JP2012501334A - 置換アミノチアゾール誘導体、医薬組成物、および使用の方法 - Google Patents
置換アミノチアゾール誘導体、医薬組成物、および使用の方法 Download PDFInfo
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- JP2012501334A JP2012501334A JP2011525147A JP2011525147A JP2012501334A JP 2012501334 A JP2012501334 A JP 2012501334A JP 2011525147 A JP2011525147 A JP 2011525147A JP 2011525147 A JP2011525147 A JP 2011525147A JP 2012501334 A JP2012501334 A JP 2012501334A
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- FRFAQMKDIVZURC-UHFFFAOYSA-N 3-[[4-[4-(4-fluorophenyl)cyclohexyl]-1,3-thiazol-2-yl]-[(5-methylthiophen-2-yl)methyl]amino]propanoic acid Chemical compound S1C(C)=CC=C1CN(CCC(O)=O)C1=NC(C2CCC(CC2)C=2C=CC(F)=CC=2)=CS1 FRFAQMKDIVZURC-UHFFFAOYSA-N 0.000 claims description 2
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- ZRZZQCNAIDQHNS-UHFFFAOYSA-N 3-[[4-(4,4-dimethylcyclohexyl)-1,3-thiazol-2-yl]-[(5-methylthiophen-2-yl)methyl]amino]propanoic acid Chemical compound S1C(C)=CC=C1CN(CCC(O)=O)C1=NC(C2CCC(C)(C)CC2)=CS1 ZRZZQCNAIDQHNS-UHFFFAOYSA-N 0.000 claims 1
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- 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
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
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- A61P3/06—Antihyperlipidemics
-
- 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
- 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
- C07D417/02—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 two hetero rings
- C07D417/12—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 two hetero rings linked by a chain containing hetero atoms as chain links
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)
- Hematology (AREA)
- Diabetes (AREA)
- Obesity (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Epidemiology (AREA)
- Child & Adolescent Psychology (AREA)
- Gynecology & Obstetrics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US9284408P | 2008-08-29 | 2008-08-29 | |
| US61/092,844 | 2008-08-29 | ||
| PCT/US2009/054920 WO2010025142A1 (en) | 2008-08-29 | 2009-08-25 | Substituted aminothiazole derivatives, pharmaceutical compositions, and methods of use |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2012501334A true JP2012501334A (ja) | 2012-01-19 |
| JP2012501334A5 JP2012501334A5 (OSRAM) | 2012-05-17 |
Family
ID=41721863
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2011525147A Pending JP2012501334A (ja) | 2008-08-29 | 2009-08-25 | 置換アミノチアゾール誘導体、医薬組成物、および使用の方法 |
Country Status (5)
| Country | Link |
|---|---|
| US (1) | US8563742B2 (OSRAM) |
| EP (1) | EP2320738A4 (OSRAM) |
| JP (1) | JP2012501334A (OSRAM) |
| CA (1) | CA2731442A1 (OSRAM) |
| WO (1) | WO2010025142A1 (OSRAM) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| LT3539551T (lt) | 2011-12-29 | 2022-01-10 | Rhythm Pharmaceuticals, Inc. | Su melanokortino-4 receptoriumi susijusių sutrikimų gydymo būdas heterozigotiniuose nešiotojuose |
| PT3356386T (pt) | 2015-09-30 | 2024-05-17 | Rhythm Pharmaceuticals Inc | Método de tratamento de distúrbios associados à via do receptor da melanocortina-4 |
| EP3773897A1 (en) | 2018-04-06 | 2021-02-17 | Rhythm Pharmaceuticals, Inc. | Compositions for treating kidney disease |
| EP3846793B1 (en) * | 2018-09-07 | 2024-01-24 | PIC Therapeutics, Inc. | Eif4e inhibitors and uses thereof |
| WO2021178488A1 (en) | 2020-03-03 | 2021-09-10 | PIC Therapeutics, Inc. | Eif4e inhibitors and uses thereof |
| CN118103368A (zh) | 2021-08-25 | 2024-05-28 | 皮克医疗公司 | Eif4e抑制剂及其用途 |
| US12157732B2 (en) | 2021-08-25 | 2024-12-03 | PIC Therapeutics, Inc. | eIF4E inhibitors and uses thereof |
| CA3246019A1 (en) | 2022-01-07 | 2023-07-13 | V. Mane Fils | COOLING COMPOUNDS AND COMPOUNDS |
Family Cites Families (44)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2607369B2 (ja) | 1987-02-20 | 1997-05-07 | 興和株式会社 | 新規な複素環化合物 |
| US5502025A (en) | 1987-08-13 | 1996-03-26 | Monsanto Company | Safening herbicidal pyrazolylsulfonylureas |
| YU48319B (sh) | 1988-08-01 | 1998-05-15 | Monsanto Company | Bezbednosni herbicidni derivati benzoeve kiseline |
| US5201933A (en) | 1988-08-01 | 1993-04-13 | Monsanto Company | Safening herbicidal benzoic acid derivatives |
| FR2656610B1 (fr) | 1989-12-29 | 1992-05-07 | Sanofi Sa | Derives d'amino-2 phenyl-4 thiazole, leur procede de preparation et leur application therapeutique. |
| JPH0532662A (ja) | 1990-11-09 | 1993-02-09 | Nissan Chem Ind Ltd | 置換ピラゾール誘導体および農園芸用殺菌剤 |
| CA2396738C (en) | 1990-11-30 | 2006-08-29 | Masatoshi Chihiro | Thiazole derivatives as active superoxide radical inhibitors |
| DE4124942A1 (de) | 1991-07-27 | 1993-01-28 | Thomae Gmbh Dr K | 5-gliedrige heterocyclen, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel |
| EP0627423A4 (en) | 1992-01-22 | 1995-02-15 | Nissan Chemical Ind Ltd | SUBSTITUTED PYRAZOLE DERIVATIVES AND BACTERICIDES FOR AGRICULTURE AND GARDENING. |
| WO1993017681A1 (en) | 1992-03-02 | 1993-09-16 | Abbott Laboratories | Angiotensin ii receptor antagonists |
| US6310034B1 (en) | 1993-05-21 | 2001-10-30 | Ut-Battelle, Llc | Agouti polypeptide compositions |
| JPH07149745A (ja) | 1993-11-30 | 1995-06-13 | Hisamitsu Pharmaceut Co Inc | 新規な２−アミノチアゾール誘導体 |
| US5627131A (en) | 1995-01-09 | 1997-05-06 | Zeneca Limited | Herbicidal compositions of 4-benzoylisoxazole and antidotes therefor |
| US5766877A (en) | 1996-05-10 | 1998-06-16 | Amgen Inc. | Genes encoding art, an agouti-related transcript |
| WO1997047299A1 (en) | 1996-06-12 | 1997-12-18 | 3-Dimensional Pharmaceuticals, Inc. | Amidino and guanidino heterocyclic protease inhibitors |
| FR2754258B1 (fr) | 1996-10-08 | 1998-12-31 | Sanofi Sa | Derives d'aminothiazole, leur procede de preparation et les compositions pharmaceutiques les contenant |
| US6011048A (en) | 1997-01-28 | 2000-01-04 | Merck & Co., Inc. | Thiazole benzenesulfonamides as β3 agonists for treatment of diabetes and obesity |
| WO1999050295A2 (en) | 1998-03-30 | 1999-10-07 | Gryphon Sciences | Agouti-related protein analogs and methods of use |
| US6689873B1 (en) | 1998-04-29 | 2004-02-10 | Merck & Co., Inc. | Nucleic acid encoding rat agouti related protein |
| CN1308619A (zh) | 1998-05-12 | 2001-08-15 | 美国家用产品公司 | (2－酰氨基噻唑－4－基)乙酸衍生物 |
| EP1077958A1 (en) | 1998-05-12 | 2001-02-28 | American Home Products Corporation | Oxazole-aryl-carboxylic acids useful in the treatment of insulin resistance and hyperglycemia |
| US6699896B1 (en) | 1998-05-12 | 2004-03-02 | Wyeth | Oxazole-aryl-carboxylic acids useful in the treatment of insulin resistance and hyperglycemia |
| GB9818666D0 (en) | 1998-08-27 | 1998-10-21 | Rhone Poulenc Agriculture | New herbicidal method |
| US6303749B1 (en) | 1999-01-29 | 2001-10-16 | Amgen Inc. | Agouti and agouti-related peptide analogs |
| EP1169038B9 (en) | 1999-04-15 | 2013-07-10 | Bristol-Myers Squibb Company | Cyclic protein tyrosine kinase inhibitors |
| US7291641B2 (en) | 1999-10-11 | 2007-11-06 | Societe De Conseils De Recherches Et D'applications Scientifiques (S.C.R.A.S.) | Derivatives of heterocycles with 5 members, their preparation and their use as medicaments |
| US20040132788A1 (en) | 1999-10-11 | 2004-07-08 | Chabrier De Lassauniere Pierre-Etienne | Derivatives of heterocycles with 5 members, their preparation and their use as medicaments |
| EP1125579A3 (en) | 2000-01-18 | 2003-01-02 | Pfizer Products Inc. | Uses of agrp-melanocortin receptor binding modulating compounds |
| DE10006453A1 (de) | 2000-02-14 | 2001-08-16 | Bayer Ag | Piperidylcarbonsäuren als Integrinantagonisten |
| JP2004502681A (ja) | 2000-06-29 | 2004-01-29 | アボット・ラボラトリーズ | アリールフェニル複素環スルフィド誘導体および細胞接着を阻止する抗炎症性および免疫抑制性物質としてのその使用 |
| HUP0202719A3 (en) | 2001-08-21 | 2006-01-30 | Pfizer Prod Inc | Pharmaceutical compositions for the treatment of female sexual dysfunctions |
| EP1435951B1 (en) | 2001-10-12 | 2006-01-18 | Bayer Pharmaceuticals Corporation | Phenyl substituted 5-membered nitrogen containing heterocycles for the tretment of obesity |
| DK1446394T3 (da) | 2001-11-08 | 2007-03-12 | Ortho Mcneil Pharm Inc | Hidtil ukendte 1,2,4-thiadiazolderivater som melanocortinreceptormodulatorer |
| CA2469228A1 (en) | 2001-12-03 | 2003-06-12 | Japan Tobacco Inc. | Azole compound and medicinal use thereof |
| US20030158199A1 (en) | 2002-01-25 | 2003-08-21 | Kylix, B.V. | Novel compounds for inhibition of Tie-2 |
| AU2003216274A1 (en) | 2002-02-11 | 2003-09-04 | Neurocrine Biosciences, Inc. | Pyrrole derivatives as ligands of melanocortin receptors |
| CA2488725A1 (en) | 2002-07-03 | 2004-01-15 | Su Qian | Agouti-related protein deficient cells, non-human transgenic animals and methods of selecting compounds which regulate energy metabolism |
| JP2006502131A (ja) | 2002-08-07 | 2006-01-19 | エフ．ホフマン−ラ ロシュ アーゲー | チアゾール誘導体 |
| KR20050119201A (ko) | 2003-04-09 | 2005-12-20 | 니뽄 다바코 산교 가부시키가이샤 | ５원 헤테로방향족 고리 화합물 및 이의 의약적 용도 |
| US20050009891A1 (en) | 2003-07-09 | 2005-01-13 | Lee Francis Y. | Combination of SRC Kinase inhibitors and chemotherapeutic agents for the treatment of proliferative diseases |
| JP4879165B2 (ja) * | 2004-04-20 | 2012-02-22 | トランス テック ファーマ，インコーポレイテッド | メラノコルチン受容体の調節因子としての置換チアゾール及びピリミジン誘導体 |
| WO2006038594A1 (ja) | 2004-10-04 | 2006-04-13 | Ono Pharmaceutical Co., Ltd. | Ｎ型カルシウムチャネル阻害薬 |
| US7361672B2 (en) | 2004-12-23 | 2008-04-22 | Hoffmann-La Roche Inc. | Heteroarylacetamide inhibitors of factor Xa |
| JP2009529059A (ja) | 2006-03-08 | 2009-08-13 | アキリオン ファーマシューティカルズ，インコーポレーテッド | 抗ｃ型肝炎ウイルス活性を有する置換アミノチアゾール誘導体 |
-
2009
- 2009-08-25 CA CA2731442A patent/CA2731442A1/en not_active Abandoned
- 2009-08-25 JP JP2011525147A patent/JP2012501334A/ja active Pending
- 2009-08-25 US US12/547,018 patent/US8563742B2/en not_active Expired - Fee Related
- 2009-08-25 WO PCT/US2009/054920 patent/WO2010025142A1/en not_active Ceased
- 2009-08-25 EP EP09810508A patent/EP2320738A4/en not_active Withdrawn
Also Published As
| Publication number | Publication date |
|---|---|
| US20100056587A1 (en) | 2010-03-04 |
| US8563742B2 (en) | 2013-10-22 |
| CA2731442A1 (en) | 2010-03-04 |
| WO2010025142A1 (en) | 2010-03-04 |
| EP2320738A1 (en) | 2011-05-18 |
| EP2320738A4 (en) | 2011-08-24 |
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