4-{[2-(4-trifluoromethylphenylimino)-5-(naphthalen-2-ylmethylidene)-4-oxo-3-thiazolidinyl]methyl}benzoic acid

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 4-{[2-(4-trifluoromethylphenylimino)-5-(naphthalen-2-ylmethylidene)-4-oxo-3-thiazolidinyl]methyl}benzoic acid
• 英文别名: 4-[[(5Z)-5-(naphthalen-2-ylmethylidene)-4-oxo-2-[4-(trifluoromethyl)phenyl]imino-1,3-thiazolidin-3-yl]methyl]benzoic acid
• 化学式: C₂₉H₁₉F₃N₂O₃S
• 分子量: 532.543
• InChiKey: XQGXOXVSAUAUSH-WUWWORNJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.4
• 重原子数：
  38
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  95.3
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  4-氨甲基苯甲酸 在 哌啶 、 三乙胺 作用下， 以 乙醇 为溶剂， 反应 48.5h， 生成 4-{[2-(4-trifluoromethylphenylimino)-5-(naphthalen-2-ylmethylidene)-4-oxo-3-thiazolidinyl]methyl}benzoic acid
  参考文献：
  名称：

  New 4-[(5-arylidene-2-arylimino-4-oxo-3-thiazolidinyl)methyl]benzoic acids active as protein tyrosine phosphatase inhibitors endowed with insulinomimetic effect on mouse C2C12 skeletal muscle cells

  摘要：

  In pursuing our research targeting the identification of potent inhibitors of PTP1B and LMW-PTP, we have identified new 4-[(5-arylidene-2-arylimino-4-oxo-3-thiazolidinyl)methyl]benzoic acids endowed with interesting in vitro inhibitory profiles. Most compounds proved to be inhibitors of PTP1B and LMW-PTP isoform IF1. The tested inhibitors also showed selectivity towards PTP1B over the closely related TC-PTP. These compounds were found to activate the insulin-mediated signalling on mouse C2C12 skeletal muscle cells by increasing the phosphorylation levels of the insulin receptor and promoting cellular 2-deoxyglucose uptake.Interestingly, 4-{[5-(4-benzyloxybenzylidene)-2-(4-trifluoromethylphenylmino)-4-oxo-3-thiazolidinyl]methyl}benzoic acid (7d), the best in vitro inhibitor of PTP1B and the isoform IF1 of LMW-PTP, provided the highest activation level of the insulin receptor and was found to be endowed with an excellent insulinomimetic effect on the selected cells. This compound therefore represents an interesting lead compound for developing novel PTP1B and LMW-PTP inhibitors which could be achieved by improving both its pharmacological profile and its potentiating effects on insulin signalling. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.02.012

文献信息

• New 4-[(5-arylidene-2-arylimino-4-oxo-3-thiazolidinyl)methyl]benzoic acids active as protein tyrosine phosphatase inhibitors endowed with insulinomimetic effect on mouse C2C12 skeletal muscle cells
  作者：Rosaria Ottanà、Rosanna Maccari、Simona Amuso、Gerhard Wolber、Daniela Schuster、Sonja Herdlinger、Giampaolo Manao、Guido Camici、Paolo Paoli

  DOI：10.1016/j.ejmech.2012.02.012

  日期：2012.4

  In pursuing our research targeting the identification of potent inhibitors of PTP1B and LMW-PTP, we have identified new 4-[(5-arylidene-2-arylimino-4-oxo-3-thiazolidinyl)methyl]benzoic acids endowed with interesting in vitro inhibitory profiles. Most compounds proved to be inhibitors of PTP1B and LMW-PTP isoform IF1. The tested inhibitors also showed selectivity towards PTP1B over the closely related TC-PTP. These compounds were found to activate the insulin-mediated signalling on mouse C2C12 skeletal muscle cells by increasing the phosphorylation levels of the insulin receptor and promoting cellular 2-deoxyglucose uptake.Interestingly, 4-[5-(4-benzyloxybenzylidene)-2-(4-trifluoromethylphenylmino)-4-oxo-3-thiazolidinyl]methyl}benzoic acid (7d), the best in vitro inhibitor of PTP1B and the isoform IF1 of LMW-PTP, provided the highest activation level of the insulin receptor and was found to be endowed with an excellent insulinomimetic effect on the selected cells. This compound therefore represents an interesting lead compound for developing novel PTP1B and LMW-PTP inhibitors which could be achieved by improving both its pharmacological profile and its potentiating effects on insulin signalling. (C) 2012 Elsevier Masson SAS. All rights reserved.