3-chloro-4,5-bis(chloromethyl)-2-thiophenecarboxylic acid | 229343-06-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩类
• 英文名称: 3-chloro-4,5-bis(chloromethyl)-2-thiophenecarboxylic acid
• 英文别名: 3-Chloro-4,5-bis(chloromethyl)thiophene-2-carboxylic acid
• CAS: 229343-06-0
• 化学式: C₇H₅Cl₃O₂S
• 分子量: 259.541
• InChiKey: RXULFDCISSGUDW-UHFFFAOYSA-N

物化性质

• 沸点：
  405.0±45.0 °C(Predicted)
• 密度：
  1.634±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  65.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-chloro-4,5-bis(chloromethyl)-2-thiophenecarboxylic acid 在 吡啶 、 草酰氯 作用下， 以 二氯甲烷 为溶剂， 生成 3-chloro-N-(4-chloro-2-{[(4-chlorophenyl)amino]carbonyl}phenyl)-4,5-bis(chloromethyl)-2-thiophenecarboxamide
  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：

  3-氯噻吩-2-羧酸 、 氯甲基甲基醚 在 四氯化钛 作用下， 以26%的产率得到3-chloro-4,5-bis(chloromethyl)-2-thiophenecarboxylic acid
  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：EP1040108A1

  公开（公告）日：2000-10-04
• US6140351A
  申请人：——

  公开号：US6140351A

  公开（公告）日：2000-10-31
• US6380221B1
  申请人：——

  公开号：US6380221B1

  公开（公告）日：2002-04-30
• US6498185B1
  申请人：——

  公开号：US6498185B1

  公开（公告）日：2002-12-24
• [EN] ORTHO-ANTHRANILAMIDE DERIVATIVES AS ANTI-COAGULANTS<br/>[FR] DERIVES D' DOLLAR I(ORTHO)-ANTHRANILAMIDE COMME ANTICOAGULANTS
  申请人：——

  公开号：WO1999032477A1

  公开（公告）日：1999-07-01

  [EN] This invention is directed to compounds of formula (III) wherein B, C, D, E, R<1>, R<2> and R<3> are disclosed herein. These compounds are disclosed as being useful as anti-coagulants.
  [FR] L'invention concerne des composés de formule (III) dans laquelle B, C, D, E, R<1>, R<2> et R<3> sont représentés. Ces composés sont utiles comme anticoagulants.