ES2694297T3 - Formas cristalinas de ácido {[1-ciano-5-(4-clorofenoxi)-4-hidroxi-isoquinolina-3-carbonilo]-amino}-acético - Google Patents
Formas cristalinas de ácido {[1-ciano-5-(4-clorofenoxi)-4-hidroxi-isoquinolina-3-carbonilo]-amino}-acético Download PDFInfo
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- ES2694297T3 ES2694297T3 ES14704030.7T ES14704030T ES2694297T3 ES 2694297 T3 ES2694297 T3 ES 2694297T3 ES 14704030 T ES14704030 T ES 14704030T ES 2694297 T3 ES2694297 T3 ES 2694297T3
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- C—CHEMISTRY; METALLURGY
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/22—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems 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 carbon atoms of the nitrogen-containing ring
- C07D217/26—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
-
- 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
- A61K31/47—Quinolines; Isoquinolines
- A61K31/472—Non-condensed isoquinolines, e.g. papaverine
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/06—Antianaemics
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Epidemiology (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201361756361P | 2013-01-24 | 2013-01-24 | |
| US201361756361P | 2013-01-24 | ||
| PCT/US2014/012780 WO2014116849A1 (en) | 2013-01-24 | 2014-01-23 | Crystalline forms of {[1-cyano-5-(4-chlorophenoxy)-4-hydroxy-isoquinoline-3-carbonyl]-amino}-acetic acid |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2694297T3 true ES2694297T3 (es) | 2018-12-19 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
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Country Status (15)
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| US (1) | US9643928B2 (enExample) |
| EP (1) | EP2951159B1 (enExample) |
| JP (1) | JP6437456B2 (enExample) |
| KR (1) | KR102233081B1 (enExample) |
| CN (1) | CN105452227B (enExample) |
| AU (1) | AU2014209319B2 (enExample) |
| CA (1) | CA2899024C (enExample) |
| DK (1) | DK2951159T3 (enExample) |
| ES (1) | ES2694297T3 (enExample) |
| IL (1) | IL240066B (enExample) |
| MX (1) | MX360048B (enExample) |
| RU (1) | RU2666144C2 (enExample) |
| SG (2) | SG10202009266PA (enExample) |
| TW (1) | TWI685487B (enExample) |
| WO (1) | WO2014116849A1 (enExample) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103145616B (zh) | 2003-06-06 | 2015-09-30 | 菲布罗根有限公司 | 含氮杂芳基化合物及其在增加内源性促红细胞生成素中的用途 |
| WO2010056767A1 (en) | 2008-11-14 | 2010-05-20 | Fibrogen, Inc. | Thiochromene derivatives as hip hydroxylase inhibitors |
| EP3470397B1 (en) | 2012-07-16 | 2021-12-29 | Fibrogen, Inc. | Crystalline forms of a prolyl hydroxylase inhibitor |
| US8883823B2 (en) | 2012-07-16 | 2014-11-11 | Fibrogen, Inc. | Crystalline forms of a prolyl hydroxylase inhibitor |
| SG11201500234YA (en) | 2012-07-16 | 2015-02-27 | Fibrogen Inc | Process for making isoquinoline compounds |
| SG10202009266PA (en) | 2013-01-24 | 2020-10-29 | Fibrogen Inc | Crystalline forms of {[1-cyano-5-(4-chlorophenoxy)-4-hydroxy-isoquinoline-3-carbonyl]-amino}-acetic acid |
| IL296484B2 (en) | 2013-06-06 | 2025-03-01 | Fibrogen Inc | Pharmaceutical formulations of HIF hydroxylase inhibitor |
| CA2959688C (en) | 2014-09-02 | 2024-02-27 | Sunshine Lake Pharma Co., Ltd. | Quinolone compounds and their use to treat diseases related to hypoxia inducible factor and/or erythropoietin |
| EP4121009A4 (en) * | 2020-03-17 | 2024-04-17 | Zydus Lifesciences Limited | Formulation comprising hif prolyl hydroxylase inhibitors |
| WO2021216530A1 (en) | 2020-04-20 | 2021-10-28 | Akebia Therapeutics, Inc. | Treatment of viral infections, of organ injury, and of related conditions using a hif prolyl hydroxylase inhibitor or a hif-alpha stabilizer |
Family Cites Families (57)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4036964A (en) | 1973-10-11 | 1977-07-19 | Beecham Group Limited | Isocarbostyril-3-carboxylic acid derivatives for the prophylaxis of asthma, hayfever and rhinitis |
| US3989704A (en) | 1973-10-30 | 1976-11-02 | Sandoz, Inc. | 3-Substituted-4-aryl isoquinolines |
| DE2818423A1 (de) | 1978-04-27 | 1979-11-08 | Hoechst Ag | Neue isochinolinderivate und verfahren zu ihrer herstellung |
| DE3233424A1 (de) | 1982-09-09 | 1984-03-15 | Hoechst Ag, 6230 Frankfurt | Isochinolinderivate, verfahren zu ihrer herstellung, pharmazeutische praeparate auf basis dieser verbindungen und ihre verwendung |
| US4559403A (en) | 1983-05-19 | 1985-12-17 | Hoffmann-La Roche Inc. | Substituted isoquinolines |
| US4584379A (en) | 1985-01-22 | 1986-04-22 | Merrell Dow Pharmaceuticals Inc. | Isoquinoline thromboxane synthetase inhibitors |
| US4822800A (en) | 1986-06-09 | 1989-04-18 | Ortho Pharmaceutical Corporation | Isoquinolinol compounds having cardiotonic and phosphodiesterase fraction III inhibiting properties and/or renal vasodilating properties |
| US4966906A (en) | 1987-11-27 | 1990-10-30 | Hoechst-Roussel Pharmaceuticals Inc. | 1-aryl-3-isoquinolinecarboxamides |
| US4952588A (en) | 1987-11-27 | 1990-08-28 | Hoechst-Roussel Pharmaceuticals Inc. | 1-aryl-3-quinoline-and 1-aryl-3-isoquinoline-carboxamides |
| EP0532466A3 (en) | 1991-09-12 | 1993-06-16 | Ciba-Geigy Ag | Derivatives of 5-amino-4-hydroxy-hexanoic acid and their therapeutical use |
| EP0626178A1 (de) | 1993-05-17 | 1994-11-30 | Ciba-Geigy Ag | Verwendung von Hemmstoffen von HIV-Aspartatproteasen zur Bekämpfung von Tumorerkrankungen |
| ATE149485T1 (de) | 1993-11-02 | 1997-03-15 | Hoechst Ag | Substituierte heterocyclische carbonsäureamidester, ihre herstellung und ihre verwendung als arzneimittel |
| EP0650961B1 (de) | 1993-11-02 | 1997-03-05 | Hoechst Aktiengesellschaft | Substituierte heterocyclische Carbonsäureamide, ihre Herstellung und ihre Verwendung als Arzneimittel |
| CA2138929A1 (en) | 1993-12-30 | 1995-07-01 | Klaus Weidmann | Substituted heterocyclic carboxamides, their preparation and their use as pharmaceuticals |
| US5563143A (en) | 1994-09-21 | 1996-10-08 | Pfizer Inc. | Catechol diether compounds as inhibitors of TNF release |
| AU4515696A (en) | 1994-12-12 | 1996-07-03 | Merck & Co., Inc. | Substituted 2-aminopyridines as inhibitors of nitric oxide synthase |
| IL135495A (en) | 1995-09-28 | 2002-12-01 | Hoechst Ag | Intermediate compounds for the preparation of quinoline-converted amines - 2 - carboxylic acid |
| PT944619E (pt) | 1996-11-27 | 2007-01-31 | Bristol Myers Squibb Pharma Co | Novos antagonistas dos receptores da integrina |
| GB9707830D0 (en) | 1997-04-18 | 1997-06-04 | Smithkline Beecham Plc | Novel compounds |
| WO1998050346A2 (en) | 1997-04-18 | 1998-11-12 | Smithkline Beecham Plc | Acetamide and urea derivatives, process for their preparation and their use in the treatment of cns disorders |
| DE19746287A1 (de) | 1997-10-20 | 1999-04-22 | Hoechst Marion Roussel De Gmbh | Substituierte Isochinolin-2-Carbonsäureamide, ihre Herstellung und ihre Verwendung als Arzneimittel |
| FR2779963A1 (fr) | 1998-06-22 | 1999-12-24 | Centre Nat Rech Scient | Utilisation d'un compose possedant une affinite pour le recepteur mitochondrial des benzodiazepines en therapie du cancer |
| IT1302677B1 (it) | 1998-10-15 | 2000-09-29 | Zambon Spa | Derivati benzazinici inibitori della fosfodiesterasi 4 |
| WO2000064877A1 (en) | 1999-04-26 | 2000-11-02 | Neurogen Corporation | 2-aminoquinolinecarboxamides: neurokinin receptor ligands |
| IT1320162B1 (it) | 2000-02-09 | 2003-11-18 | Rotta Research Lab | Derivati della tirosina ad attivita' anti leucotrienica, procedimentoper la loro preparazione e loro uso farmaceutico. |
| US7622503B2 (en) | 2000-08-24 | 2009-11-24 | University Of Tennessee Research Foundation | Selective androgen receptor modulators and methods of use thereof |
| FI20002044A0 (fi) | 2000-09-15 | 2000-09-15 | Orion Yhtymae Oyj | Comt-entsyymiä estäviä naftaleenijohdannaisia |
| DE10110750A1 (de) | 2001-03-07 | 2002-09-12 | Bayer Ag | Neuartige Aminodicarbonsäurederivate mit pharmazeutischen Eigenschaften |
| JP4590157B2 (ja) | 2001-03-21 | 2010-12-01 | アイシス イノヴェイション リミテッド | アッセイ、方法および手段 |
| US6716866B2 (en) | 2001-06-13 | 2004-04-06 | Genesoft Pharmaceuticals, Inc. | Aryl-benzimidazole compounds having antiinfective activity |
| CA2450625A1 (en) | 2001-06-13 | 2002-12-19 | Genesoft Pharmaceuticals, Inc. | Isoquinoline compounds having antiinfective activity |
| CA2448737C (en) | 2001-07-20 | 2010-06-01 | Boehringer Ingelheim (Canada) Ltd. | Viral polymerase inhibitors |
| EP2335700A1 (en) | 2001-07-25 | 2011-06-22 | Boehringer Ingelheim (Canada) Ltd. | Hepatitis C virus polymerase inhibitors with a heterobicylic structure |
| US7294457B2 (en) | 2001-08-07 | 2007-11-13 | Boehringer Ingelheim (Canada) Ltd. | Direct binding assay for identifying inhibitors of HCV polymerase |
| US6762318B2 (en) | 2001-12-03 | 2004-07-13 | Novo Nordisk A/S | Glucagon antagonists |
| HU229475B1 (en) | 2001-12-06 | 2014-01-28 | Fibrogen | Methods of increasing endogenous erythropoietin (epo) |
| GB0206711D0 (en) | 2002-03-21 | 2002-05-01 | Isis Innovation | HIF Inhibitor |
| US8124582B2 (en) | 2002-12-06 | 2012-02-28 | Fibrogen, Inc. | Treatment of diabetes |
| US7618940B2 (en) | 2002-12-06 | 2009-11-17 | Fibrogen, Inc. | Fat regulation |
| WO2005007192A2 (en) | 2003-06-06 | 2005-01-27 | Fibrogen, Inc. | Cytoprotection through the use of hif hydroxylase inhibitors |
| CN103145616B (zh) | 2003-06-06 | 2015-09-30 | 菲布罗根有限公司 | 含氮杂芳基化合物及其在增加内源性促红细胞生成素中的用途 |
| US8614204B2 (en) | 2003-06-06 | 2013-12-24 | Fibrogen, Inc. | Enhanced erythropoiesis and iron metabolism |
| EP1646611A1 (en) | 2003-07-15 | 2006-04-19 | Merck & Co., Inc. | Hydroxypyridine cgrp receptor antagonists |
| US7544699B2 (en) | 2003-08-08 | 2009-06-09 | Transtech Pharma, Inc. | Aryl and heteroaryl compounds, compositions, and methods of use |
| US7208601B2 (en) | 2003-08-08 | 2007-04-24 | Mjalli Adnan M M | Aryl and heteroaryl compounds, compositions, and methods of use |
| WO2006020133A2 (en) | 2004-07-15 | 2006-02-23 | Powerprecise Solutions, Inc. | One time operating state detecting method and apparatus |
| EP1676834A1 (en) | 2004-12-30 | 2006-07-05 | Sanofi-Aventis Deutschland GmbH | Fused bicyclic carboxamide derivates for use as CXCR2 inhibitors in the treatment of inflammation |
| US8703795B2 (en) | 2005-03-02 | 2014-04-22 | Fibrogen, Inc. | Thienopyridine compounds, and methods of use thereof |
| CN101849943A (zh) | 2005-06-06 | 2010-10-06 | 菲布罗根公司 | 使用HIFα稳定剂的改进的贫血治疗 |
| AU2006259352A1 (en) | 2005-06-15 | 2006-12-28 | Fibrogen, Inc. | Use of HIF 1alfa modulators for treatment of cancer |
| CN102351791B (zh) * | 2006-01-27 | 2014-10-29 | 菲布罗根有限公司 | 使低氧诱导因子(hif)稳定的氰基异喹啉化合物 |
| US20070259960A1 (en) | 2006-02-16 | 2007-11-08 | Fibrogen, Inc. | Compounds and methods for treatment of stroke |
| AU2007234408B2 (en) | 2006-04-04 | 2011-05-19 | Fibrogen, Inc. | Pyrrolo- and thiazolo-pyridine compounds as HIF modulators |
| US20070293575A1 (en) | 2006-06-15 | 2007-12-20 | Fibrogen, Inc. | Compounds and methods for treatment of cancer-related anemia |
| US7713986B2 (en) | 2006-06-15 | 2010-05-11 | Fibrogen, Inc. | Compounds and methods for treatment of chemotherapy-induced anemia |
| EP2231156A1 (en) | 2007-12-07 | 2010-09-29 | Fibrogen, Inc. | Methods for increasing white blood cells |
| SG10202009266PA (en) | 2013-01-24 | 2020-10-29 | Fibrogen Inc | Crystalline forms of {[1-cyano-5-(4-chlorophenoxy)-4-hydroxy-isoquinoline-3-carbonyl]-amino}-acetic acid |
-
2014
- 2014-01-23 SG SG10202009266PA patent/SG10202009266PA/en unknown
- 2014-01-23 SG SG11201505748UA patent/SG11201505748UA/en unknown
- 2014-01-23 JP JP2015555276A patent/JP6437456B2/ja not_active Expired - Fee Related
- 2014-01-23 EP EP14704030.7A patent/EP2951159B1/en active Active
- 2014-01-23 US US14/763,127 patent/US9643928B2/en not_active Expired - Fee Related
- 2014-01-23 DK DK14704030.7T patent/DK2951159T3/en active
- 2014-01-23 WO PCT/US2014/012780 patent/WO2014116849A1/en not_active Ceased
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- 2014-01-23 RU RU2015134420A patent/RU2666144C2/ru active
- 2014-01-23 KR KR1020157022614A patent/KR102233081B1/ko not_active Expired - Fee Related
- 2014-01-23 CN CN201480016402.9A patent/CN105452227B/zh not_active Expired - Fee Related
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- 2014-01-23 ES ES14704030.7T patent/ES2694297T3/es active Active
- 2014-01-23 TW TW103102462A patent/TWI685487B/zh not_active IP Right Cessation
- 2014-01-23 CA CA2899024A patent/CA2899024C/en active Active
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2015
- 2015-07-21 IL IL240066A patent/IL240066B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| KR20150129679A (ko) | 2015-11-20 |
| TWI685487B (zh) | 2020-02-21 |
| CA2899024A1 (en) | 2014-07-31 |
| WO2014116849A1 (en) | 2014-07-31 |
| JP2016505071A (ja) | 2016-02-18 |
| RU2666144C2 (ru) | 2018-09-06 |
| EP2951159A1 (en) | 2015-12-09 |
| SG11201505748UA (en) | 2015-08-28 |
| KR102233081B1 (ko) | 2021-03-29 |
| DK2951159T3 (en) | 2018-11-19 |
| HK1217331A1 (en) | 2017-01-06 |
| MX360048B (es) | 2018-10-19 |
| CA2899024C (en) | 2022-01-04 |
| CN105452227A (zh) | 2016-03-30 |
| US20160002170A1 (en) | 2016-01-07 |
| AU2014209319B2 (en) | 2018-04-19 |
| US9643928B2 (en) | 2017-05-09 |
| MX2015009617A (es) | 2016-04-20 |
| SG10202009266PA (en) | 2020-10-29 |
| JP6437456B2 (ja) | 2018-12-12 |
| TW201444800A (zh) | 2014-12-01 |
| EP2951159B1 (en) | 2018-08-22 |
| AU2014209319A1 (en) | 2015-08-27 |
| IL240066A0 (en) | 2015-09-24 |
| IL240066B (en) | 2019-08-29 |
| RU2015134420A (ru) | 2017-03-03 |
| CN105452227B (zh) | 2018-05-29 |
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