1-Dimethylcarbamoyl-3-[4-(2-methyl-4-oxo-4,5-dihydro-imidazo[4,5-c]pyridin-1-ylmethyl)-benzoyl]-1H-indole-4-carboxylic acid methyl ester | 170499-10-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 1-Dimethylcarbamoyl-3-[4-(2-methyl-4-oxo-4,5-dihydro-imidazo[4,5-c]pyridin-1-ylmethyl)-benzoyl]-1H-indole-4-carboxylic acid methyl ester
• 英文别名: methyl 1-(dimethylcarbamoyl)-3-[4-[(2-methyl-4-oxo-5H-imidazo[4,5-c]pyridin-1-yl)methyl]benzoyl]indole-4-carboxylate
• CAS: 170499-10-2
• 化学式: C₂₈H₂₅N₅O₅
• 分子量: 511.537
• InChiKey: CJZRHJYAMUYAKM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  38
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  116
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-Dimethylcarbamoyl-3-[4-(2-methyl-4-oxo-4,5-dihydro-imidazo[4,5-c]pyridin-1-ylmethyl)-benzoyl]-1H-indole-4-carboxylic acid methyl ester 在 三氯氧磷 作用下， 反应 1.0h， 以34 mg的产率得到1-N,N-dimethylcarbamoyl-4-methoxycarbonyl-3-{4-[(4-chloro-1H-2-methylimidazo[4.5-c]pyrid-1-yl)methyl]benzoyl}indole
  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：

  4-氯甲基苯甲酰氯 在 N,N-二甲基丙烯基脲 、 乙基溴化镁 、 乙酸酐 、 sodium hydride 、 间氯过氧苯甲酸 、 sodium bromide 、 zinc(II) chloride 作用下， 以 二氯甲烷 为溶剂， 反应 12.5h， 生成 1-Dimethylcarbamoyl-3-[4-(2-methyl-4-oxo-4,5-dihydro-imidazo[4,5-c]pyridin-1-ylmethyl)-benzoyl]-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+