{5-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethoxy]-indol-1-yl}-acetic acid

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: {5-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethoxy]-indol-1-yl}-acetic acid
• 英文别名: 2-[5-[[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]methoxy]indol-1-yl]acetic Acid
• 化学式: C₂₂H₁₇F₃N₂O₃S
• 分子量: 446.45
• InChiKey: PVPSIHNTBHEDBR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  92.6
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  5-苄氧基吲哚 在 palladium on activated charcoal lithium hydroxide 、 氢气 、 sodium hydride 、 caesium carbonate 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 生成 {5-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethoxy]-indol-1-yl}-acetic acid
  参考文献：
  名称：

  选择性苯并噻吩，苯并呋喃和吲哚基过氧化物酶体增殖物激活的受体δ激动剂的合成和SAR。

  摘要：

  最近的文献表明，选择性PPARδ激动剂可用于治疗动脉粥样硬化和与代谢综合征相关的其他疾病。在本文中，我们报告了一系列新型和选择性的PPARδ激动剂的合成与构效关系。我们的搜索始于鉴定新的苯并噻吩模板，该模板已通过添加各种噻唑基，异恶唑基和苄氧基-苄基部分进行了修饰。SAR的进一步阐明导致鉴定了基于苯并呋喃和吲哚的模板。在我们的研究过程中，我们发现了三种新的化学模板，它们与PPARalpha和PPARgamma亚型相比，对PPARdelta具有不同程度的亲和力和效价。

  DOI：

  10.1016/j.bmcl.2007.04.047

文献信息

• [EN] (5- (2-PHENYL)-THIAZOL-5-YLMETHOXY)-INDOL-1-YL) -ACETIC ACID DERIVATIVES AND RELATED COMPOUNDS AS MODULATORS OF THE HUMAN PPAR-DELTA RECEPTOR FOR THE TREATMENT OF METABOLIC DISORDERS SUCH AS TYPE 2 DIABETES<br/>[FR] DERIVES DE L'ACIDE (5- (2-PHENYL)-THIAZOL-5-YLMETHOXY)-INDOL-1-YL) -ACETIQUE ET COMPOSES ASSOCIES EN TANT QUE MODULATEURS DU RECEPTEUR PPAR-DELTA HUMAIN POUR LE TRAITEMENT DE TROUBLES METABOLIQUES TELS QUE LE DIABETE DE TYPE 2
  申请人：KALYPSYS INC

  公开号：WO2005060958A1

  公开（公告）日：2005-07-07

  Disclosed are compounds having the structure of Formula (I) and pharmaceutically acceptable salts and solvates thereof [A]-[B]-[C] (I) wherein (a) [A] is [H]-[L]; wherein [H] represents a CCOH (or a hydrolyzable ester thereof) or tetrazole group [L] is: formula (II), b) [B] is a ring system selected from the group consisting of: e.g. formula (III); (IIIA), c) [C] is e.g. formula (IV); the other substituents and variables are defined in the claims; as modulators of the human PPAR-delta receptor for the treatment of metabolic disorders such as type 2 diabetes.

  揭示了具有以下结构的化合物及其药学上可接受的盐和溶剂化合物[A]-[B]-[C] (I) 其中 (a) [A] 是 [H]-[L]; 其中 [H] 代表 CCOH (或其可水解酯) 或四唑基团 [L] 是：式 (II), b) [B] 是从以下群组中选择的环系统：例如式 (III); (IIIA), c) [C] 是例如式 (IV); 其他取代基和变量在权利要求中定义; 作为人类PPAR-δ受体的调节剂，用于治疗代谢性疾病，如2型糖尿病。
• Thiazolyl-indole derivatives, their manufacture and use as pharmaceutical agents
  申请人：Ackermann Jean

  公开号：US20050004187A1

  公开（公告）日：2005-01-06

  This invention relates to compounds of the formula wherein one of R 6 , R 7 or R 8 is and all enantiomers and pharmaceutically acceptable salts and/or esters thereof as well as pharmaceutical compositions containing such compounds, to a process for their preparation and to their use for the treatment and/or prevention of diseases which are modulated by PPARδ and/or PPARα agonists.

  这项发明涉及以下式的化合物 其中R 6 、R 7 或R 8 中的一个是 以及所有的对映体和药学上可接受的盐和/或酯，以及含有这种化合物的药物组合物，以及它们的制备方法和它们用于治疗和/或预防由PPARδ和/或PPARα激动剂调节的疾病。
• Compounds that modulate PPAR activity and methods of preparation
  申请人：——

  公开号：US20030207915A1

  公开（公告）日：2003-11-06

  This invention discloses compounds that alter PPAR activity. The invention also discloses pharmaceutically acceptable salts of the compounds, pharmaceutically acceptable compositions comprising the compounds or their salts, and methods of using them as therapeutic agents for treating or preventing hyperlipidemia and hypercholesteremia in a mammal. The present invention also discloses method for making the disclosed compounds.

  这项发明揭示了能够改变PPAR活性的化合物。该发明还揭示了这些化合物的药用盐、包含这些化合物或其盐的药用组合物，以及将它们用作治疗或预防哺乳动物高脂血症和高胆固醇血症的治疗剂的方法。本发明还揭示了制备所述化合物的方法。
• Novel compounds, compositions and uses thereof for treatment of metabolic disorders and related conditions
  申请人：Malecha William James

  公开号：US20050203151A1

  公开（公告）日：2005-09-15

  Described herein are novel mono- and bicyclic compounds compounds, including compounds capable of modulating the activity of human peroxisome proliferator activated receptor of the subtype delta (hPPAR-delta), and methods for utilizing such modulation to treat a disease or condition mediated or impacted by hPPAR-delta activity such as Type 2 diabetes, syndrome X, dyslipidemia, and atherosclerotic diseases including vascular disease, coronary heart disease, cerebrovascular disease, and peripheral vessel disease. Also described are compounds that mediate and/or inhibit the activity of hPPAR-delta, and pharmaceutical compositions containing such compounds or pharmaceutically acceptable prodrugs, solvates, salts, esters, thioesters, or amides or pharmaceutically active metabolites thereof. Further described are methods for making and producing such compounds. Also described are the therapeutic or prophylactic use of such compounds or compositions, and methods of treating metabolic disorders and conditions, by administering effective amounts of such compounds.

  本文介绍了新型的单环和双环化合物，包括能够调节人类过氧化物酶体增殖物激活受体δ亚型（hPPAR-δ）活性的化合物，以及利用这种调节方法治疗由hPPAR-δ活性介导或影响的疾病或病况的方法，例如2型糖尿病、X综合症、血脂异常和动脉粥样硬化性疾病，包括血管疾病、冠心病、脑血管疾病和周围血管疾病。还介绍了介导和/或抑制hPPAR-δ活性的化合物，以及含有这种化合物或其药学上可接受的前药、溶剂、盐、酯、硫酯或酰胺或其药学活性代谢物的制药组合物。还介绍了制备这种化合物的方法。还介绍了这种化合物或组合物的治疗或预防用途，以及通过给予这种化合物的有效量来治疗代谢性疾病和病况的方法。
• INDOLYL DERIVATIVES SUBSTITUTED WITH A THIAZOLE RING AND THEIR USE AS PPAR MODULATORS
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP1644368A1

  公开（公告）日：2006-04-12