(S)-4-(2-(2-(4-(benzyloxy)phenyl)-1-(cyclohexanecarboxamido)ethyl)thiazole-4-carboxamido)benzoic acid | 1489277-81-7

• 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: (S)-4-(2-(2-(4-(benzyloxy)phenyl)-1-(cyclohexanecarboxamido)ethyl)thiazole-4-carboxamido)benzoic acid
• 英文别名: 4-[[2-[(1S)-1-(cyclohexanecarbonylamino)-2-(4-phenylmethoxyphenyl)ethyl]-1,3-thiazole-4-carbonyl]amino]benzoic acid
• CAS: 1489277-81-7
• 化学式: C₃₃H₃₃N₃O₅S
• 分子量: 583.708
• InChiKey: CUHDBPAZECNDLA-NDEPHWFRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.3
• 重原子数：
  42
• 可旋转键数：
  11
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  146
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  (S)-methyl 4-(2-(2-(4-(benzyloxy)phenyl)-1-(cyclohexanecarboxamido)ethyl)thiazole-4-carboxamido)benzoate 在 lithium hydroxide monohydrate 作用下， 以 1,4-二氧六环 、 水 为溶剂， 以92%的产率得到(S)-4-(2-(2-(4-(benzyloxy)phenyl)-1-(cyclohexanecarboxamido)ethyl)thiazole-4-carboxamido)benzoic acid
  参考文献：
  名称：

  Design, synthesis, and biological evaluation of novel 2-ethyl-5-phenylthiazole-4-carboxamide derivatives as protein tyrosine phosphatase 1B inhibitors with improved cellular efficacy

  摘要：

  Protein tyrosine phosphatase 1B (PTP1B) is implicated as a key negative regulator of the insulin and leptin signal-transduction pathways. PTP1B inhibitors have emerged as attractive and potent pharmaceutical agents for the treatment of type 2 diabetes and obesity. We identified a series of 2-ethy1-5-phenylthiazole-4-carboxamide (PTA) derivatives, inspired from the ACT scaffold of Scleritodermin A, as a novel class of PTP1B inhibitors. Structure-activity relationship (SAR) analysis and docking studies revealed the molecular basis of PTP1B inhibition by these compounds. PTA derivative 18g was capable of inhibiting intracellular PTP1B and subsequently activating the insulin signaling pathway. Treatment of cells with 18g markedly increased the phosphorylation levels of IRP and Akt as well as the rate of glucose uptake. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.09.017

文献信息

• Design, synthesis, and biological evaluation of novel 2-ethyl-5-phenylthiazole-4-carboxamide derivatives as protein tyrosine phosphatase 1B inhibitors with improved cellular efficacy
  作者：Yue-Ting Chen、Chun-Lan Tang、Wei-Ping Ma、Li-Xin Gao、Yi Wei、Wei Zhang、Jing-Ya Li、Jia Li、Fa-Jun Nan

  DOI：10.1016/j.ejmech.2013.09.017

  日期：2013.11

  Protein tyrosine phosphatase 1B (PTP1B) is implicated as a key negative regulator of the insulin and leptin signal-transduction pathways. PTP1B inhibitors have emerged as attractive and potent pharmaceutical agents for the treatment of type 2 diabetes and obesity. We identified a series of 2-ethy1-5-phenylthiazole-4-carboxamide (PTA) derivatives, inspired from the ACT scaffold of Scleritodermin A, as a novel class of PTP1B inhibitors. Structure-activity relationship (SAR) analysis and docking studies revealed the molecular basis of PTP1B inhibition by these compounds. PTA derivative 18g was capable of inhibiting intracellular PTP1B and subsequently activating the insulin signaling pathway. Treatment of cells with 18g markedly increased the phosphorylation levels of IRP and Akt as well as the rate of glucose uptake. (C) 2013 Elsevier Masson SAS. All rights reserved.