ZA200603419B - Tetrazole derivatives and methods of treatment of metabolic-related disorders thereof - Google Patents
Tetrazole derivatives and methods of treatment of metabolic-related disorders thereof Download PDFInfo
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- ZA200603419B ZA200603419B ZA200603419A ZA200603419A ZA200603419B ZA 200603419 B ZA200603419 B ZA 200603419B ZA 200603419 A ZA200603419 A ZA 200603419A ZA 200603419 A ZA200603419 A ZA 200603419A ZA 200603419 B ZA200603419 B ZA 200603419B
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- South Africa
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- compound according
- solvate
- hydrate
- acceptable salt
- pharmaceutically acceptable
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- 238000011282 treatment Methods 0.000 title claims description 22
- 238000000034 method Methods 0.000 title claims description 19
- 230000002503 metabolic effect Effects 0.000 title claims description 14
- 150000003536 tetrazoles Chemical class 0.000 title description 7
- 150000001875 compounds Chemical class 0.000 claims description 88
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 47
- 150000003839 salts Chemical class 0.000 claims description 34
- 239000012453 solvate Substances 0.000 claims description 33
- 125000000217 alkyl group Chemical group 0.000 claims description 32
- 229910052736 halogen Inorganic materials 0.000 claims description 27
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 27
- 125000001188 haloalkyl group Chemical group 0.000 claims description 22
- 125000003545 alkoxy group Chemical group 0.000 claims description 20
- 150000002367 halogens Chemical class 0.000 claims description 20
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- 125000003342 alkenyl group Chemical group 0.000 claims description 14
- 125000000304 alkynyl group Chemical group 0.000 claims description 14
- 125000001424 substituent group Chemical group 0.000 claims description 14
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- LTQYSJKGRPGMPO-UHFFFAOYSA-N 3-(2h-tetrazol-5-yl)-1,4,5,6-tetrahydrocyclopenta[c]pyrazole Chemical compound C1=2CCCC=2NN=C1C1=NN=NN1 LTQYSJKGRPGMPO-UHFFFAOYSA-N 0.000 claims 1
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- SWSJDJYGSQGAFF-UHFFFAOYSA-N 3-(2h-tetrazol-5-yl)-1,6-dihydrocyclopenta[c]pyrazole Chemical compound C1C=CC2=C1NN=C2C1=NN=NN1 SWSJDJYGSQGAFF-UHFFFAOYSA-N 0.000 claims 1
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- CXBPIKBDSFXEMF-UHFFFAOYSA-N 3-(2h-tetrazol-5-yl)-4,6-dihydro-1h-thieno[3,4-c]pyrazole Chemical compound C1SCC=2C1=NNC=2C1=NN=NN1 CXBPIKBDSFXEMF-UHFFFAOYSA-N 0.000 claims 1
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Classifications
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
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- 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
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- A61P5/50—Drugs for disorders of the endocrine system of the pancreatic hormones for increasing or potentiating the activity of insulin
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- 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
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- A—HUMAN NECESSITIES
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- A61P9/12—Antihypertensives
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
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- Emergency Medicine (AREA)
- Child & Adolescent Psychology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
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| US51623803P | 2003-10-31 | 2003-10-31 |
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| ZA200603419B true ZA200603419B (en) | 2006-10-25 |
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| ZA200603419A ZA200603419B (en) | 2003-10-31 | 2006-04-28 | Tetrazole derivatives and methods of treatment of metabolic-related disorders thereof |
| ZA200606203A ZA200606203B (en) | 2003-10-31 | 2006-07-26 | Tetrazole derivatives and methods of treatment of metabolic-related disorders thereof |
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| ZA200606203A ZA200606203B (en) | 2003-10-31 | 2006-07-26 | Tetrazole derivatives and methods of treatment of metabolic-related disorders thereof |
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| CN (1) | CN1867562B (de) |
| AR (1) | AR046611A1 (de) |
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| BR (1) | BRPI0415631A (de) |
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| CR (1) | CR8270A (de) |
| CY (1) | CY1105479T1 (de) |
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| EC (1) | ECSP066529A (de) |
| ES (1) | ES2267077T3 (de) |
| GE (1) | GEP20094801B (de) |
| HK (1) | HK1076468A1 (de) |
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| RS (1) | RS20060290A (de) |
| SI (1) | SI1599469T1 (de) |
| TN (1) | TNSN06150A1 (de) |
| TW (1) | TWI258478B (de) |
| UA (1) | UA86783C2 (de) |
| WO (1) | WO2005044816A1 (de) |
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| TWI258478B (en) | 2003-10-31 | 2006-07-21 | Arena Pharm Inc | Tetrazole derivatives and methods of treatment of metabolic-related disorders thereof |
| US20070093545A1 (en) * | 2003-11-21 | 2007-04-26 | Arena Pharmaceuticals, Inc. | 4-Oxo-4,5-dihydro-furan-2-carboxylic acid derivatives and methods of treatment of metabolic-related disorders thereof |
| US20070244107A1 (en) * | 2004-08-25 | 2007-10-18 | Waters M Gerard | Method of Treating Atherosclerosis, Dyslipidemias and Related Conditions |
| CA2584225A1 (en) * | 2004-11-05 | 2006-05-18 | Arena Pharmaceuticals, Inc. | Compositions for treating flushing and lipid-associated disorders comprising niacin receptor partial agonists |
| PE20060949A1 (es) * | 2004-12-23 | 2006-10-11 | Arena Pharm Inc | Derivados fusionados de pirazol como agonistas del receptor de niacina |
| EP1877402A1 (de) | 2005-04-28 | 2008-01-16 | Merck Sharp & Dohme Limited | Verfahren zur herstellung von tetrazolyltetrahydrocyclopentapyrazolen |
| US8168649B2 (en) | 2005-06-28 | 2012-05-01 | Merk Sharp & Dohme Corp. | Niacin receptor agonists, compositions containing such compounds and methods of treatment |
| DE102006021733A1 (de) * | 2006-05-09 | 2007-11-22 | Bayer Healthcare Ag | 3-Tetrazolylindazole und 3-Tetrazolylpyrazolopyridine sowie ihre Verwendung |
| DE102006043443A1 (de) | 2006-09-15 | 2008-03-27 | Bayer Healthcare Ag | Neue aza-bicyclische Verbindungen und ihre Verwendung |
| DE102008063992A1 (de) | 2008-12-19 | 2010-09-02 | Lerner, Zinoviy, Dipl.-Ing. | Neue aliphatisch substituierte Pyrazolopyridine und ihre Verwendung |
| DE102010021637A1 (de) | 2010-05-26 | 2011-12-01 | Bayer Schering Pharma Aktiengesellschaft | Substituierte 5-Fluor-1H-Pyrazolopyridine und ihre Verwendung |
| WO2014011926A1 (en) | 2012-07-11 | 2014-01-16 | Elcelyx Therapeutics, Inc. | Compositions comprising statins, biguanides and further agents for reducing cardiometabolic risk |
| EP2958914B1 (de) | 2013-02-21 | 2020-07-15 | Adverio Pharma GmbH | Formen von {4,6-diamino-2-[1-(2-fluorbenzyl)-1h-pyrazolo[3,4-b]pyridino-3-yl]pyrimidino-5-yl}methylcarbamat |
| JP6453216B2 (ja) * | 2013-07-23 | 2019-01-16 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | ヘテロ縮合環化合物 |
| CN103755637A (zh) * | 2013-12-26 | 2014-04-30 | 平湖优康药物研发有限公司 | 一种医药中间体1,4,5,6-四氢-3-环戊并吡唑甲腈的合成工艺 |
| US20210110275A1 (en) * | 2019-10-11 | 2021-04-15 | Royal Bank Of Canada | System and method of machine learning using embedding networks |
Family Cites Families (36)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH02178263A (ja) * | 1988-12-27 | 1990-07-11 | Kaken Pharmaceut Co Ltd | アザアズレン誘導体、その製造法およびそれを有効成分とする抗アレルギー剤および抗炎症剤 |
| US5134155A (en) * | 1991-08-08 | 1992-07-28 | Ortho Pharmaceutical Corporation | Tetrahydroindazole, tetrahydrocyclopentapyrazole, and hexahydrocycloheptapyrazole compounds and their use as HMG-coA reductase inhibitors |
| US5948786A (en) | 1996-04-12 | 1999-09-07 | Sumitomo Pharmaceuticals Company, Limited | Piperidinylpyrimidine derivatives |
| EA003056B1 (ru) | 1996-12-23 | 2002-12-26 | Дюпон Фармасьютикалз Компани | АЗОТСОДЕРЖАЩИЕ ГЕТЕРОАРОМАТИЧЕСКИЕ СОЕДИНЕНИЯ В КАЧЕСТВЕ ИНГИБИТОРОВ ФАКТОРА Ха, ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ И СПОСОБ ЛЕЧЕНИЯ |
| JP4345230B2 (ja) | 1998-03-10 | 2009-10-14 | 小野薬品工業株式会社 | カルボン酸誘導体およびその誘導体を有効成分として含有する薬剤 |
| US6414002B1 (en) | 1999-09-22 | 2002-07-02 | Bristol-Myers Squibb Company | Substituted acid derivatives useful as antidiabetic and antiobesity agents and method |
| WO2003022814A1 (fr) | 2001-09-07 | 2003-03-20 | Ono Pharmaceutical Co., Ltd. | Derives d'indole |
| WO2001066520A1 (fr) | 2000-03-09 | 2001-09-13 | Ono Pharmaceutical Co., Ltd. | Derives indole, procede de preparation de ces derives et leur utilisation |
| US20010047027A1 (en) | 2000-04-12 | 2001-11-29 | Marc Labelle | Prostaglandin D2 receptor antagonists |
| KR20080064908A (ko) | 2000-06-28 | 2008-07-09 | 테바 파마슈티컬 인더스트리즈 리미티드 | 카르베딜올 |
| TW200914443A (en) | 2000-06-30 | 2009-04-01 | Glaxo Group Ltd | Process for preparing substituted quinazolinyl furanaldehyde |
| US6410583B1 (en) | 2000-07-25 | 2002-06-25 | Merck Frosst Canada & Co. | Cyclopentanoindoles, compositions containing such compounds and methods of treatment |
| DE10057751A1 (de) | 2000-11-22 | 2002-05-23 | Bayer Ag | Neue Carbamat-substituierte Pyrazolopyridinderivate |
| JP4279561B2 (ja) | 2001-05-23 | 2009-06-17 | メルク フロスト カナダ リミテツド | プロスタグランジンＤ２受容体拮抗薬としてのジヒドロピロロ［１，２−ａ］インドールおよびテトラヒドロピリド［１，２−ａ］−インドール誘導体 |
| WO2002098864A1 (en) | 2001-06-01 | 2002-12-12 | F. Hoffmann-La Roche Ag | Pyrimidine, triazine and pyrazine derivatives as glutamate receptors |
| WO2003002544A1 (en) | 2001-06-26 | 2003-01-09 | Bristol-Myers Squibb Company | N-heterocyclic inhibitors of tnf-alpha expression |
| CN1233648C (zh) | 2001-06-27 | 2005-12-28 | 尔艾斯特公司 | Salen催化剂、催化剂的制备和通过使用催化剂制备手性化合物的方法 |
| DE10148617A1 (de) | 2001-09-25 | 2003-04-24 | Schering Ag | Substituierte N-(1,4,5,6-Tetrahydro-cyclopentapyrazol-3-yl)-Derivate, deren Herstellung und Verwendung als Arzneimittel |
| AR038136A1 (es) | 2002-01-24 | 2004-12-29 | Merck Frosst Canada Inc | Cicloalcanindoles con sustitucion con fluor composiciones que contienen estos compuestos y metodos de tratamiento |
| PL372466A1 (en) | 2002-03-19 | 2005-07-25 | Ono Pharmaceutical Co, Ltd. | Carboxylic acid compounds and drugs containing the compounds as the active ingredient |
| DE10220570A1 (de) | 2002-05-08 | 2003-11-20 | Bayer Ag | Carbamat-substituierte Pyrazolopyridine |
| WO2004033431A2 (en) | 2002-10-04 | 2004-04-22 | Arena Pharmaceuticals, Inc. | Hydroxypyrazoles for use against metabolic-related disorders |
| AU2003300014A1 (en) * | 2002-10-10 | 2004-05-04 | Arena Pharmaceuticals, Inc. | 5-substituted 2h-pyrazone-3-carboxylic acid derivatives as antilipolytic agents for the treatment of metabolic-related disorders such as dyslipidemia |
| DE10261131A1 (de) | 2002-12-20 | 2004-07-01 | Grünenthal GmbH | Substituierte 5-Aminomethyl-1H-pyrrol-2-carbonsäureamide |
| US7145012B2 (en) | 2003-04-23 | 2006-12-05 | Pfizer Inc. | Cannabinoid receptor ligands and uses thereof |
| AR041089A1 (es) | 2003-05-15 | 2005-05-04 | Merck & Co Inc | Procedimiento y composiciones farmaceutiicas para tratar aterosclerosis, dislipidemias y afecciones relacionadas |
| US7232823B2 (en) | 2003-06-09 | 2007-06-19 | Pfizer, Inc. | Cannabinoid receptor ligands and uses thereof |
| EP1633351A1 (de) | 2003-06-13 | 2006-03-15 | Arena Pharmaceuticals, Inc. | 5-substituierte 2h-pyrazol-3-carbonsäure-derivate als agonisten für den nicotinsäure-rezeptor rup25 zur behandlung von dyslipidämie und verwandten erkrankungen |
| GB0319126D0 (en) | 2003-08-14 | 2003-09-17 | Smithkline Beecham Corp | Chemical compounds |
| GB0319124D0 (en) | 2003-08-14 | 2003-09-17 | Smithkline Beecham Corp | Chemical compounds |
| TWI258478B (en) | 2003-10-31 | 2006-07-21 | Arena Pharm Inc | Tetrazole derivatives and methods of treatment of metabolic-related disorders thereof |
| CA2556073C (en) | 2004-02-14 | 2012-01-10 | Smithkline Beecham Corporation | 8-chloro-1,3-disubstituted xanthine derivatives as hm74a receptor modulators |
| US20070244107A1 (en) | 2004-08-25 | 2007-10-18 | Waters M Gerard | Method of Treating Atherosclerosis, Dyslipidemias and Related Conditions |
| CA2584225A1 (en) | 2004-11-05 | 2006-05-18 | Arena Pharmaceuticals, Inc. | Compositions for treating flushing and lipid-associated disorders comprising niacin receptor partial agonists |
| PE20060949A1 (es) | 2004-12-23 | 2006-10-11 | Arena Pharm Inc | Derivados fusionados de pirazol como agonistas del receptor de niacina |
| EP1877402A1 (de) | 2005-04-28 | 2008-01-16 | Merck Sharp & Dohme Limited | Verfahren zur herstellung von tetrazolyltetrahydrocyclopentapyrazolen |
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