methyl 2-(8-chloro-3-(4-chlorophenyl)-2,5-dioxo-2,3-dihydro-1H-benzo[e][1,4]diazepin-4(5H)-yl)-2-(4-chlorophenyl)acetate | 1413931-02-8

• 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-(8-chloro-3-(4-chlorophenyl)-2,5-dioxo-2,3-dihydro-1H-benzo[e][1,4]diazepin-4(5H)-yl)-2-(4-chlorophenyl)acetate
• 英文别名: Methyl 2-[8-chloro-3-(4-chlorophenyl)-2,5-dioxo-1,3-dihydro-1,4-benzodiazepin-4-yl]-2-(4-chlorophenyl)acetate；methyl 2-[8-chloro-3-(4-chlorophenyl)-2,5-dioxo-1,3-dihydro-1,4-benzodiazepin-4-yl]-2-(4-chlorophenyl)acetate
• CAS: 1413931-02-8
• 化学式: C₂₄H₁₇Cl₃N₂O₄
• 分子量: 503.769
• InChiKey: NLCGRCPJESPSIQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  33
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  75.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 2-(8-chloro-3-(4-chlorophenyl)-2,5-dioxo-2,3-dihydro-1H-benzo[e][1,4]diazepin-4(5H)-yl)-2-(4-chlorophenyl)acetate 在 劳森试剂 作用下， 以 甲苯 为溶剂， 反应 4.0h， 以62%的产率得到methyl 2-(8-chloro-3-(4-chlorophenyl)-5-oxo-2-thioxo-2,3-dihydro-1H-benzo[e][1,4]diazepin-4(5H)-yl)-2-(4-chlorophenyl)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：

  4-氯-2-硝基苯甲酸 在 铁粉 、 potassium hydroxide 作用下， 以 甲醇 、 溶剂黄146 为溶剂， 反应 25.17h， 生成 methyl 2-(8-chloro-3-(4-chlorophenyl)-2,5-dioxo-2,3-dihydro-1H-benzo[e][1,4]diazepin-4(5H)-yl)-2-(4-chlorophenyl)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