5,11-Bis[(4-methoxyphenyl)methyl]-8-methyl-3,5,7,9,11,13-hexazatricyclo[8.3.0.02,6]trideca-1(10),2,6,8,12-pentaen-4-one | 1421053-52-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑二氮卓类
• 英文名称: 5,11-Bis[(4-methoxyphenyl)methyl]-8-methyl-3,5,7,9,11,13-hexazatricyclo[8.3.0.02,6]trideca-1(10),2,6,8,12-pentaen-4-one
• 英文别名: 5,11-bis[(4-methoxyphenyl)methyl]-8-methyl-3,5,7,9,11,13-hexazatricyclo[8.3.0.02,6]trideca-1(10),2,6,8,12-pentaen-4-one
• CAS: 1421053-52-2
• 化学式: C₂₄H₂₂N₆O₃
• 分子量: 442.477
• InChiKey: SXAVIEOFIPNGHZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  33
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  93.7
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  N-(2-amino-1,2-dicyano-vinyl)-formimydic acid ethyl ester 在 硫酸 、 aniline hydrochloride 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 乙醇 、 乙腈 为溶剂， 反应 21.0h， 生成 5,11-Bis[(4-methoxyphenyl)methyl]-8-methyl-3,5,7,9,11,13-hexazatricyclo[8.3.0.02,6]trideca-1(10),2,6,8,12-pentaen-4-one
  参考文献：
  名称：

  Structure-based drug design and potent anti-cancer activity of tricyclic 5:7:5-fused diimidazo[4,5-d:4′,5′-f][1,3]diazepines

  摘要：

  Judicial structural modifications of 5: 7-fused ring-expanded nucleosides (RENs), based on molecular modeling studies with one of its known targets, human RNA helicase (hDDX3), led to the lead, novel, 5:7-5-fused tricyclic heterocycle (1). The latter exhibited promising broad-spectrum in vitro anti-cancer activity against a number of cancer cell lines screened. This paper describes our systematic, albeit limited, structure-activity relationship (SAR) studies on this lead compound, which produced a number of analogs with broad-spectrum in vitro anti-cancer activities against lung, breast, prostate, and ovarian cancer cell lines, in particular compounds 15i, 15j, 15m and 15n which showed IC50 values in submicromolar to micromolar range, and are worthy of further explorations. The SAR data also enabled us to propose a tentative SAR model for future SAR efforts for ultimate realization of optimally active and minimally toxic anti-cancer compounds based on the diimidazo[4,5-d:4',5'-f][1,3]diazepine structural skeleton of the lead compound 1. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.11.050

文献信息

• Structure-based drug design and potent anti-cancer activity of tricyclic 5:7:5-fused diimidazo[4,5-d:4′,5′-f][1,3]diazepines
  作者：Atul Kondaskar、Shilpi Kondaskar、James C. Fishbein、Brandon A. Carter-Cooper、Rena G. Lapidus、Mariola Sadowska、Martin J. Edelman、Ramachandra S. Hosmane

  DOI：10.1016/j.bmc.2012.11.050

  日期：2013.2

  Judicial structural modifications of 5: 7-fused ring-expanded nucleosides (RENs), based on molecular modeling studies with one of its known targets, human RNA helicase (hDDX3), led to the lead, novel, 5:7-5-fused tricyclic heterocycle (1). The latter exhibited promising broad-spectrum in vitro anti-cancer activity against a number of cancer cell lines screened. This paper describes our systematic, albeit limited, structure-activity relationship (SAR) studies on this lead compound, which produced a number of analogs with broad-spectrum in vitro anti-cancer activities against lung, breast, prostate, and ovarian cancer cell lines, in particular compounds 15i, 15j, 15m and 15n which showed IC50 values in submicromolar to micromolar range, and are worthy of further explorations. The SAR data also enabled us to propose a tentative SAR model for future SAR efforts for ultimate realization of optimally active and minimally toxic anti-cancer compounds based on the diimidazo[4,5-d:4',5'-f][1,3]diazepine structural skeleton of the lead compound 1. (C) 2012 Elsevier Ltd. All rights reserved.