyczna zawierająca te pochodne oraz lek do leczenia blokady nosa |
| DE19744026A1 (de) | 1997-10-06 | 1999-04-08 | Hoechst Marion Roussel De Gmbh | Pyrazol-Derivate, ihre Herstellung und ihre Verwendung in Arzneimitteln |
| CZ302691B6 (cs) | 1998-07-08 | 2011-09-07 | Sanofi - Aventis Deutschland GmbH | N-Arylamidová sloucenina, zpusob její prípravy, farmaceutický prostredek tuto slouceninu obsahující, tato sloucenina pro použití jako aktivátor a pro použití k terapii nebo profylaxi |
| 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 |
| DE19834044A1 (de) | 1998-07-29 | 2000-02-03 | Bayer Ag | Neue substituierte Pyrazolderivate |
| DE19834047A1 (de) | 1998-07-29 | 2000-02-03 | Bayer Ag | Substituierte Pyrazolderivate |
| GB9824310D0 (en) | 1998-11-05 | 1998-12-30 | Univ London | Activators of soluble guanylate cyclase |
| PT1140012E (pt) | 1998-12-17 | 2004-05-31 | Alza Corp | Conversao de capsulas de gelatina cheias com liquido em sistemas de libertacao controlada por camadas multiplas |
| 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 |
| US20010051624A1 (en) | 2000-04-12 | 2001-12-13 | Jones Thomas R. | Method and compositions for the treatment of allergic conditions using PGD2 receptor antagonists |
| ATE311200T1 (de) | 2000-04-12 | 2005-12-15 | Merck Frosst Canada Inc | Verfahren und zusammensetzungen zur behandlung von allergischen zuständen mit pgd2 rezeptor antagonisten |
| 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 |
| MY136316A (en) | 2001-02-13 | 2008-09-30 | Sanofi Aventis Deutschland | Acylated 6,7,8,9-tetrahydro-5h-benzocycloheptenyl amines and their use as pharmaceutical. |
| PE20020856A1 (es) | 2001-02-13 | 2002-11-11 | Aventis Pharma Gmbh | 1,2,3,4-tetrahidronaftil aminas aciladas |
| TWI243164B (en) | 2001-02-13 | 2005-11-11 | Aventis Pharma Gmbh | Acylated indanyl amines and their use as pharmaceuticals |
| TWI241190B (en) | 2001-02-13 | 2005-10-11 | Aventis Pharma Gmbh | 4-Fluoro-N-indan-2-yl benzamide and its use as pharmaceutical |
| US6511911B1 (en) | 2001-04-03 | 2003-01-28 | Advanced Micro Devices, Inc. | Metal gate stack with etch stop layer |
| CA2459515A1 (en) | 2001-09-07 | 2003-03-20 | Kazuhiko Torisu | Indole derivatives |
| EP1424325A4 (en) | 2001-09-07 | 2005-12-21 | Ono Pharmaceutical Co | INDOLE DERIVATIVES, METHOD FOR THE PRODUCTION THEREOF AND MEDICAMENTS CONTAINING THEM AS AN ACTIVE AGENT |
| US6806380B2 (en) | 2001-10-02 | 2004-10-19 | Lexicon Pharmaceuticals, Inc. | Modified safe and efficient process for the environmentally friendly synthesis of imidoesters |
| SE0200411D0 (sv) | 2002-02-05 | 2002-02-05 | Astrazeneca Ab | Novel use |
| SE0200356D0 (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 |
| AU2003231509A1 (en) | 2002-05-16 | 2003-12-02 | Shionogi And Co., Ltd. | Compound exhibiting pgd 2 receptor antagonism |
| WO2003097042A1 (en) | 2002-05-16 | 2003-11-27 | Shionogi & Co., Ltd. | Pgd2 receptor antagonist |
| TW200307542A (en) | 2002-05-30 | 2003-12-16 | Astrazeneca Ab | Novel compounds |
| SE0201635D0 (sv) | 2002-05-30 | 2002-05-30 | Astrazeneca Ab | Novel compounds |
| SE0202241D0 (sv) | 2002-07-17 | 2002-07-17 | Astrazeneca Ab | Novel Compounds |
| WO2004032848A2 (en) | 2002-10-04 | 2004-04-22 | Millennium Pharmaceuticals, Inc. | Pgd2 receptor antagonists for the treatment of inflammatory diseases |
| PL377314A1 (pl) | 2002-12-20 | 2006-01-23 | Amgen Inc. | Modulatory astmy i zapaleń na tle alergicznym |
| JP2006517234A (ja) | 2003-02-10 | 2006-07-20 | アムジエン・インコーポレーテツド | バニロイド受容体リガンドおよび治療におけるこれらのリガンドの使用 |
| TW200423930A (en) | 2003-02-18 | 2004-11-16 | Hoffmann La Roche | Non-nucleoside reverse transcriptase inhibitors |
| BRPI0413363A (pt) | 2003-08-04 | 2006-10-10 | Pfizer Prod Inc | formas de dosagem fornecendo liberação controlada de inibidores de proteìna de transferência de ésteres de colesterila e liberação imediata de inibidores de hmg-coa redutase |
| 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 |
| BRPI0816382A2 (pt) | 2007-09-06 | 2015-02-24 | Merck Sharp & Dohme | Composto, composição, e, métodos para ativar a guanilato ciclase solúvel e para tratar ou previnir doenças |
| WO2009094242A1 (en) | 2008-01-24 | 2009-07-30 | Merck & Co., Inc. | Angiotensin ii receptor antagonists |
| US8476430B2 (en) | 2008-07-24 | 2013-07-02 | Bristol-Myers Squibb Company | Fused heterocyclic compounds useful as kinase modulators |
| EP2350097A1 (en) * | 2008-10-02 | 2011-08-03 | Merck Frosst Canada Ltd. | Heteroaromatic compounds as inhibitors of stearoyl-coenzyme a delta-9 desaturase |
| AU2009322836B2 (en) | 2008-11-25 | 2013-04-04 | Merck Sharp & Dohme Corp. | Soluble guanylate cyclase activators |
| KR20110133034A (ko) | 2009-02-26 | 2011-12-09 | 머크 샤프 앤드 돔 코포레이션 | 가용성 구아닐레이트 시클라제 활성화제 |
| CN102770133A (zh) | 2010-02-05 | 2012-11-07 | 拜耳知识产权有限责任公司 | 用于治疗囊性纤维化的单独和与PDE5抑制剂组合的sGC刺激剂或sGC激活剂 |
| WO2011115804A1 (en) * | 2010-03-17 | 2011-09-22 | Ironwood Pharmaceuticals, Inc. | Sgc stimulators |
| US9284301B2 (en) | 2010-03-25 | 2016-03-15 | Merck Sharp & Dohme Corp. | Soluble guanylate cyclase activators |
| KR20140019004A (ko) | 2010-05-27 | 2014-02-13 | 머크 샤프 앤드 돔 코포레이션 | 가용성 구아닐레이트 시클라제 활성화제 |
| EP2579717A4 (en) * | 2010-06-09 | 2013-12-11 | Merck Sharp & Dohme | POSITIVE ALLOSTERIC MODULATORS OF MGLUR2 |
| 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 |
| CN107266433A (zh) | 2010-11-09 | 2017-10-20 | 铁木医药有限公司 | sGC刺激剂 |
| KR101719556B1 (ko) | 2011-03-30 | 2017-03-24 | 주식회사 레고켐 바이오사이언스 | 신규한 세파로스포린 유도체 및 이를 함유하는 의약 조성물 |
| CN104039784B (zh) | 2011-09-02 | 2017-08-22 | 拜耳知识产权有限责任公司 | 取代的增环嘧啶及其用途 |
| DE102012200352A1 (de) | 2012-01-11 | 2013-07-11 | Bayer Intellectual Property Gmbh | Substituierte, annellierte Imidazole und Pyrazole und ihre Verwendung |
| WO2013131923A1 (de) | 2012-03-06 | 2013-09-12 | Bayer Intellectual Property Gmbh | Substituierte azabicyclen und ihre verwendung |
| WO2014047111A1 (en) * | 2012-09-18 | 2014-03-27 | Ironwood Pharmaceuticals, Inc. | Sgc stimulators |
| EP2897953B8 (en) | 2012-09-19 | 2019-06-26 | Cyclerion Therapeutics, Inc. | Sgc stimulators |
| WO2014060112A1 (en) * | 2012-10-19 | 2014-04-24 | Origenis Gmbh | Pyrazolo[4,3-d]pyrimidines as kinase inhibitors |
| CA2894126A1 (en) | 2012-12-21 | 2014-06-26 | Epizyme, Inc. | Prmt5 inhibitors and uses thereof |
| EA033168B1 (ru) | 2013-03-15 | 2019-09-30 | Сайклерион Терапьютикс, Инк. | СТИМУЛЯТОРЫ sGC |
| AU2014305843B2 (en) * | 2013-08-09 | 2019-08-29 | Ardelyx, Inc. | Compounds and methods for inhibiting phosphate transport |
| CA2933250A1 (en) * | 2013-12-11 | 2015-06-18 | 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 |
| US20170298055A1 (en) * | 2014-09-17 | 2017-10-19 | Ironwood Pharmaceuticals, Inc. | sGC STIMULATORS |
| EA201790627A1 (ru) * | 2014-09-17 | 2017-09-29 | Айронвуд Фармасьютикалз, Инк. | СТИМУЛЯТОРЫ рГЦ |
| EP3194382B1 (en) * | 2014-09-17 | 2021-09-08 | Cyclerion Therapeutics, Inc. | Pyrazole derivatives as sgc stimulators |
| US20180344735A1 (en) * | 2015-12-14 | 2018-12-06 | Ironwood Pharmaceuticals, Inc. | USE OF sGC STIMULATORS FOR THE TREATMENT OF GASTROINTESTINAL SPHINCTER DYSFUNCTION |
| AU2017216429B2 (en) * | 2016-02-01 | 2022-10-06 | Cyclerion Therapeutics, Inc. | Use of sGC stimulators for the treatment of Nonalcoholic Steatohepatitis (NASH) |
| SI3507291T1 (sl) * | 2016-09-02 | 2021-11-30 | Cyclerion Therapeutics, Inc. | Kondenzirani biciklični SGS stimulatorji |
| EP3554488A2 (en) * | 2016-12-13 | 2019-10-23 | Cyclerion Therapeutics, Inc. | Use of sgc stimulators for the treatment of esophageal motility disorders |
-
2015
- 2015-09-16 EP EP15778428.1A patent/EP3194386A2/en not_active Withdrawn
- 2015-09-16 US US15/511,888 patent/US10844064B2/en not_active Expired - Fee Related
- 2015-09-16 JP JP2017515197A patent/JP2017527604A/ja not_active Withdrawn
- 2015-09-16 CN CN201580062197.4A patent/CN107406421A/zh active Pending
- 2015-09-16 MX MX2017003518A patent/MX2017003518A/es unknown
- 2015-09-16 CA CA2961489A patent/CA2961489A1/en not_active Abandoned
- 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
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2012003405A1 (en) * | 2010-06-30 | 2012-01-05 | Ironwood Pharmaceuticals, Inc. | Sgc stimulators |
| WO2013101830A1 (en) * | 2011-12-27 | 2013-07-04 | Ironwood Pharmaceuticals, Inc. | 2 - benzyl, 3 - (pyrimidin- 2 -yl) substituted pyrazoles useful as sgc stimulators |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111836811A (zh) * | 2018-03-07 | 2020-10-27 | 塞科里昂医疗股份有限公司 | 制备可溶性鸟苷酸环化酶刺激剂的方法 |
| CN111836811B (zh) * | 2018-03-07 | 2024-11-22 | 帝善多制药公司 | 制备可溶性鸟苷酸环化酶刺激剂的方法 |
| CN111423377A (zh) * | 2020-05-12 | 2020-07-17 | 中国药科大学 | 5-氨基-1h-吡唑衍生物、制备方法及医药用途 |
| 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 |
| 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 |
Also Published As
| Publication number | Publication date |
|---|---|
| MX2017003518A (es) | 2017-07-28 |
| CA2961489A1 (en) | 2016-03-24 |
| IL251113A0 (en) | 2017-04-30 |
| US20180155345A1 (en) | 2018-06-07 |
| JP2017527604A (ja) | 2017-09-21 |
| EP3194386A2 (en) | 2017-07-26 |
| WO2016044446A3 (en) | 2016-06-16 |
| US10844064B2 (en) | 2020-11-24 |
| WO2016044446A2 (en) | 2016-03-24 |
| AU2015317823A1 (en) | 2017-03-23 |
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