2-(2-methyl-4-((4-methyl-2-(4-(trifluoromethyl)phenyl)thiazol-5-yl)methoxy)phenoxy)acetic acid | 317318-58-4

• 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-(2-methyl-4-((4-methyl-2-(4-(trifluoromethyl)phenyl)thiazol-5-yl)methoxy)phenoxy)acetic acid
• 英文别名: 2-[2-methyl-4-({4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl}methoxy)phenoxy]acetic acid；2-[2-Methyl-4-[[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]methoxy]phenoxy]acetic acid
• CAS: 317318-58-4
• 化学式: C₂₁H₁₈F₃NO₄S
• 分子量: 437.439
• InChiKey: AMTRKBPBJHCYSM-UHFFFAOYSA-N

物化性质

• 沸点：
  576.1±60.0 °C(Predicted)
• 密度：
  1.352±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  30
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  96.9
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  4-(三氟甲基)硫代苯甲酰胺 在 sodium tetrahydroborate 、 potassium carbonate 、 potassium iodide 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 乙腈 为溶剂， 反应 26.0h， 生成 2-(2-methyl-4-((4-methyl-2-(4-(trifluoromethyl)phenyl)thiazol-5-yl)methoxy)phenoxy)acetic acid
  参考文献：
  名称：

  Discovery of first-in-class thiazole-based dual FFA1/PPARδ agonists as potential anti-diabetic agents

  摘要：

  The free fatty acid receptor 1 (FFA1 or GPR40) and peroxisome proliferator-activated receptor delta (PPAR delta) have attracted a lot of attention due to their role in promoting insulin secretion and sensibility, respectively, which are two major features of diabetes. Therefore, the dual FFA1/PPAR delta agonists would increase insulin secretion and sensibility by FFA1 and PPAR delta activation. In this study, we hybrid FFA1 agonist AM-4668 with PPAR delta agonist GW501516, leading to the identification of orally bioavailable dual agonist 32, which revealed high selectivity over other PPAR delta. Moreover, compound 32 exhibited good pharmacokinetic profiles with high plasma concentration, sustained half-life and low clearance in vivo. During the hypoglycemic test, a dual agonist 32 enhanced the tolerance of ob/ob mice for glucose loading in a dose-dependent manner. Our results suggest that dual FFA1/PPAR delta agonist could be a valuable therapy for type 2 diabetes. (C) 2018 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2018.12.069

文献信息

• Activator of PPAR delta
  申请人：——

  公开号：US20030203947A1

  公开（公告）日：2003-10-30

  Compounds of Formula (I) are disclosed. These compounds include selective activators of human PPAR delta.

  公式（I）的化合物已被披露。这些化合物包括人类PPAR delta的选择性激活剂。
• [EN] THIAZOLE AND OXAZOLE DERIVATIVES AND THEIR PHARMACEUTICAL USE<br/>[FR] DERIVES DE THIAZOL ET D'OXAZOLE ET UTILISATION PHARMACEUTIQUE DE CEUX-CI
  申请人：GLAXO GROUP LTD

  公开号：WO2001000603A1

  公开（公告）日：2001-01-04

  Compounds of Formula (I) are disclosed. These compounds include selective activators of human PPAR delta.

  本发明公开了化学式(I)的化合物。这些化合物包括选择性激活人类PPAR delta的激动剂。
• Compositions and methods for promoting intestinal stem cell and/or non-stem progenitor cell function
  申请人：Whitehead Institute for Biomedical Research

  公开号：US10426757B2

  公开（公告）日：2019-10-01

  Disclosed herein are novel methods and compositions useful for promoting intestinal stem cell function. The methods and compositions are particularly useful for stimulating the proliferation of and/or self-renewal of intestinal stem cells, as well as for minimizing, preventing, or ameliorating cellular damage resulting from incidental or accidental exposure to radiation (e.g., cancer radiation therapy).

  本文公开了有助于促进肠道干细胞功能的新型方法和组合物。这些方法和组合物特别适用于刺激肠道干细胞的增殖和/或自我更新，以及最大限度地减少、预防或改善因偶然或意外暴露于辐射（如癌症放射治疗）而造成的细胞损伤。
• THIAZOLE AND OXAZOLE DERIVATIVES AND THEIR PHARMACEUTICAL USE
  申请人：GLAXO GROUP LIMITED

  公开号：EP1189895A1

  公开（公告）日：2002-03-27
• COMPOSITIONS AND METHODS FOR PROMOTING INTESTINAL STEM CELL AND/OR NON-STEM PROGENITOR CELL FUNCTION
  申请人：Whitehead Institute for Biomedical Research

  公开号：US20170258772A1

  公开（公告）日：2017-09-14

  Disclosed herein are novel methods and compositions useful for promoting intestinal stem cell function. The methods and compositions are particularly useful for stimulating the proliferation of and/or self-renewal of intestinal stem cells, as well as for minimizing, preventing, or ameliorating cellular damage resulting from incidental or accidental exposure to radiation (e.g., cancer radiation therapy).