6-(bromomethyl)-3-chloro-N-(4-chloro-2-{[(4-chlorophenyl)amino]carbonyl}phenyl)benzo[b]thiophene-2-carboxamide | 929021-28-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻吩类
• 英文名称: 6-(bromomethyl)-3-chloro-N-(4-chloro-2-{[(4-chlorophenyl)amino]carbonyl}phenyl)benzo[b]thiophene-2-carboxamide
• CAS: 929021-28-3
• 化学式: C₂₃H₁₄BrCl₃N₂O₂S
• 分子量: 568.705
• InChiKey: CZJPDAGWCVZMNY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.26
• 重原子数：
  32.0
• 可旋转键数：
  5.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.04
• 拓扑面积：
  58.2
• 氢给体数：
  2.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  6-(bromomethyl)-3-chloro-N-(4-chloro-2-{[(4-chlorophenyl)amino]carbonyl}phenyl)benzo[b]thiophene-2-carboxamide 、 盐酸二甲胺 在 Bio-Rad AG₁-X₈ anion exchange resin 作用下， 以 二氯甲烷 为溶剂， 反应 3.5h， 以50%的产率得到N-(4-chlorophenyl)-2-[((3-chloro-6-(dimethylamino)methylbenzo[b]thien-2-yl)carbonyl)amino]-5-chlorobenzamide
  参考文献：
  名称：

  Substituted thiophene-anthranilamides as potent inhibitors of human factor Xa

  摘要：

  A series of thiophene-containing non-amidine factor Xa inhibitors is described. Simple methyl-substituted thiophene analogs were relatively weak inhibitors. However, introduction of hydrophilic substituents at C-4 or C-5 of the thiophene afforded inhibitors with low nanomolar potency. Optimization of the thiophene substituent at C-4 afforded subnanomolar inhibitors with improved in vitro anticoagulant activity. Incorporating basic amine substituents on the thiophene increased hydrophilicity and improved anticoagulant activity. The pharmacokinetic profile of one inhibitor was evaluated in dogs, and the X-ray crystal structure of this compound bound to factor Xa provides insight into the observed SAR for binding to factor Xa. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.12.019
• 作为产物：
  描述：

  2-amino-5-chloro-N-(4-chlorophenyl)benzamide 在 吡啶 、 N-溴代丁二酰亚胺(NBS) 、 过氧化苯甲酰 作用下， 以 苯 为溶剂， 反应 28.0h， 生成 6-(bromomethyl)-3-chloro-N-(4-chloro-2-{[(4-chlorophenyl)amino]carbonyl}phenyl)benzo[b]thiophene-2-carboxamide
  参考文献：
  名称：

  Substituted thiophene-anthranilamides as potent inhibitors of human factor Xa

  摘要：

  A series of thiophene-containing non-amidine factor Xa inhibitors is described. Simple methyl-substituted thiophene analogs were relatively weak inhibitors. However, introduction of hydrophilic substituents at C-4 or C-5 of the thiophene afforded inhibitors with low nanomolar potency. Optimization of the thiophene substituent at C-4 afforded subnanomolar inhibitors with improved in vitro anticoagulant activity. Incorporating basic amine substituents on the thiophene increased hydrophilicity and improved anticoagulant activity. The pharmacokinetic profile of one inhibitor was evaluated in dogs, and the X-ray crystal structure of this compound bound to factor Xa provides insight into the observed SAR for binding to factor Xa. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.12.019