methyl 2-(4-chlorophenyl)-2-(3-(4-chlorophenyl)-2,5-dioxo-8-(thiophen-3-ylmethylamino)-2,3-dihydro-1H-benzo[e][1,4]diazepin-4(5H)-yl)acetate | 1345870-47-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: methyl 2-(4-chlorophenyl)-2-(3-(4-chlorophenyl)-2,5-dioxo-8-(thiophen-3-ylmethylamino)-2,3-dihydro-1H-benzo[e][1,4]diazepin-4(5H)-yl)acetate
• CAS: 1345870-47-4
• 化学式: C₂₉H₂₃Cl₂N₃O₄S
• 分子量: 580.491
• InChiKey: BVOXYGUYFZHAII-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.72
• 重原子数：
  39.0
• 可旋转键数：
  7.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  87.74
• 氢给体数：
  2.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  methyl 2-(4-chlorophenyl)-2-(3-(4-chlorophenyl)-2,5-dioxo-8-(thiophen-3-ylmethylamino)-2,3-dihydro-1H-benzo[e][1,4]diazepin-4(5H)-yl)acetate 在 劳森试剂 作用下， 以 甲苯 为溶剂， 反应 4.0h， 以75.3%的产率得到methyl 2-(4-chlorophenyl)-2-(3-(4-chlorophenyl)-5-oxo-8-((thiophen-3-ylmethyl)amino)-2-thioxo-2,3-dihydro-1H-benzo[e][1,4]diazepin-4(5H)-yl)acetate
  参考文献：
  名称：

  Synthesis and biological evaluation of thio-benzodiazepines as novel small molecule inhibitors of the p53–MDM2 protein–protein interaction

  摘要：

  A series of thio-benzodiazepine p53-MDM2 inhibitors were designed and synthesized based on the principle of bioisosterism. Most of the thio-benzodiazepines had nanomolar to micromolar affinity toward MDM2. Particularly, compounds 8a (K-i = 0.52 mu M) and 8f (K-i = 0.32 mu M) showed binding activity comparable to the positive drug nutlin-3a (K-i = 0.23 mu M). Meanwhile, compound 8j exhibited excellent antitumor activity against the U-2 OS human osteosarcoma cell line with an IC50 value of 1.06 mu M, which was about 23 times higher than that of nutlin-3a. The docking model also successfully predicted that this class of compounds mimicked three p53 critical residues binding to MDM2. The thio-benzodiazepines represent a promising class of non-peptide inhibitors of the p53-MDM2 interaction. (C) 2011 Published by Elsevier Masson SAS.

  DOI：

  10.1016/j.ejmech.2011.09.043
• 作为产物：
  描述：

  异氰基环己烯 在 溶剂黄146 、 potassium hydroxide 作用下， 以 甲醇 为溶剂， 反应 16.67h， 生成 methyl 2-(4-chlorophenyl)-2-(3-(4-chlorophenyl)-2,5-dioxo-8-(thiophen-3-ylmethylamino)-2,3-dihydro-1H-benzo[e][1,4]diazepin-4(5H)-yl)acetate
  参考文献：
  名称：

  Synthesis and biological evaluation of thio-benzodiazepines as novel small molecule inhibitors of the p53–MDM2 protein–protein interaction

  摘要：

  A series of thio-benzodiazepine p53-MDM2 inhibitors were designed and synthesized based on the principle of bioisosterism. Most of the thio-benzodiazepines had nanomolar to micromolar affinity toward MDM2. Particularly, compounds 8a (K-i = 0.52 mu M) and 8f (K-i = 0.32 mu M) showed binding activity comparable to the positive drug nutlin-3a (K-i = 0.23 mu M). Meanwhile, compound 8j exhibited excellent antitumor activity against the U-2 OS human osteosarcoma cell line with an IC50 value of 1.06 mu M, which was about 23 times higher than that of nutlin-3a. The docking model also successfully predicted that this class of compounds mimicked three p53 critical residues binding to MDM2. The thio-benzodiazepines represent a promising class of non-peptide inhibitors of the p53-MDM2 interaction. (C) 2011 Published by Elsevier Masson SAS.

  DOI：

  10.1016/j.ejmech.2011.09.043