tert-butyl 4-(2-(4-iodo-2-methoxypyridin-3-yl)-4-methyl-1H-benzo[d]imidazol-6-yl)piperidine-1-carboxylate | 1054315-50-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: tert-butyl 4-(2-(4-iodo-2-methoxypyridin-3-yl)-4-methyl-1H-benzo[d]imidazol-6-yl)piperidine-1-carboxylate
• 英文别名: tert-butyl 4-[2-(4-iodo-2-methoxypyridin-3-yl)-7-methyl-3H-benzimidazol-5-yl]piperidine-1-carboxylate
• CAS: 1054315-50-2
• 化学式: C₂₄H₂₉IN₄O₃
• 分子量: 548.424
• InChiKey: NQXUWCDEUPBPAO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  32
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  80.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-(2-(4-iodo-2-methoxypyridin-3-yl)-4-methyl-1H-benzo[d]imidazol-6-yl)piperidine-1-carboxylate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 生成 2-(4-iodo-2-methoxypyridin-3-yl)-4-methyl-(piperidin-4-yl)-1H-benzo[d]imidazole
  参考文献：
  名称：

  Discovery and Evaluation of 4-(2-(4-chloro-1H-pyrazol-1-yl)ethylamino)-3-(6-(1-(3-fluoropropyl)piperidin-4-yl)-4-methyl-1H-benzo[d]imidazol-2-yl)pyridin-2(1H)-one (BMS-695735), an Orally Efficacious Inhibitor of Insulin-like Growth Factor-1 Receptor Kinase with Broad Spectrum in Vivo Antitumor Activity

  摘要：

  We previously reported that 1 (BMS-536924), a benzimidazole inhibitor of the insulin-like growth factor-1 receptor, had demonstrated in vivo antitumor activity. This lead compound was found to have potent CYP3A4 inhibition, CYP3A4 induction mediated by PXR transactivation, poor aqueous solubility, and high plasma protein binding. Herein we disclose the evolution of this chemotype to address these issues. This effort led to 10 (BMS-695735), which exhibits improved ADME properties, a low risk for drug-drug interactions, and in vivo efficacy in multiple xenograft models.

  DOI：

  10.1021/jm800832q
• 作为产物：
  描述：

  tert-butyl 4-(3,4-diamino-5-methylphenyl)piperidine-1-carboxylate 、 4-碘-2-甲氧基吡啶-3-甲醛 以 甲醇 为溶剂， 反应 14.0h， 以9 g的产率得到tert-butyl 4-(2-(4-iodo-2-methoxypyridin-3-yl)-4-methyl-1H-benzo[d]imidazol-6-yl)piperidine-1-carboxylate
  参考文献：
  名称：

  Discovery and Evaluation of 4-(2-(4-chloro-1H-pyrazol-1-yl)ethylamino)-3-(6-(1-(3-fluoropropyl)piperidin-4-yl)-4-methyl-1H-benzo[d]imidazol-2-yl)pyridin-2(1H)-one (BMS-695735), an Orally Efficacious Inhibitor of Insulin-like Growth Factor-1 Receptor Kinase with Broad Spectrum in Vivo Antitumor Activity

  摘要：

  We previously reported that 1 (BMS-536924), a benzimidazole inhibitor of the insulin-like growth factor-1 receptor, had demonstrated in vivo antitumor activity. This lead compound was found to have potent CYP3A4 inhibition, CYP3A4 induction mediated by PXR transactivation, poor aqueous solubility, and high plasma protein binding. Herein we disclose the evolution of this chemotype to address these issues. This effort led to 10 (BMS-695735), which exhibits improved ADME properties, a low risk for drug-drug interactions, and in vivo efficacy in multiple xenograft models.

  DOI：

  10.1021/jm800832q