N¹-(4-cyanobenzoyl)-N²-(4-methoxybenzoyl)-1,2-benzenediamine | 219519-55-8

• 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: N¹-(4-cyanobenzoyl)-N²-(4-methoxybenzoyl)-1,2-benzenediamine
• 英文别名: 4-cyano-N-{2-[(4-methoxybenzoyl)amino]phenyl}benzamide；N1-(4-cyanobenzoyl)-N2-(4-methyoxybenzoyl)-1,2-benzenediamine；4-cyano-N-[2-[(4-methoxybenzoyl)amino]phenyl]benzamide
• CAS: 219519-55-8
• 化学式: C₂₂H₁₇N₃O₃
• 分子量: 371.395
• InChiKey: LWJZDBSEGSINGW-UHFFFAOYSA-N

物化性质

• 沸点：
  462.9±40.0 °C(Predicted)
• 密度：
  1.31±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  91.2
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N¹-(4-cyanobenzoyl)-N²-(4-methoxybenzoyl)-1,2-benzenediamine 在 吡啶 、 硫化氢 、 三乙胺 作用下， 反应 48.0h， 生成 4-carbamothioyl-N-[2-[(4-methoxybenzoyl)amino]phenyl]benzamide
  参考文献：
  名称：

  Structure-Based Design of Potent, Amidine-Derived Inhibitors of Factor Xa:  Evaluation of Selectivity, Anticoagulant Activity, and Antithrombotic Activity

  摘要：

  To enhance the potency of 1,2-dibenzamidobenzene-derived inhibitors of factor Xa (fXa), an amidine substituent was incorporated on one of the benzoyl side chains to interact with Asp189 in the S1 specificity pocket. Lead molecule 1 was docked into the active site of Ma to facilitate inhibitor design. Subsequently, iterative SAR studies and molecular modeling led to a 1000-fold increase in Ma affinity and a refined model of the new inhibitors in the Ma active site. Strong support for the computational model was achieved through the acquisition of an X-ray crystal structure using thrombin as a surrogate protein. The amidines in this series show high levels of selectivity for the inhibition of Ma relative to other trypsin-like serine proteases. Furthermore, the Ma affinity of compounds in this series (K-ass = 50-500 x 10(6) L/mol) translates effectively into both anticoagulant activity in vitro and antithrombotic activity in vivo.

  DOI：

  10.1021/jm9903287
• 作为产物：
  描述：

  对甲氧基苯甲酰氯 在 palladium on activated charcoal 吡啶 、 氢气 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 39.0h， 生成 N¹-(4-cyanobenzoyl)-N²-(4-methoxybenzoyl)-1,2-benzenediamine
  参考文献：
  名称：

  Synthesis and biological activity of novel 1,2-disubstituted benzene derivatives as factor Xa inhibitors

  摘要：

  Factor Xa (fXa) is a serine protease that plays a pivotal role in the coagulation cascade. High-tbroughput screening of the Yamanouchi compound library yielded lead compound I with the ability to inhibit fXa at micromolar concentrations. To improve its fXa inhibitory activity and its oral anticoagulant activity, the linker between benzamidine and the central benzene ring was modified and a carboxyl group was introduced at the central benzene ring. The resulting compounds 40b (YM-203552), 41a (YM-202054), and 41c (YM-203558) exhibited potent fXa inhibitory activity and oral anticoagulant activity. In particular, YM-203558 exhibited the most potent oral anticoagulant activity, prolonging PT more than 3-fold at 0.5 and 2.0h. Additionally, these compounds showed a high degree of selectivity for other serine proteases. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.11.005

文献信息

• Antithrombotic agents
  申请人：——

  公开号：US20030195223A1

  公开（公告）日：2003-10-16

  This application relates to a compound of formula I (or a prodrug thereof or a pharmaceutically acceptable salt of the compound or prodrug thereof) as defined herein, pharmaceutical compositions thereof, and its use as an inhibitor of factor Xa, as well as a process for its preparation and intermediates therefor.

  本申请涉及公式I的化合物（或其前药或化合物或前药的药学上可接受的盐），其制药组合物及其作为因子Xa抑制剂的用途，以及其制备过程和中间体。