2-{4-[3-(3-Fluoro-4-trifluoromethyl-phenyl)-[1,2,4]thiadiazol-5-ylmethylsulfanyl]-2-methyl-phenoxy}-2-methyl-propionic acid ethyl ester | 851225-29-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-{4-[3-(3-Fluoro-4-trifluoromethyl-phenyl)-[1,2,4]thiadiazol-5-ylmethylsulfanyl]-2-methyl-phenoxy}-2-methyl-propionic acid ethyl ester
• 英文别名: Ethyl 2-[4-[[3-[3-fluoro-4-(trifluoromethyl)phenyl]-1,2,4-thiadiazol-5-yl]methylsulfanyl]-2-methylphenoxy]-2-methylpropanoate
• CAS: 851225-29-1
• 化学式: C₂₃H₂₂F₄N₂O₃S₂
• 分子量: 514.565
• InChiKey: KDICKIDOEXWLFU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.7
• 重原子数：
  34
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  115
• 氢给体数：
  0
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  2-{4-[3-(3-Fluoro-4-trifluoromethyl-phenyl)-[1,2,4]thiadiazol-5-ylmethylsulfanyl]-2-methyl-phenoxy}-2-methyl-propionic acid ethyl ester 在 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 4.0h， 以99%的产率得到2-{4-[3-(3-Fluoro-4-trifluoromethyl-phenyl)-[1,2,4]thiadiazol-5-ylmethylsulfanyl]-2-methyl-phenoxy}-2-methyl-propionic acid
  参考文献：
  名称：

  Synthesis and structure–activity relationships of thiadiazole-derivatives as potent and orally active peroxisome proliferator-activated receptors α/δ dual agonists

  摘要：

  Replacement of the methyl-thiazole moiety of GW501516 (a PPAR delta selective agonist) with [1,2,4]thiadiazole gave compound 21 which unexpectedly displayed submicromolar potency as a partial agonist at PPAR alpha in addition to the high potency at PPAR delta. A structure-activity relationships study of 21 resulted in the identification of 40 as a potent and selective PPAR alpha/delta dual agonist. Compound 40 and its close analogs represent a new series of PPAR alpha/delta dual agonists. The high potency, high selectivity, significant gene induction, excellent PK profiles, low P450 inhibition or induction, and good in vivo efficacy in four animal models support 40 being selected as a pre-clinical study candidate, and may render 40 as a valuable pharmacological tool in elucidating the complex roles of PPAR alpha/delta dual agonists, and the potential usage for the treatment of metabolic syndrome. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.12.005
• 作为产物：
  描述：

  2-(4-疏基-2-甲基苯氧基)-2-甲基丙酸乙酯 、 5-Bromomethyl-3-(3-fluoro-4-trifluoromethyl-phenyl)-[1,2,4]thiadiazole 在 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 0.25h， 以79%的产率得到2-{4-[3-(3-Fluoro-4-trifluoromethyl-phenyl)-[1,2,4]thiadiazol-5-ylmethylsulfanyl]-2-methyl-phenoxy}-2-methyl-propionic acid ethyl ester
  参考文献：
  名称：

  Synthesis and structure–activity relationships of thiadiazole-derivatives as potent and orally active peroxisome proliferator-activated receptors α/δ dual agonists

  摘要：

  Replacement of the methyl-thiazole moiety of GW501516 (a PPAR delta selective agonist) with [1,2,4]thiadiazole gave compound 21 which unexpectedly displayed submicromolar potency as a partial agonist at PPAR alpha in addition to the high potency at PPAR delta. A structure-activity relationships study of 21 resulted in the identification of 40 as a potent and selective PPAR alpha/delta dual agonist. Compound 40 and its close analogs represent a new series of PPAR alpha/delta dual agonists. The high potency, high selectivity, significant gene induction, excellent PK profiles, low P450 inhibition or induction, and good in vivo efficacy in four animal models support 40 being selected as a pre-clinical study candidate, and may render 40 as a valuable pharmacological tool in elucidating the complex roles of PPAR alpha/delta dual agonists, and the potential usage for the treatment of metabolic syndrome. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.12.005

文献信息

• 4-((Phenoxyalkyl)thio)-phenoxyacetic acids and analogs
  申请人：Kuo Gee-Hong

  公开号：US20050096362A1

  公开（公告）日：2005-05-05

  The invention features 4-((phenoxyalkyl)thio)-phenoxyacetic acids and analogs, compositions containing them, and methods of using them as PPAR modulators to treat or inhibit the progression of, for example, dyslipidemia.

  这项发明涉及4-((苯氧烷基)硫基)-苯氧基乙酸及其类似物，含有它们的组合物，以及将它们用作PPAR调节剂来治疗或抑制例如血脂异常等疾病进展的方法。
• 4-((PHENOXYALKYL)THIO)-PHENOXYACETIC ACIDS AND ANALOGS
  申请人：KUO Gee-Hong

  公开号：US20090131489A1

  公开（公告）日：2009-05-21

  The invention features 4-((phenoxyalkyl)thio)-phenoxyacetic acids and analogs, compositions containing them, and methods of using them as PPAR modulators to treat or inhibit the progression of, for example, dyslipidemia.

  这项发明涉及4-((苯氧烷基)硫基)-苯氧乙酸及其类似物、包含它们的组合物，以及将它们用作PPAR调节剂治疗或抑制例如脂质代谢异常等疾病进展的方法。
• PHENOXYACETIC ACIDS DERIVATIVES USEFUL AS PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR (PPAR) DUAL AGONISTS
  申请人：JANSSEN PHARMACEUTICA N.V.

  公开号：EP1684752B1

  公开（公告）日：2007-05-16
• US7015329B2
  申请人：——

  公开号：US7015329B2

  公开（公告）日：2006-03-21
• US7498351B2
  申请人：——

  公开号：US7498351B2

  公开（公告）日：2009-03-03