4-{4-[(5-Cyano-benzofuran-2-carbonyl)-amino]-phenoxy}-piperidine-1-carboxylic acid tert-butyl ester | 221161-00-8

• 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: 4-{4-[(5-Cyano-benzofuran-2-carbonyl)-amino]-phenoxy}-piperidine-1-carboxylic acid tert-butyl ester
• 英文别名: Tert-butyl 4-[4-[(5-cyano-1-benzofuran-2-carbonyl)amino]phenoxy]piperidine-1-carboxylate
• CAS: 221161-00-8
• 化学式: C₂₆H₂₇N₃O₅
• 分子量: 461.517
• InChiKey: WSRIJNNVTQLKCK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  34
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  105
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-{4-[(5-Cyano-benzofuran-2-carbonyl)-amino]-phenoxy}-piperidine-1-carboxylic acid tert-butyl ester 在 盐酸 、 sodium hydride 、 三乙胺 、 N,N-二甲基甲酰胺 作用下， 以 甲醇 、 乙醇 为溶剂， 反应 73.0h， 生成 ((5-Carbamimidoyl-benzofuran-2-carbonyl)-{4-[1-(1-imino-ethyl)-piperidin-4-yloxy]-phenyl}-amino)-acetic acid ethyl ester; compound with GENERIC INORGANIC NEUTRAL COMPONENT
  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：

  5-氰基-2-苯并[b]呋喃甲酸 、 4-(4-氨基苯氧基)-1-哌啶甲酸叔丁酯 在 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 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 4-{4-[(5-Cyano-benzofuran-2-carbonyl)-amino]-phenoxy}-piperidine-1-carboxylic acid tert-butyl ester
  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