4-Methyl-N1,N2-bis(4-methoxybenzoyl)-1,2-benzenediamine

• 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: 4-Methyl-N1,N2-bis(4-methoxybenzoyl)-1,2-benzenediamine
• 英文别名: 4-Methoxy-N-[2-(4-methoxybenzamido)-5-methylphenyl]benzamide；4-methoxy-N-[2-[(4-methoxybenzoyl)amino]-4-methylphenyl]benzamide
• 化学式: C₂₃H₂₂N₂O₄
• mdl: MFCD01920136
• 分子量: 390.439
• InChiKey: NHLKFMRCCXFZGH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  76.7
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  对甲氧基苯甲酰氯 、 3,4-二氨基甲苯 在 吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 12.0h， 以83%的产率得到4-Methyl-N1,N2-bis(4-methoxybenzoyl)-1,2-benzenediamine
  参考文献：
  名称：

  1,2-Dibenzamidobenzene Inhibitors of Human Factor Xa

  摘要：

  High-throughput screening of a combinatorial library of diamidophenols yielded lead compounds with the ability to inhibit human factor Xa (fXa) at micromolar concentrations (e.g. compound 4, fXa apparent K-ass = 0.64 x 10(6) L/mol). SAR studies in this novel structural series of fXa inhibitors showed that the phenolic hydroxyl group was not essential for activity. The best activity was found in substituted 1,2-dibenzamidobenzenes in which the phenyl group of one benzoyl group (A-ring) was substituted in the 4-position with relatively small lipophilic or polarizable groups such as methoxy, vinyl, or chloro and the phenyl group of the other benzoyl group (B-ring) was substituted in the 4-position with larger lipophilic groups such as tert-butyl or dimethylamino. The central phenyl ring (C-ring) tolerated a wide variety of substituents, but methoxy, methanesulfonamido, hydroxyl, and carboxyl substitution produced slightly higher levels of activity than other substituents when present in combination with favorable B-ring substitution. Methylation of the amide nitrogen atoms was found to greatly decrease activity. Compound 12 is the highest affinity fXa inhibitor in this group of compounds, having fXa apparent K-ass = 25.5 x 10(6) L/mol, about 40x more active than the original lead. This lead series does not show potent inhibition of human thrombin. A model for the binding of these ligands to the fXa active site is proposed. The model is consistent with the observed SAR and can serve to guide future SAR studies.

  DOI：

  10.1021/jm990326m

文献信息

• Antithrombotic agents
  申请人：——

  公开号：US20020120007A1

  公开（公告）日：2002-08-29

  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.

  该申请涉及公式I的化合物（或其前药或其药学上可接受的盐或前药的药物组合物），如本文所定义，其作为因子Xa的抑制剂的用途，以及其制备过程和中间体。
• US6313122B1
  申请人：——

  公开号：US6313122B1

  公开（公告）日：2001-11-06
• US6605626B2
  申请人：——

  公开号：US6605626B2

  公开（公告）日：2003-08-12