3-(4-((4-methyl-2-(4-(trifluoromethyl)phenyl)thiazol-5-yl)methoxy)phenyl)propanoic acid

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 苯丙酸
• 英文名称: 3-(4-((4-methyl-2-(4-(trifluoromethyl)phenyl)thiazol-5-yl)methoxy)phenyl)propanoic acid
• 英文别名: 3-[4-({4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl}methoxy)phenyl]propanoic acid；3-{4-[4-Methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethoxy]-phenyl}-propionic acid；3-[4-[[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]methoxy]phenyl]propanoic acid
• 化学式: C₂₁H₁₈F₃NO₃S
• 分子量: 421.44
• InChiKey: MAJOKGVPWQXGOQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  29
• 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：
  87.7
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  4-(三氟甲基)硫代苯甲酰胺 在 lithium hydroxide 、 lithium aluminium tetrahydride 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 48.0h， 生成 3-(4-((4-methyl-2-(4-(trifluoromethyl)phenyl)thiazol-5-yl)methoxy)phenyl)propanoic acid
  参考文献：
  名称：

  Novel selective small molecule agonists for peroxisome proliferator-activated receptor δ (PPARδ)—synthesis and biological activity

  摘要：

  We report the synthesis and biological activity of a new series of small molecule agonists of the human Peroxisome Proliferator-Activated Receptor delta (PPARdelta). Several hits were identified from our original libraries containing lipophilic carboxylic acids. Optimization of these hits by structure-guided design led to 7k (GW501516) and 71 (GW0742), which shows an EC50 Of 1.1 nM against PPARdelta with 1000-fold selectivity over the other human subtypes. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(03)00207-5

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。
• Parallel Chemistry Approach to Identify Novel Nuclear Receptor Ligands Based on the GW0742 Scaffold
  作者：Kelly A. Teske、Ganesha Rai、Premchendar Nandhikonda、Preetpal S. Sidhu、Belaynesh Feleke、Anton Simeonov、Adam Yasgar、Ajit Jadhav、David J. Maloney、Leggy A. Arnold

  DOI：10.1021/acscombsci.7b00066

  日期：2017.10.9

  We describe the parallel synthesis of novel analogs of GW0742, a peroxisome proliferator-activated receptor delta (PPAR delta) agonist For that purpose, modified reaction conditions were applied, such as a solid-phase palladium-catalyzed Suzuki coupling. In addition, tetrazole-based compounds were generated as a bioisostere for carboxylic acid-containing ligand GW0742. The new compounds were investigated for their ability to activate PPAR delta mediated transcription and their cross-reactivity with the vitamin D receptor (VDR), another member of the nuclear receptor superfamily. We identified many potent PPAR delta agonists that were less toxic than GW0742, where similar to 65 of the compounds synthesized exhibited partial PPAR delta activity (23-98%) with EC50 values ranging from 0.007-18.2 mu M. Some ligands, such as compound 32, were more potent inhibitors of VDR-mediated transcription with significantly reduced PPAR delta activity than GW0742, however, none of the ligands were completely selective for VDR inhibition over PPAR delta activation of transcription.
• 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