4-(4-bromophenyl)-2-(2-carboxybenzoylamino)thiophene-3-carboxylic acid ethyl ester | 312939-81-4

• 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: 4-(4-bromophenyl)-2-(2-carboxybenzoylamino)thiophene-3-carboxylic acid ethyl ester
• 英文别名: 2-{[4-(4-Bromophenyl)-3-(ethoxycarbonyl)thiophen-2-yl]carbamoyl}benzoic acid；2-[[4-(4-bromophenyl)-3-ethoxycarbonylthiophen-2-yl]carbamoyl]benzoic acid
• CAS: 312939-81-4
• 化学式: C₂₁H₁₆BrNO₅S
• 分子量: 474.332
• InChiKey: ZSSVVXQWWRCJQK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  29
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  121
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-(4-bromophenyl)-2-(2-carboxybenzoylamino)thiophene-3-carboxylic acid ethyl ester 、 2-甲氧基苯基硼酸 在 四(三苯基膦)钯 、 四丁基溴化铵 、 sodium carbonate 作用下， 以 水 为溶剂， 反应 0.17h， 以85%的产率得到2-(2-carboxybenzoylamino)-4-(2'-methoxybiphenyl-4-yl)thiophene-3-carboxylic acid ethyl ester
  参考文献：
  名称：

  Novel thiophene derivatives as PTP1B inhibitors with selectivity and cellular activity

  摘要：

  A series of novel thiophene derivatives was designed, synthesized and their activities as competitive inhibitors of protein tyrosine phosphatase (PTPs) 1B (PTP1B) inhibitors were evaluated. All the compounds showed inhibitory potencies, and 10 of these exhibited moderate inhibitory activities with IC50 values less than 10 mu M. The activity of the most potent compound P28 (IC50 = 2.1 mu M) was 15 times higher than that of the hit compound P01. Further, four representative compounds (P19, P22, P28, and P31) demonstrated remarkably high selectivities against other PTPs (e. g., PTP alpha, LAR, CD45, and TCPTP); P19 exhibited greater than sixfold selectivity over highly homologous TCPTP. More importantly, these compounds are permeable to cell membranes. The treatment of CHO-K1 cells with P28 (10 mu M) resulted in increased phosphorylation of AKT, which suggested extensive cellular activity of this compound. The novel chemical entities reported in this study could be used for overcoming the poor selectivity and low cellular activity of PTP1B inhibitors and might represent a starting point for development of therapeutic PTP inhibitors. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.01.055
• 作为产物：
  描述：

  2-氨基-4-(4-溴苯基)-3-噻吩甲酸乙酯 、 苯酐 以 二氯甲烷 为溶剂， 以65%的产率得到4-(4-bromophenyl)-2-(2-carboxybenzoylamino)thiophene-3-carboxylic acid ethyl ester
  参考文献：
  名称：

  Novel thiophene derivatives as PTP1B inhibitors with selectivity and cellular activity

  摘要：

  A series of novel thiophene derivatives was designed, synthesized and their activities as competitive inhibitors of protein tyrosine phosphatase (PTPs) 1B (PTP1B) inhibitors were evaluated. All the compounds showed inhibitory potencies, and 10 of these exhibited moderate inhibitory activities with IC50 values less than 10 mu M. The activity of the most potent compound P28 (IC50 = 2.1 mu M) was 15 times higher than that of the hit compound P01. Further, four representative compounds (P19, P22, P28, and P31) demonstrated remarkably high selectivities against other PTPs (e. g., PTP alpha, LAR, CD45, and TCPTP); P19 exhibited greater than sixfold selectivity over highly homologous TCPTP. More importantly, these compounds are permeable to cell membranes. The treatment of CHO-K1 cells with P28 (10 mu M) resulted in increased phosphorylation of AKT, which suggested extensive cellular activity of this compound. The novel chemical entities reported in this study could be used for overcoming the poor selectivity and low cellular activity of PTP1B inhibitors and might represent a starting point for development of therapeutic PTP inhibitors. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.01.055