4,5-bis(4-chlorophenyl)-N-cyclopropyl-2-(2-morpholin-4-ylethylcarbamoylamino)thiophene-3-carboxamide | 1436574-40-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩类
• 英文名称: 4,5-bis(4-chlorophenyl)-N-cyclopropyl-2-(2-morpholin-4-ylethylcarbamoylamino)thiophene-3-carboxamide
• CAS: 1436574-40-1
• 化学式: C₂₇H₂₈Cl₂N₄O₃S
• 分子量: 559.516
• InChiKey: YLNONKXANPPJIY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  37
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  111
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  吗啉 、 氯乙基异氰酸酯 、 2-amino-4,5-bis(4-chlorophenyl)-N-cyclopropylthiophene-3-carboxamide 在 三乙胺 作用下， 以 二氯甲烷 、 1,4-二氧六环 为溶剂， 反应 1.0h， 以56%的产率得到4,5-bis(4-chlorophenyl)-N-cyclopropyl-2-(2-morpholin-4-ylethylcarbamoylamino)thiophene-3-carboxamide
  参考文献：
  名称：

  Design, synthesis and biological evaluation of novel 3,4,5-trisubstituted aminothiophenes as inhibitors of p53–MDM2 interaction. Part 1

  摘要：

  A series of 3,4,5-trisubstituted aminothiophenes were designed, synthesized, and evaluated for their p53-MDM2 binding inhibitory potency and anti-proliferation activities against A549 and PC3 tumor cell lines. Fourteen compounds had appreciably improved MDM2 binding affinities than lead compound MCL0527 (3) and a few compounds showed comparable activities to that of Nutlin-3. Meanwhile, most of the 3,4,5-trisubstituted aminothiophenes displayed better or equivalent anti-proliferation activities against wild-type p53 cell line A549 compared to that of Nutlin-3. Over ten compounds exhibited desirable selective profiles of p53 status. Particularly, compounds 9, 16 and 18 displayed 22-, 6- and 22-fold selectivity of p53 status, respectively, much better than that of Nutlin-3 (fourfold). (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.03.061

文献信息

• Design, synthesis and biological evaluation of novel 3,4,5-trisubstituted aminothiophenes as inhibitors of p53–MDM2 interaction. Part 1
  作者：Weisi Wang、Shihao Shangguan、Ni Qiu、Chunqi Hu、Lei Zhang、Yongzhou Hu

  DOI：10.1016/j.bmc.2013.03.061

  日期：2013.6

  A series of 3,4,5-trisubstituted aminothiophenes were designed, synthesized, and evaluated for their p53-MDM2 binding inhibitory potency and anti-proliferation activities against A549 and PC3 tumor cell lines. Fourteen compounds had appreciably improved MDM2 binding affinities than lead compound MCL0527 (3) and a few compounds showed comparable activities to that of Nutlin-3. Meanwhile, most of the 3,4,5-trisubstituted aminothiophenes displayed better or equivalent anti-proliferation activities against wild-type p53 cell line A549 compared to that of Nutlin-3. Over ten compounds exhibited desirable selective profiles of p53 status. Particularly, compounds 9, 16 and 18 displayed 22-, 6- and 22-fold selectivity of p53 status, respectively, much better than that of Nutlin-3 (fourfold). (C) 2013 Elsevier Ltd. All rights reserved.