methyl 4-[(N-{4-[(1-tert-butoxycarbonyl-4-piperidyl)oxy]phenyl}-N-(7-cyano-2-naphthoyl)amino)methyl]benzoate | 221160-91-4

• 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: methyl 4-[(N-{4-[(1-tert-butoxycarbonyl-4-piperidyl)oxy]phenyl}-N-(7-cyano-2-naphthoyl)amino)methyl]benzoate
• CAS: 221160-91-4
• 化学式: C₃₇H₃₇N₃O₆
• 分子量: 619.717
• InChiKey: IHZIQXMGSSEQHO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.12
• 重原子数：
  46.0
• 可旋转键数：
  7.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  109.17
• 氢给体数：
  0.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  methyl 4-[(N-{4-[(1-tert-butoxycarbonyl-4-piperidyl)oxy]phenyl}-N-(7-cyano-2-naphthoyl)amino)methyl]benzoate 在 盐酸 、 三乙胺 作用下， 以 甲醇 、 乙醇 、 水 为溶剂， 反应 77.0h， 生成 4-[(N-{4-[(1-acetimidoyl-4-piperidyl)oxy]phenyl}-N-(7-amidino-2-naphthoyl)amino)methyl]benzoic acid dihydrochloride
  参考文献：
  名称：

  Design, synthesis and biological activity of YM-60828 derivatives: potent and orally-Bioavailable factor Xa inhibitors based on naphthoanilide and naphthalensulfonanilide templates

  摘要：

  Factor Xa (FXa) is a serine protease which plays a pivotal role in the coagulation cascade. The inhibition of FXa has received great interest as a potential target for the development of new antithrombotic drug. Herein we describe a series of novel 7-arnidino-2-naphthoanilide and 7-amidino-2-naphthalensulfonanilide derivatives which are potent FXa inhibitors. These scaffolds are rigid and are allowed to adopt an L-shape conformation which was estimated as the active conformation based on a docking study of YM-60828 with FXa. Optimization of the side chain at the central aniline nitrogen of 7-amidino-2-naphthoanilide has led to several potent and orally active FXa inhibitors. 5h (YM-169964), the best compound of these series, showed potent FXa inhibitory activity (IC50 = 3.9 nM) and effectively prolonged prothrombin time by 9.6-fold ex vivo Lit an oral dose of 3 mg/kg in squirrel monkeys. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(02)00106-2
• 作为产物：
  描述：

  7-formylnaphthalene-2-carbonitrile 在 sodium chlorite 、 sodium hydride 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 45.0h， 生成 methyl 4-[(N-{4-[(1-tert-butoxycarbonyl-4-piperidyl)oxy]phenyl}-N-(7-cyano-2-naphthoyl)amino)methyl]benzoate
  参考文献：
  名称：

  Design, synthesis and biological activity of YM-60828 derivatives: potent and orally-Bioavailable factor Xa inhibitors based on naphthoanilide and naphthalensulfonanilide templates

  摘要：

  Factor Xa (FXa) is a serine protease which plays a pivotal role in the coagulation cascade. The inhibition of FXa has received great interest as a potential target for the development of new antithrombotic drug. Herein we describe a series of novel 7-arnidino-2-naphthoanilide and 7-amidino-2-naphthalensulfonanilide derivatives which are potent FXa inhibitors. These scaffolds are rigid and are allowed to adopt an L-shape conformation which was estimated as the active conformation based on a docking study of YM-60828 with FXa. Optimization of the side chain at the central aniline nitrogen of 7-amidino-2-naphthoanilide has led to several potent and orally active FXa inhibitors. 5h (YM-169964), the best compound of these series, showed potent FXa inhibitory activity (IC50 = 3.9 nM) and effectively prolonged prothrombin time by 9.6-fold ex vivo Lit an oral dose of 3 mg/kg in squirrel monkeys. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(02)00106-2