3-chloro-4-(chloromethyl)-2-thiophenecarboxylic acid methyl ester | 229342-83-0

• 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-(chloromethyl)-2-thiophenecarboxylic acid methyl ester
• 英文别名: 2-Methoxycarbonyl-3-chloro4-(chloromethyl)thiophene；methyl 3-chloro-4-(chloromethyl)thiophene-2-carboxylate
• CAS: 229342-83-0
• 化学式: C₇H₆Cl₂O₂S
• 分子量: 225.095
• InChiKey: SPJSZZYNGFHJNN-UHFFFAOYSA-N

物化性质

• 熔点：
  55-56 °C
• 沸点：
  323.4±42.0 °C(Predicted)
• 密度：
  1.438±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  12
• 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：
  54.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-chloro-4-(chloromethyl)-2-thiophenecarboxylic acid methyl ester 在 吡啶 、 sodium hydroxide 、 氯化亚砜 、 溶剂黄146 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 47.0h， 生成 N-(4-chlorophenyl)-2-[((3-chloro-4-((imidazol-1-yl)methyl)thiophen-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：

  3-氨基-4-甲基噻吩-2-甲酸甲酯 在 盐酸 、 磺酰氯 、 sodium nitrite 、 过氧化苯甲酰 作用下， 以 水 为溶剂， 反应 18.0h， 生成 3-chloro-4-(chloromethyl)-2-thiophenecarboxylic acid methyl ester
  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：Berlex Laboratories, Inc.

  公开号：US06498185B1

  公开（公告）日：2002-12-24

  This invention is directed to compounds of formula (III): wherein B, C, D, E, R1, R2 and R3 are disclosed herein. These compounds are disclosed as being useful as anti coagulants.

  本发明涉及式（III）化合物：其中B，C，D，E，R1，R2和R3在此披露。这些化合物被披露为有用的抗凝剂。
• 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