Ethyl 2-[4-[[3-chloro-2-[[4-chloro-2-[(4-chlorophenyl)carbamoyl]phenyl]carbamoyl]-1-benzothiophen-6-yl]methyl]piperazin-1-yl]acetate | 229341-11-1

• 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: Ethyl 2-[4-[[3-chloro-2-[[4-chloro-2-[(4-chlorophenyl)carbamoyl]phenyl]carbamoyl]-1-benzothiophen-6-yl]methyl]piperazin-1-yl]acetate
• CAS: 229341-11-1
• 化学式: C₃₁H₂₉Cl₃N₄O₄S
• 分子量: 660.021
• InChiKey: MERHIFFGWRQOLI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.3
• 重原子数：
  43
• 可旋转键数：
  10
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  119
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  Ethyl 2-[4-[[3-chloro-2-[[4-chloro-2-[(4-chlorophenyl)carbamoyl]phenyl]carbamoyl]-1-benzothiophen-6-yl]methyl]piperazin-1-yl]acetate 、 三氟乙酸 在 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 1.0h， 以0.027 g的产率得到4-[(3-chloro-2-{[(4-chloro-2-{[(4-chlorophenyl)amino]carbonyl}phenyl)amino]carbonyl}benzo[b]thien-6-yl)methyl]-1-piperazineacetic acid trifluoroacetic acid salt
  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：

  5-氯-2-硝基苯甲酸 在 吡啶 、 N-溴代丁二酰亚胺(NBS) 、 草酰氯 、 三乙胺 、 N,N-二甲基甲酰胺 、 tin(ll) chloride 、 过氧化苯甲酰 作用下， 以 二氯甲烷 、 乙酸乙酯 、 苯 为溶剂， 反应 48.25h， 生成 Ethyl 2-[4-[[3-chloro-2-[[4-chloro-2-[(4-chlorophenyl)carbamoyl]phenyl]carbamoyl]-1-benzothiophen-6-yl]methyl]piperazin-1-yl]acetate
  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

文献信息

• ORTHO-ANTHRANILAMIDE DERIVATIVES AS ANTI-COAGULANTS
  申请人：SCHERING AKTIENGESELLSCHAFT

  公开号：EP1040108B1

  公开（公告）日：2004-02-25
• US6140351A
  申请人：——

  公开号：US6140351A

  公开（公告）日：2000-10-31
• US6498185B1
  申请人：——

  公开号：US6498185B1

  公开（公告）日：2002-12-24
• Substituted thiophene-anthranilamides as potent inhibitors of human factor Xa
  作者：Monica J. Kochanny、Marc Adler、Janice Ewing、Brian D. Griedel、Elena Ho、Rushad Karanjawala、Wheeseong Lee、Dao Lentz、Amy M. Liang、Michael M. Morrissey、Gary B. Phillips、Joseph Post、Karna L. Sacchi、Steven T. Sakata、Babu Subramanyam、Ron Vergona、Janette Walters、Kathy A. White、Marc Whitlow、Bin Ye、Zuchun Zhao、Kenneth J. Shaw

  DOI：10.1016/j.bmc.2006.12.019

  日期：2007.3

  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.