5-[(4-Fluorophenyl)methyl]-11-[(4-methoxyphenyl)methyl]-3,5,7,9,11,13-hexazatricyclo[8.3.0.02,6]trideca-1(10),2,6,8,12-pentaen-4-one | 1261167-91-2

• 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-[(4-Fluorophenyl)methyl]-11-[(4-methoxyphenyl)methyl]-3,5,7,9,11,13-hexazatricyclo[8.3.0.02,6]trideca-1(10),2,6,8,12-pentaen-4-one
• CAS: 1261167-91-2
• 化学式: C₂₂H₁₇FN₆O₂
• 分子量: 416.414
• InChiKey: BVEKFUZLHGAROO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  31
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  84.4
• 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 12.0h， 生成 5-[(4-Fluorophenyl)methyl]-11-[(4-methoxyphenyl)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

• Novel, Broad Spectrum Anticancer Agents Containing the Tricyclic 5:7:5-Fused Diimidazodiazepine Ring System
  作者：Atul Kondaskar、Shilpi Kondaskar、Raj Kumar、James C. Fishbein、Nidal Muvarak、Rena G. Lapidus、Mariola Sadowska、Martin J. Edelman、Guus M. Bol、Farhad Vesuna、Venu Raman、Ramachandra S. Hosmane

  DOI：10.1021/ml100281b

  日期：2011.3.10

  Synthesis of a series of novel, broad-spectrum anti-cancer agents containing the tricyclic 5:7:5-fused diimidazo[4,5-d:4',5'-f][1,3]diazepine ring system is reported. Compounds 1, 2, 8, 11, and 12 in the series show promising in vitro antitumor activity with low micromolar IC(50)'s against prostate, lung, breast, and ovarian cancer cell lines. Some notions about structure-activity relationships and

  报道了一系列新颖的，广谱的抗癌药，其中包含三环5：7：5-稠合的二咪唑并[4,5-d：4'，5'-f] [1,3]二氮杂ze环系统。该系列中的化合物1、2、8、11和12显示出有希望的体外抗肿瘤活性，且低微摩尔IC（50）对前列腺癌，肺癌，乳腺癌和卵巢癌细胞系具有抗性。提出了一些关于构效关系和生物活性可能机制的概念。还介绍了使用SCID小鼠对1的初步体内毒性研究。