3-{4-[(3-Amino-pyridin-4-ylamino)-methyl]-cyclohexanecarbonyl}-1-dimethylcarbamoyl-1H-indole-4-carboxylic acid methyl ester | 183283-82-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 3-{4-[(3-Amino-pyridin-4-ylamino)-methyl]-cyclohexanecarbonyl}-1-dimethylcarbamoyl-1H-indole-4-carboxylic acid methyl ester
• CAS: 183283-82-1
• 化学式: C₂₆H₃₁N₅O₄
• 分子量: 477.563
• InChiKey: BJCGUHNPRJSECJ-QAQDUYKDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.04
• 重原子数：
  35.0
• 可旋转键数：
  6.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  119.55
• 氢给体数：
  2.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  乙酸酐 、 3-{4-[(3-Amino-pyridin-4-ylamino)-methyl]-cyclohexanecarbonyl}-1-dimethylcarbamoyl-1H-indole-4-carboxylic acid methyl ester 在 溶剂黄146 作用下， 反应 2.0h， 生成
  参考文献：
  名称：

  Discovery and Evaluation of a Series of 3-Acylindole Imidazopyridine Platelet-Activating Factor Antagonists

  摘要：

  Studies conducted with the goal of discovering a second-generation platelet-activating factor (PAF) antagonist have identified a novel class of potent and orally active antagonists which have high aqueous solubility and long duration of action in animal models. The compounds arose from the combination of the lipophilic indole portion of Abbott's first-generation PAF antagonist ABT-299 (2) with the methylimidazopyridine heterocycle moiety of British Biotechnology's BB-882 (1) and possess the positive attributes of both of these clinical candidates. Structure-activity relationship (SAR) studies indicated that modification of the indole and benzoyl spacer of lead compound 7b gave analogues that were more potent, longer-lived, and bioavailable and resulted in the identification of 1-(N,N-dimethylcarbamoyl)-4-ethynyl-3-(3-fluoro-4-[(1H-2-methylimidazo[4,5-c]pyrid-1-yl)methyl] benzoyl}indole hydrochloride (ABT-491, 22m.HCl) which has been evaluated extensively and is currently in clinical development.

  DOI：

  10.1021/jm970389+
• 作为产物：
  描述：

  trans-4-(N-carbobenzyloxy)aminomethyl-1-cyclohexane carbonyl chloride 在 palladium on activated charcoal 氢氧化钾 、 乙基溴化镁 、 氢气 、 zinc(II) chloride 作用下， 以 甲醇 、 乙醇 为溶剂， 25.0 ℃ 、405.3 kPa 条件下， 反应 21.25h， 生成 3-{4-[(3-Amino-pyridin-4-ylamino)-methyl]-cyclohexanecarbonyl}-1-dimethylcarbamoyl-1H-indole-4-carboxylic acid methyl ester
  参考文献：
  名称：

  Discovery and Evaluation of a Series of 3-Acylindole Imidazopyridine Platelet-Activating Factor Antagonists

  摘要：

  Studies conducted with the goal of discovering a second-generation platelet-activating factor (PAF) antagonist have identified a novel class of potent and orally active antagonists which have high aqueous solubility and long duration of action in animal models. The compounds arose from the combination of the lipophilic indole portion of Abbott's first-generation PAF antagonist ABT-299 (2) with the methylimidazopyridine heterocycle moiety of British Biotechnology's BB-882 (1) and possess the positive attributes of both of these clinical candidates. Structure-activity relationship (SAR) studies indicated that modification of the indole and benzoyl spacer of lead compound 7b gave analogues that were more potent, longer-lived, and bioavailable and resulted in the identification of 1-(N,N-dimethylcarbamoyl)-4-ethynyl-3-(3-fluoro-4-[(1H-2-methylimidazo[4,5-c]pyrid-1-yl)methyl] benzoyl}indole hydrochloride (ABT-491, 22m.HCl) which has been evaluated extensively and is currently in clinical development.

  DOI：

  10.1021/jm970389+