TWI328586B - Novel 1,2,4-thiadiazole derivatives as melanocortin receptor modulators - Google Patents
Novel 1,2,4-thiadiazole derivatives as melanocortin receptor modulators Download PDFInfo
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- TWI328586B TWI328586B TW091133320A TW91133320A TWI328586B TW I328586 B TWI328586 B TW I328586B TW 091133320 A TW091133320 A TW 091133320A TW 91133320 A TW91133320 A TW 91133320A TW I328586 B TWI328586 B TW I328586B
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Classifications
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- C07D285/02—Thiadiazoles; Hydrogenated thiadiazoles
- C07D285/04—Thiadiazoles; Hydrogenated thiadiazoles not condensed with other rings
- C07D285/08—1,2,4-Thiadiazoles; Hydrogenated 1,2,4-thiadiazoles
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- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
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- 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)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
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- Oncology (AREA)
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- Child & Adolescent Psychology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US33792701P | 2001-11-08 | 2001-11-08 |
Publications (2)
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| TW200303311A TW200303311A (en) | 2003-09-01 |
| TWI328586B true TWI328586B (en) | 2010-08-11 |
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| TW091133320A TWI328586B (en) | 2001-11-08 | 2002-11-08 | Novel 1,2,4-thiadiazole derivatives as melanocortin receptor modulators |
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|---|---|
| US (2) | US7049331B2 (https=) |
| EP (1) | EP1446394B1 (https=) |
| JP (1) | JP4436676B2 (https=) |
| CN (1) | CN1312139C (https=) |
| AR (1) | AR037331A1 (https=) |
| AT (1) | ATE344254T1 (https=) |
| AU (1) | AU2009201842B2 (https=) |
| BR (1) | BR0214024A (https=) |
| CA (1) | CA2466140C (https=) |
| CY (1) | CY1105907T1 (https=) |
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| ES (1) | ES2275918T3 (https=) |
| IL (1) | IL161829A (https=) |
| MX (1) | MXPA04004458A (https=) |
| MY (1) | MY134993A (https=) |
| NO (1) | NO328195B1 (https=) |
| NZ (1) | NZ532883A (https=) |
| PT (1) | PT1446394E (https=) |
| RS (1) | RS51530B (https=) |
| RU (1) | RU2317292C2 (https=) |
| SG (1) | SG176310A1 (https=) |
| SI (1) | SI1446394T1 (https=) |
| TW (1) | TWI328586B (https=) |
| WO (1) | WO2003040117A1 (https=) |
| ZA (1) | ZA200404484B (https=) |
Families Citing this family (43)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7732451B2 (en) | 2001-08-10 | 2010-06-08 | Palatin Technologies, Inc. | Naphthalene-containing melanocortin receptor-specific small molecule |
| US7655658B2 (en) | 2001-08-10 | 2010-02-02 | Palatin Technologies, Inc. | Thieno [2,3-D]pyrimidine-2,4-dione melanocortin-specific compounds |
| US7456184B2 (en) | 2003-05-01 | 2008-11-25 | Palatin Technologies Inc. | Melanocortin receptor-specific compounds |
| AU2002331064B2 (en) | 2001-08-10 | 2007-08-23 | Palatin Technologies, Inc. | Peptidomimetics of biologically active metallopeptides |
| US7718802B2 (en) | 2001-08-10 | 2010-05-18 | Palatin Technologies, Inc. | Substituted melanocortin receptor-specific piperazine compounds |
| RU2317292C2 (ru) * | 2001-11-08 | 2008-02-20 | Орто-Макнейл Фармасьютикал, Инк. | Новые производные 1,2,4-тиадиазола в качестве модуляторов рецепторов меланокортина |
| US7319107B2 (en) * | 2001-11-08 | 2008-01-15 | Johnson & Johnson Consumer Companies, Inc. | 1,2,4-thiadiazolium derivatives as melanocortin receptor modulators |
| US7727990B2 (en) | 2003-05-01 | 2010-06-01 | Palatin Technologies, Inc. | Melanocortin receptor-specific piperazine and keto-piperazine compounds |
| US7968548B2 (en) * | 2003-05-01 | 2011-06-28 | Palatin Technologies, Inc. | Melanocortin receptor-specific piperazine compounds with diamine groups |
| US7727991B2 (en) | 2003-05-01 | 2010-06-01 | Palatin Technologies, Inc. | Substituted melanocortin receptor-specific single acyl piperazine compounds |
| WO2005054849A2 (en) * | 2003-12-06 | 2005-06-16 | Bayer Healthcare Ag | Diagnostics and therapeutics for diseases associated with g protein-coupled receptor mc5 (mc5r) |
| EP1734963A4 (en) | 2004-04-02 | 2008-06-18 | Merck & Co Inc | METHOD FOR TREATING PEOPLE WITH METABOLIC AND ANTHROPOMETRIC DISORDER |
| US7709484B1 (en) | 2004-04-19 | 2010-05-04 | Palatin Technologies, Inc. | Substituted melanocortin receptor-specific piperazine compounds |
| AU2005236055B2 (en) | 2004-04-20 | 2011-10-06 | Transtech Pharma, Llc | Substituted thiazole and pyrimidine derivatives as melanocortin receptor modulators |
| US8394765B2 (en) | 2004-11-01 | 2013-03-12 | Amylin Pharmaceuticals Llc | Methods of treating obesity with two different anti-obesity agents |
| CN101094689B (zh) | 2004-11-01 | 2013-06-12 | 安米林药品有限责任公司 | 治疗肥胖以及肥胖相关疾病和病症的方法 |
| WO2007022123A2 (en) | 2005-08-11 | 2007-02-22 | Amylin Pharmaceuticals, Inc. | Hybrid polypeptides with selectable properties |
| US20070021433A1 (en) | 2005-06-03 | 2007-01-25 | Jian-Qiang Fan | Pharmacological chaperones for treating obesity |
| EP2330125A3 (en) | 2005-08-11 | 2012-12-12 | Amylin Pharmaceuticals, Inc. | Hybrid polypeptides with selectable properties |
| US7834017B2 (en) | 2006-08-11 | 2010-11-16 | Palatin Technologies, Inc. | Diamine-containing, tetra-substituted piperazine compounds having identical 1- and 4-substituents |
| US7704533B2 (en) * | 2006-12-13 | 2010-04-27 | J&J Consumer Companies, Inc. | Compositions and methods of inducing hair growth utilizing Continus coggygria |
| JP5383498B2 (ja) * | 2006-12-14 | 2014-01-08 | ニューロノバ エービー | メラノコルチン４レセプターの活性を低下させる薬剤を使用した、神経系の疾患または損傷の処置 |
| RU2348623C1 (ru) * | 2007-05-21 | 2009-03-10 | Государственное образовательное учреждение высшего профессионального образования "Ивановский государственный химико-технологический университет" (ИГХТУ) | Способ получения 3,5-диамино-1,2,4-тиадиазола |
| EP2278962B1 (en) * | 2008-02-21 | 2014-02-12 | Janssen Pharmaceutica N.V. | Methods for the treatment of dermatological disorders |
| US8008291B2 (en) * | 2008-02-29 | 2011-08-30 | Mimetica Pty Ltd | 3-aminoalkyl-1,4-diazepan-2-one melanocortin-5 receptor antagonists |
| US8377925B2 (en) | 2008-02-29 | 2013-02-19 | Mimetica Pty Ltd | Methods of modulating the activity of the MC5 receptor and treatment of conditions related to this receptor |
| US8343958B2 (en) | 2008-02-29 | 2013-01-01 | Mimetica Pty Ltd | 3-aminoalkyl-1,4-diazepan-2-one melanocortin-5-receptor antagonists |
| US8563742B2 (en) | 2008-08-29 | 2013-10-22 | High Point Pharmaceuticals, Llc | Substituted aminothiazole derivatives, pharmaceutical compositions, and methods of use |
| EP2358200A4 (en) | 2008-11-17 | 2012-05-16 | Merck Sharp & Dohme | SUBSTITUTED BICYCLIC AMINES FOR THE TREATMENT OF DIABETES |
| NZ596138A (en) * | 2009-04-24 | 2013-11-29 | Janssen Pharmaceuticals Inc | Stable topical compositions for 1,2,4-thiadiazole derivatives |
| WO2011011506A1 (en) | 2009-07-23 | 2011-01-27 | Schering Corporation | Spirocyclic oxazepine compounds as stearoyl-coenzyme a delta-9 desaturase inhibitors |
| CA2768577A1 (en) | 2009-07-23 | 2011-01-27 | Schering Corporation | Benzo-fused oxazepine compounds as stearoyl-coenzyme a delta-9 desaturase inhibitors |
| ES2360783B1 (es) * | 2009-10-02 | 2012-07-04 | Consejo Superior De Investigaciones Científicas (Csic) | 1,2,4-tiadiazoles-5-imino sustituidos utiles en el tratamiento de enfermedades neurodegenerativas |
| US8470833B2 (en) | 2009-12-15 | 2013-06-25 | Mcneil-Ppc, Inc. | Hair growth and/or regrowth compositions |
| US8470880B2 (en) | 2009-12-15 | 2013-06-25 | Mcneil-Ppc, Inc. | Methods of reducing hair loss and/or facilitating hair growth and/or regrowth |
| WO2011137024A1 (en) | 2010-04-26 | 2011-11-03 | Merck Sharp & Dohme Corp. | Novel spiropiperidine prolylcarboxypeptidase inhibitors |
| EP2568812B1 (en) | 2010-05-11 | 2016-10-26 | Merck Sharp & Dohme Corp. | Novel prolylcarboxypeptidase inhibitors |
| WO2011156246A1 (en) | 2010-06-11 | 2011-12-15 | Merck Sharp & Dohme Corp. | Novel prolylcarboxypeptidase inhibitors |
| WO2012100342A1 (en) | 2011-01-27 | 2012-08-02 | Université de Montréal | Pyrazolopyridine and pyrazolopyrimidine derivatives as melanocortin-4 receptor modulators |
| ES2877570T3 (es) | 2012-08-22 | 2021-11-17 | Univ Cornell | Métodos para inhibir fascina |
| US8962041B2 (en) | 2013-02-12 | 2015-02-24 | Johnson & Johnson Consumer Companies, Inc. | Methods and compositions for enhancing hair quality using blackberry extract |
| US9573946B2 (en) | 2014-02-20 | 2017-02-21 | Novita Pharmaceuticals, Inc. | Compounds and methods for inhibiting fascin |
| US20220135968A1 (en) * | 2018-06-15 | 2022-05-05 | Torrey Pines Law Group, PC | Treatment of synucleinopathy and animal models of synucleinopathy |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE131373C (https=) | ||||
| JPS6011481A (ja) | 1983-06-30 | 1985-01-21 | Nippon Soda Co Ltd | １，２，４−チアジアゾ−ル系誘導体及び農園芸用殺菌剤 |
| JPH02173165A (ja) | 1988-12-27 | 1990-07-04 | Nippon Soda Co Ltd | 防汚剤 |
| TR199903082T2 (xx) * | 1997-06-24 | 2000-07-21 | Janssen Pharmaceutica N.V. | Anjiogenez inhibit�r� 5-s�bstit�e-1,2,4,-tiadiazolil t�revleri. |
| EP1076649A4 (en) | 1998-04-28 | 2010-06-02 | Trega Biosciences Inc | ISOQUINOLINE-BASED COMPOUNDS IN PLACE OF MELANOCORTIN RECEPTOR LIGANDS AND METHODS OF USE |
| EP1076648B1 (de) | 1998-04-29 | 2006-07-12 | MERCK PATENT GmbH | Verfahren zur katalytischen herstellung von substituierten bipyridylderivaten |
| US6294534B1 (en) * | 1998-06-11 | 2001-09-25 | Merck & Co., Inc. | Spiropiperidine derivatives as melanocortin receptor agonists |
| WO1999064002A1 (en) | 1998-06-11 | 1999-12-16 | Merck & Co., Inc. | Spiropiperidine derivatives as melanocortin receptor agonists |
| WO2000024725A1 (en) | 1998-10-26 | 2000-05-04 | Vertex Pharmaceuticals Incorporated | Pentacyclic compounds useful as inhibitors of hepatitis c virus ns3 helicase |
| WO2001055107A2 (en) * | 2000-01-28 | 2001-08-02 | Melacure Therapeutics Ab | Aromatic amines and amides acting on the melanocortin receptors |
| US7319107B2 (en) * | 2001-11-08 | 2008-01-15 | Johnson & Johnson Consumer Companies, Inc. | 1,2,4-thiadiazolium derivatives as melanocortin receptor modulators |
| RU2317292C2 (ru) * | 2001-11-08 | 2008-02-20 | Орто-Макнейл Фармасьютикал, Инк. | Новые производные 1,2,4-тиадиазола в качестве модуляторов рецепторов меланокортина |
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