DE60124302T2 - Thiazolderivate zur behandlung von ppar-lierte krankheiten - Google Patents
Thiazolderivate zur behandlung von ppar-lierte krankheiten Download PDFInfo
- Publication number
- DE60124302T2 DE60124302T2 DE60124302T DE60124302T DE60124302T2 DE 60124302 T2 DE60124302 T2 DE 60124302T2 DE 60124302 T DE60124302 T DE 60124302T DE 60124302 T DE60124302 T DE 60124302T DE 60124302 T2 DE60124302 T2 DE 60124302T2
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- Germany
- Prior art keywords
- methyl
- mmol
- thiazol
- phenoxy
- propionic acid
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/22—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D277/24—Radicals substituted by oxygen atoms
-
- 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
-
- 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
-
- 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
- A61P3/04—Anorexiants; Antiobesity agents
-
- 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
- A61P3/06—Antihyperlipidemics
-
- 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
-
- 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
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- 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
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/22—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D277/26—Radicals substituted by sulfur atoms
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Diabetes (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
- Hospice & Palliative Care (AREA)
- Urology & Nephrology (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Child & Adolescent Psychology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0031107 | 2000-12-20 | ||
| GBGB0031107.6A GB0031107D0 (en) | 2000-12-20 | 2000-12-20 | Chemical compounds |
| PCT/US2001/049230 WO2002062774A1 (en) | 2000-12-20 | 2001-12-19 | Thiazole derivatives for treating ppar related disorders |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE60124302D1 DE60124302D1 (de) | 2006-12-14 |
| DE60124302T2 true DE60124302T2 (de) | 2007-05-03 |
Family
ID=9905492
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE60124302T Expired - Fee Related DE60124302T2 (de) | 2000-12-20 | 2001-12-19 | Thiazolderivate zur behandlung von ppar-lierte krankheiten |
Country Status (27)
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|---|---|
| EP (1) | EP1343773B1 (enExample) |
| JP (1) | JP4209681B2 (enExample) |
| KR (1) | KR100815022B1 (enExample) |
| CN (1) | CN1252057C (enExample) |
| AR (1) | AR035522A1 (enExample) |
| AT (1) | ATE344253T1 (enExample) |
| AU (1) | AU2002246713B2 (enExample) |
| BR (1) | BR0116370A (enExample) |
| CA (1) | CA2432188A1 (enExample) |
| CY (1) | CY1105915T1 (enExample) |
| CZ (1) | CZ20031737A3 (enExample) |
| DE (1) | DE60124302T2 (enExample) |
| DK (1) | DK1343773T3 (enExample) |
| ES (1) | ES2274914T3 (enExample) |
| GB (1) | GB0031107D0 (enExample) |
| HU (1) | HUP0400837A3 (enExample) |
| IL (2) | IL156436A0 (enExample) |
| MX (1) | MXPA03005699A (enExample) |
| MY (1) | MY136685A (enExample) |
| NO (1) | NO20032801L (enExample) |
| NZ (1) | NZ526543A (enExample) |
| PL (1) | PL365797A1 (enExample) |
| PT (1) | PT1343773E (enExample) |
| SI (1) | SI1343773T1 (enExample) |
| TW (1) | TWI292759B (enExample) |
| WO (1) | WO2002062774A1 (enExample) |
| ZA (1) | ZA200304679B (enExample) |
Families Citing this family (46)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7041691B1 (en) | 1999-06-30 | 2006-05-09 | Amgen Inc. | Compounds for the modulation of PPARγ activity |
| IL152979A0 (en) | 2000-05-26 | 2003-06-24 | Nippon Shinyaku Co Ltd | Heterocyclic compounds |
| US20030171399A1 (en) | 2000-06-28 | 2003-09-11 | Tularik Inc. | Quinolinyl and benzothiazolyl modulators |
| GB0031109D0 (en) | 2000-12-20 | 2001-01-31 | Glaxo Group Ltd | Chemical compounds |
| US20040072838A1 (en) | 2000-12-20 | 2004-04-15 | Pierette Banker | Thiazole and oxazole derivatives as activators of human peroxisome proliferator activated receptors |
| HRP20040098B1 (en) * | 2001-08-13 | 2012-08-31 | Janssen Pharmaceutica N.V. | 2,4,5-TRlSUBSTITUTED THIAZOLYL DERIVATIVES AND THEIR ANTIINFLAMMATORY ACTIVITY |
| WO2003072100A1 (en) * | 2002-02-25 | 2003-09-04 | Eli Lilly And Company | Peroxisome proliferator activated receptor modulators |
| US7259175B2 (en) | 2002-02-25 | 2007-08-21 | Eli Lilly And Company | Peroxisome proliferator activated receptor modulators |
| US20030207924A1 (en) * | 2002-03-07 | 2003-11-06 | Xue-Min Cheng | Compounds that modulate PPAR activity and methods of preparation |
| US6833380B2 (en) | 2002-03-07 | 2004-12-21 | Warner-Lambert Company, Llc | Compounds that modulate PPAR activity and methods of preparation |
| US6875780B2 (en) | 2002-04-05 | 2005-04-05 | Warner-Lambert Company | Compounds that modulate PPAR activity and methods for their preparation |
| US7244763B2 (en) | 2003-04-17 | 2007-07-17 | Warner Lambert Company Llc | Compounds that modulate PPAR activity and methods of preparation |
| US6987118B2 (en) * | 2003-05-21 | 2006-01-17 | Pfizer Inc. | Tetrahydroisoquinoline derivatives as PPAR-alpha activators |
| AU2004247355A1 (en) | 2003-06-06 | 2004-12-23 | F. Hoffmann-La Roche Ag | Aniline derivatives |
| BRPI0412236A (pt) | 2003-07-02 | 2006-09-12 | Hoffmann La Roche | compostos, processo para a sua manufatura, composições farmacêuticas que compreendem os mesmos, método para o tratamento e/ou prevenção de enfermidades que são moduladas por agonistas ppar(delta) e/ou ppar(alfa), e utilização desses compostos |
| UA87467C2 (xx) | 2003-09-19 | 2009-07-27 | Янссен Фармацевтика Н.В | 4-((феноксіалкіл)тіо)феноксіоцтова кислота та її аналоги$4-((феноксиалкил)тио)феноксиуксусная кислота и ее аналоги |
| US7223761B2 (en) | 2003-10-03 | 2007-05-29 | Amgen Inc. | Salts and polymorphs of a potent antidiabetic compound |
| EP1737809B1 (en) * | 2004-02-27 | 2013-09-18 | Amgen, Inc | Compounds, pharmaceutical compositions and methods for use in treating metabolic disorders |
| ES2352085T3 (es) | 2004-05-05 | 2011-02-15 | High Point Pharmaceuticals, Llc | Nuevos compuestos, su preparación y uso. |
| WO2005105736A1 (en) | 2004-05-05 | 2005-11-10 | Novo Nordisk A/S | Novel compounds, their preparation and use |
| MY145712A (en) * | 2004-09-15 | 2012-03-30 | Janssen Pharmaceutica Nv | 4-((phenoxyalkyl)thio)-phenoxyacetic acids and analogs |
| MY147518A (en) * | 2004-09-15 | 2012-12-31 | Janssen Pharmaceutica Nv | 4-((phenoxyalkyl)thio)-phenoxyacetic acids and analogs |
| WO2006071103A1 (en) * | 2004-12-31 | 2006-07-06 | Heonjoong Kang | Organoselenium containing compounds and their use |
| EP1856072A4 (en) * | 2005-02-25 | 2009-10-21 | Seoul Nat Univ Ind Foundation | THIAZOLE DERIVATIVES AS PPAR DELTA LIGANDS AND PROCESSES FOR THE PRODUCTION THEREOF |
| JP5191744B2 (ja) * | 2005-02-25 | 2013-05-08 | ソウル ナショナル ユニバーシティー インダストリー ファンデーション | ペルオキシソーム増殖子活性化受容体デルタリガンドのチアゾール誘導体及びその製造方法 |
| US7465804B2 (en) | 2005-05-20 | 2008-12-16 | Amgen Inc. | Compounds, pharmaceutical compositions and methods for their use in treating metabolic disorders |
| ES2372617T3 (es) | 2005-06-30 | 2012-01-24 | High Point Pharmaceuticals, Llc | Ácidos fenoxiacéticos como activadores de ppar-delta. |
| US7582803B2 (en) | 2005-09-14 | 2009-09-01 | Amgen Inc. | Conformationally constrained 3-(4-hydroxy-phenyl)-substituted-propanoic acids useful for treating metabolic disorders |
| JO3006B1 (ar) | 2005-09-14 | 2016-09-05 | Janssen Pharmaceutica Nv | املاح ليسين مبتكرة من مشتقات حامض 4-((فينوكسي الكيل)ثيو) فينوكسي الخليك |
| EA201101085A1 (ru) | 2005-12-22 | 2012-05-30 | ХАЙ ПОЙНТ ФАРМАСЬЮТИКАЛЗ, ЭлЭлСи | Феноксиуксусные кислоты в качестве активаторов ppar дельта |
| CN101007790B (zh) * | 2006-01-27 | 2011-03-30 | 北京摩力克科技有限公司 | 草氨酸衍生物、其制备方法和医药用途 |
| EP1999098A2 (en) | 2006-03-09 | 2008-12-10 | High Point Pharmaceuticals, LLC | Compounds that modulate ppar activity, their preparation and use |
| PE20080188A1 (es) * | 2006-04-18 | 2008-03-10 | Janssen Pharmaceutica Nv | Derivados del acido benzoazepin-oxi-acetico como agonistas de ppar-delta usados para aumentar hdl-c, reducir ldl-c y reducir colesterol |
| EP2061760A1 (en) | 2006-09-07 | 2009-05-27 | Amgen, Inc | Benzo-fused compounds for use in treating metabolic disorders |
| CA2662305C (en) | 2006-09-07 | 2012-04-17 | Amgen Inc. | Heterocyclic gpr40 modulators |
| US8519145B2 (en) | 2006-12-02 | 2013-08-27 | Seoul National University Industry Foundation | Aryl compounds as PPAR ligands and their use |
| BRPI0807023A2 (pt) * | 2007-01-08 | 2014-04-22 | Seoul Nat Univ Ind Foundation | Composto de tiazol como ligante de ppard e produto farmacêutico, cosmético e alimento saudável dele composto |
| PE20090159A1 (es) | 2007-03-08 | 2009-02-21 | Plexxikon Inc | COMPUESTOS DERIVADOS DE ACIDO INDOL-PROPIONICO COMO MODULADORES PPARs |
| ES2446419T3 (es) | 2007-04-16 | 2014-03-07 | Amgen, Inc | Moduladores de GPR40 de ácidos bifenilfenoxi, tiofenil y aminofenilpropanoico sustituidos |
| JP5591706B2 (ja) | 2007-10-10 | 2014-09-17 | アムジエン・インコーポレーテツド | 置換ビフェニルｇｐｒ４０調節因子 |
| WO2009111056A1 (en) | 2008-03-06 | 2009-09-11 | Amgen Inc. | Conformationally constrained carboxylic acid derivatives useful for treating metabolic disorders |
| AU2009303475B2 (en) | 2008-10-15 | 2012-09-13 | Amgen Inc. | Spirocyclic GPR40 modulators |
| CN102781924A (zh) * | 2010-02-25 | 2012-11-14 | 首尔大学校产学协力财团 | 用作过氧化物酶体增殖剂激活受体的配体的硒唑衍生物、其制备方法及其化合物的用途 |
| US20120094959A1 (en) | 2010-10-19 | 2012-04-19 | Bonnie Blazer-Yost | Treatment of cystic diseases |
| WO2015035171A1 (en) | 2013-09-09 | 2015-03-12 | High Point Pharmaceuticals, Llc | Use of a ppar-delta agonist for treating muscle atrophy |
| WO2023147309A1 (en) | 2022-01-25 | 2023-08-03 | Reneo Pharmaceuticals, Inc. | Use of ppar-delta agonists in the treatment of disease |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4434164A (en) * | 1981-06-01 | 1984-02-28 | Pfizer Inc. | Crystalline benzothiazine dioxide salts |
| US4623486A (en) * | 1985-05-29 | 1986-11-18 | Pfizer Inc. | [4-substituted benzoyloxy]-N-substituted-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxides having anti-arthritic activity |
| GB9914977D0 (en) * | 1999-06-25 | 1999-08-25 | Glaxo Group Ltd | Chemical compounds |
| PE20011010A1 (es) * | 1999-12-02 | 2001-10-18 | Glaxo Group Ltd | Oxazoles y tiazoles sustituidos como agonista del receptor activado por el proliferador de peroxisomas humano |
-
2000
- 2000-12-20 GB GBGB0031107.6A patent/GB0031107D0/en not_active Ceased
-
2001
- 2001-12-18 TW TW090131348A patent/TWI292759B/zh active
- 2001-12-18 AR ARP010105863A patent/AR035522A1/es not_active Application Discontinuation
- 2001-12-19 KR KR1020037008392A patent/KR100815022B1/ko not_active Expired - Fee Related
- 2001-12-19 BR BR0116370-1A patent/BR0116370A/pt not_active IP Right Cessation
- 2001-12-19 SI SI200130672T patent/SI1343773T1/sl unknown
- 2001-12-19 CZ CZ20031737A patent/CZ20031737A3/cs unknown
- 2001-12-19 DE DE60124302T patent/DE60124302T2/de not_active Expired - Fee Related
- 2001-12-19 AT AT01994305T patent/ATE344253T1/de not_active IP Right Cessation
- 2001-12-19 EP EP01994305A patent/EP1343773B1/en not_active Expired - Lifetime
- 2001-12-19 PL PL01365797A patent/PL365797A1/xx not_active Application Discontinuation
- 2001-12-19 MY MYPI20015760A patent/MY136685A/en unknown
- 2001-12-19 IL IL15643601A patent/IL156436A0/xx active IP Right Grant
- 2001-12-19 CA CA002432188A patent/CA2432188A1/en not_active Abandoned
- 2001-12-19 AU AU2002246713A patent/AU2002246713B2/en not_active Ceased
- 2001-12-19 WO PCT/US2001/049230 patent/WO2002062774A1/en not_active Ceased
- 2001-12-19 NZ NZ526543A patent/NZ526543A/en unknown
- 2001-12-19 DK DK01994305T patent/DK1343773T3/da active
- 2001-12-19 CN CNB018223095A patent/CN1252057C/zh not_active Expired - Fee Related
- 2001-12-19 HU HU0400837A patent/HUP0400837A3/hu unknown
- 2001-12-19 JP JP2002562729A patent/JP4209681B2/ja not_active Expired - Fee Related
- 2001-12-19 MX MXPA03005699A patent/MXPA03005699A/es active IP Right Grant
- 2001-12-19 PT PT01994305T patent/PT1343773E/pt unknown
- 2001-12-19 ES ES01994305T patent/ES2274914T3/es not_active Expired - Lifetime
-
2003
- 2003-06-12 IL IL156436A patent/IL156436A/en not_active IP Right Cessation
- 2003-06-17 ZA ZA200304679A patent/ZA200304679B/en unknown
- 2003-06-19 NO NO20032801A patent/NO20032801L/no not_active Application Discontinuation
-
2007
- 2007-01-10 CY CY20071100032T patent/CY1105915T1/el unknown
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