2-(4-iodo-2-methoxypyridin-3-yl)-4-methyl-(piperidin-4-yl)-1H-benzo[d]imidazole trifluoroacetate | 1182705-59-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 2-(4-iodo-2-methoxypyridin-3-yl)-4-methyl-(piperidin-4-yl)-1H-benzo[d]imidazole trifluoroacetate
• CAS: 1182705-59-4
• 化学式: C₂HF₃O₂*C₁₉H₂₁IN₄O
• 分子量: 562.33
• InChiKey: WIBZCVSUSAOZEH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.65
• 重原子数：
  32.0
• 可旋转键数：
  3.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  100.13
• 氢给体数：
  3.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  2-(4-iodo-2-methoxypyridin-3-yl)-4-methyl-(piperidin-4-yl)-1H-benzo[d]imidazole trifluoroacetate 、 羟乙醛 在 sodium cyanoborohydride 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 2.0h， 以73%的产率得到2-(4-(2-(4-iodo-2-methoxypyridin-3-yl)-4-methyl-1H-benzo[d]imidazol-6-yl)piperidin-1-yl)ethanol
  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