dimethyl 2'-formylbiphenyl-2,4-dicarboxylate | 787631-44-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: dimethyl 2'-formylbiphenyl-2,4-dicarboxylate
• 英文别名: 2'-formylbiphenyl-2,4-dicarboxylic acid 4-ethyl ester 2-methyl ester；1-O-ethyl 3-O-methyl 4-(2-formylphenyl)benzene-1,3-dicarboxylate
• CAS: 787631-44-1
• 化学式: C₁₈H₁₆O₅
• 分子量: 312.322
• InChiKey: JEGXPPSTLLAHMP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  23
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  69.7
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  dimethyl 2'-formylbiphenyl-2,4-dicarboxylate 在 indium(III) triflate 、 palladium 10% on activated carbon 、 氢气 、 溶剂黄146 作用下， 以 甲醇 、 乙腈 为溶剂， 70.0 ℃ 、101.33 kPa 条件下， 反应 15.0h， 生成 2'-(6-carbamimidoyl-4-phenyl-1,2,3,4-tetrahydroquinolin-2-yl)biphenyl-2,4-dicarboxylic acid
  参考文献：
  名称：

  Tetrahydroquinoline Derivatives as Potent and Selective Factor XIa Inhibitors

  摘要：

  Antithrombotic agents that are inhibitors of factor XIa (FXIa) have the potential to demonstrate robust efficacy with a low bleeding risk profile. Herein, we describe a series of tetrahydroquinoline (THQ) derivatives as FXIa inhibitors. Compound 1 was identified as a potent and selective tool compound for proof of concept studies. It exhibited excellent antithrombotic efficacy in rabbit thrombosis models and did not prolong bleeding times. This demonstrates proof of concept for the FXIa mechanism in animal models with a reversible, small molecule inhibitor.

  DOI：

  10.1021/jm401670x
• 作为产物：
  描述：

  4-溴-1,3-苯二甲酸二甲酯 、 2-甲酰基苯硼酸 在 potassium phosphate 、 四(三苯基膦)钯 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 以65%的产率得到dimethyl 2'-formylbiphenyl-2,4-dicarboxylate
  参考文献：
  名称：

  Tetrahydroquinoline Derivatives as Potent and Selective Factor XIa Inhibitors

  摘要：

  Antithrombotic agents that are inhibitors of factor XIa (FXIa) have the potential to demonstrate robust efficacy with a low bleeding risk profile. Herein, we describe a series of tetrahydroquinoline (THQ) derivatives as FXIa inhibitors. Compound 1 was identified as a potent and selective tool compound for proof of concept studies. It exhibited excellent antithrombotic efficacy in rabbit thrombosis models and did not prolong bleeding times. This demonstrates proof of concept for the FXIa mechanism in animal models with a reversible, small molecule inhibitor.

  DOI：

  10.1021/jm401670x

文献信息

• Biarylmethyl indolines, indoles and tetrahydroquinolines, useful as serine protease inhibitors
  申请人：——

  公开号：US20040220206A1

  公开（公告）日：2004-11-04

  The present invention provides compounds of Formula (I): 1 or a stereoisomer or pharmaceutically acceptable salt or hydrate form thereof, wherein the variables A, B, L 1 , L 2 , X 1 , X 2 , X 3 , X 4 and W are as defined herein. The compounds of Formula (I) are useful as selective inhibitors of serine protease enzymes of the coagulation cascade and/or contact activation system; for example thrombin, factor Xa, factor XIa, factor IXa, factor VIIa and/or plasma kallikrein. In particular, it relates to compounds that are selective factor XIa inhibitors. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating thromboembolic and/or inflammatory disorders using the same.

  本发明提供了Formula (I)的化合物：1或其立体异构体或药用可接受的盐或水合物形式，其中变量A、B、L1、L2、X1、X2、X3、X4和W如本文所定义。Formula (I)的化合物可作为凝血级联和/或接触激活系统的丝氨酸蛋白酶酶的选择性抑制剂，例如凝血酶、因子Xa、因子XIa、因子IXa、因子VIIa和/或血浆激肽。具体地，涉及具有选择性因子XIa抑制剂的化合物。本发明还涉及包含这些化合物的药物组合物以及使用这些药物组合物治疗血栓栓塞性和/或炎症性疾病的方法。
• BIARYLMETHYL INDOLINES, INDOLES AND TETRAHYDROQUINOLINES, USEFUL AS SERINE PROTEASE INHIBITORS
  申请人：Bristol-Myers Squibb Company

  公开号：EP1633716A2

  公开（公告）日：2006-03-15
• EP1633716A4
  申请人：——

  公开号：EP1633716A4

  公开（公告）日：2008-03-26
• US7129264B2
  申请人：——

  公开号：US7129264B2

  公开（公告）日：2006-10-31
• [EN] BIARYLMETHYL INDOLINES, INDOLES AND TETRAHYDROQUINOLINES, USEFUL AS SERINE PROTEASE INHIBITORS<br/>[FR] BIARYLMETHYL INDOLINES, INDOLES ET TETRAHYDROQUINOLINES UTILES EN TANT QU'INHIBITEURS DE LA SERINE PROTEASE
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2004094372A2

  公开（公告）日：2004-11-04

  The present invention provides compounds of Formula (I) or a stereoisomer or pharmaceutically acceptable salt or hydrate form thereof, wherein the variables A, B, L1, L2, X1, X2, X3, X4 and W are as defined herein. The compounds of Formula (I) are useful as selective inhibitors of serine protease enzymes of the coagulation cascade and/or contact activation system; for example thrombin, factor Xa, factor XIa, factor IXa, factor VIIa and/or plasma kallikrein. In particular, it relates to compounds that are selective factor XIa inhibitors. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating thromboembolic and/or inflammatory disorders using the same.