methyl 2-(4-chlorophenyl)-2-(3-(4-chlorophenyl)-8-methoxy-5-oxo-2-thioxo-2,3-dihydro-1H-benzo[e][1,4]diazepin-4(5H)-yl)acetate | 1413931-30-2

• 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)-8-methoxy-5-oxo-2-thioxo-2,3-dihydro-1H-benzo[e][1,4]diazepin-4(5H)-yl)acetate
• 英文别名: Methyl 2-(4-chlorophenyl)-2-[3-(4-chlorophenyl)-8-methoxy-5-oxo-2-sulfanylidene-1,3-dihydro-1,4-benzodiazepin-4-yl]acetate
• CAS: 1413931-30-2
• 化学式: C₂₅H₂₀Cl₂N₂O₄S
• 分子量: 515.417
• InChiKey: SOCGYKSWZHVIGP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  34
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  100
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl 2-(4-chlorophenyl)-2-(3-(4-chlorophenyl)-8-methoxy-5-oxo-2-thioxo-2,3-dihydro-1H-benzo[e][1,4]diazepin-4(5H)-yl)acetate 、 溴乙酸乙酯 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 二氯甲烷 为溶剂， 以90%的产率得到methyl 2-(4-chlorophenyl)-2-(3-(4-chlorophenyl)-2-((2-ethoxy-2-oxoethyl) thio)-8-methoxy-5-oxo-3H-benzo[e][1,4]diazepin-4(5H)-yl)acetate
  参考文献：
  名称：

  Structure–activity relationship and antitumor activity of thio-benzodiazepines as p53–MDM2 protein–protein interaction inhibitors

  摘要：

  In order to discuss the structure activity relationship (SAR) of the thio-benzodiazepine compounds which showed excellent activity against p53-MDM2 protein-protein interaction, we designed and synthesized twenty compounds with electrophilic and nucleophilic groups on the benzene ring. Among them, compounds 8i (K-i = 91 nM) and 8n (K-i = 89 nM) showed better binding activity than that of the reference drug Nutlin-3a (K-i = 121 nM). In addition, in vitro antitumor activity against Saos-2, U-2 OS, A549 and NCI-H1299 cell-lines were assayed by the MTT method. Especially, compounds 8i and 8n possessed excellent biological activity and good selectivity comparable to Nutlin-3a, which were promising candidates for further evaluation. (c) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.08.003
• 作为产物：
  描述：

  在 劳森试剂 、 铁粉 作用下， 以 溶剂黄146 、 甲苯 为溶剂， 反应 5.0h， 生成 methyl 2-(4-chlorophenyl)-2-(3-(4-chlorophenyl)-8-methoxy-5-oxo-2-thioxo-2,3-dihydro-1H-benzo[e][1,4]diazepin-4(5H)-yl)acetate
  参考文献：
  名称：

  Structure–activity relationship and antitumor activity of thio-benzodiazepines as p53–MDM2 protein–protein interaction inhibitors

  摘要：

  In order to discuss the structure activity relationship (SAR) of the thio-benzodiazepine compounds which showed excellent activity against p53-MDM2 protein-protein interaction, we designed and synthesized twenty compounds with electrophilic and nucleophilic groups on the benzene ring. Among them, compounds 8i (K-i = 91 nM) and 8n (K-i = 89 nM) showed better binding activity than that of the reference drug Nutlin-3a (K-i = 121 nM). In addition, in vitro antitumor activity against Saos-2, U-2 OS, A549 and NCI-H1299 cell-lines were assayed by the MTT method. Especially, compounds 8i and 8n possessed excellent biological activity and good selectivity comparable to Nutlin-3a, which were promising candidates for further evaluation. (c) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.08.003