N-[(E)-[1-[(2,3-dichlorophenyl)methyl]benzimidazol-2-yl]methylideneamino]-4-morpholin-4-ylthieno[3,2-d]pyrimidin-2-amine | 1394047-27-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩并嘧啶酮衍生物
• 英文名称: N-[(E)-[1-[(2,3-dichlorophenyl)methyl]benzimidazol-2-yl]methylideneamino]-4-morpholin-4-ylthieno[3,2-d]pyrimidin-2-amine
• CAS: 1394047-27-8
• 化学式: C₂₅H₂₁Cl₂N₇OS
• 分子量: 538.46
• InChiKey: NSTUASUGUDLXGC-CCVNUDIWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  36
• 可旋转键数：
  6
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  109
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  1,2-二氯-3-(氯甲基)苯 在 正丁基锂 、 potassium carbonate 、 溶剂黄146 作用下， 以 四氢呋喃 、 乙醇 、 正己烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.5h， 生成 N-[(E)-[1-[(2,3-dichlorophenyl)methyl]benzimidazol-2-yl]methylideneamino]-4-morpholin-4-ylthieno[3,2-d]pyrimidin-2-amine
  参考文献：
  名称：

  Design, synthesis and 3D-QSAR analysis of novel 2-hydrazinyl-4-morpholinothieno[3,2-d]pyrimidine derivatives as potential antitumor agents

  摘要：

  A series of 2-hydrazinyl-4-morpholinothieno[3,2-d]pyrimidine derivatives were synthesized and evaluated for their cytotoxic activities against five cancer cell lines. Most of them exhibited moderate to significant cytotoxic activities and high-selectivity against one or more cell lines, and nearly all of them had higher potency than positive controls against MDA-MB-231 cell line. The most promising compound 15f showed strong cytotoxic activities against H460, HT-29 and MDA-MB-231 cell lines, which were 1.7- to 66.5-folds more active than 2-(1H-Indazol-4-yl)-6-((4-(methylsulfonyl)-1-piperazinyl)methyl)-4-(4-morpholinyl)thieno[3,2-d]pyrimidine(GDC-0941). To investigate the SARs of thieno[3,2-d]pyrimidine derivatives in more details, CoMFA (q(2) = 0.436, r(2) = 0.937) and CoMSIA (q(2) = 0.706, r(2) = 0.947) models on H460 cell line were established. The generated 3D-QSAR models can be used for further rational design of novel thienopyrimidines as highly potent and selective cytotoxic agents. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.09.002

文献信息

• Design, synthesis and 3D-QSAR analysis of novel 2-hydrazinyl-4-morpholinothieno[3,2-d]pyrimidine derivatives as potential antitumor agents
  作者：Wufu Zhu、Yajing Liu、Xin Zhai、Xiao Wang、Yan Zhu、Di Wu、Hongyu Zhou、Ping Gong、Yanfang Zhao

  DOI：10.1016/j.ejmech.2012.09.002

  日期：2012.11

  A series of 2-hydrazinyl-4-morpholinothieno[3,2-d]pyrimidine derivatives were synthesized and evaluated for their cytotoxic activities against five cancer cell lines. Most of them exhibited moderate to significant cytotoxic activities and high-selectivity against one or more cell lines, and nearly all of them had higher potency than positive controls against MDA-MB-231 cell line. The most promising compound 15f showed strong cytotoxic activities against H460, HT-29 and MDA-MB-231 cell lines, which were 1.7- to 66.5-folds more active than 2-(1H-Indazol-4-yl)-6-((4-(methylsulfonyl)-1-piperazinyl)methyl)-4-(4-morpholinyl)thieno[3,2-d]pyrimidine(GDC-0941). To investigate the SARs of thieno[3,2-d]pyrimidine derivatives in more details, CoMFA (q(2) = 0.436, r(2) = 0.937) and CoMSIA (q(2) = 0.706, r(2) = 0.947) models on H460 cell line were established. The generated 3D-QSAR models can be used for further rational design of novel thienopyrimidines as highly potent and selective cytotoxic agents. (C) 2012 Elsevier Masson SAS. All rights reserved.