2-butylamino-3-(3-hydroxy-6-methylpyridin-2-ylmethyl)-3H-benzoimidazole-5-carboxylic acid ethyl ester | 1009646-62-1

• 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: 2-butylamino-3-(3-hydroxy-6-methylpyridin-2-ylmethyl)-3H-benzoimidazole-5-carboxylic acid ethyl ester
• 英文别名: Ethyl 2-(butylamino)-3-[(3-hydroxy-6-methylpyridin-2-yl)methyl]benzimidazole-5-carboxylate
• CAS: 1009646-62-1
• 化学式: C₂₁H₂₆N₄O₃
• 分子量: 382.462
• InChiKey: BAIBNDSUJPOFMD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  28
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  89.3
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-butylamino-3-(3-hydroxy-6-methylpyridin-2-ylmethyl)-3H-benzoimidazole-5-carboxylic acid ethyl ester 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 12.0h， 以100%的产率得到2-(2-butylamino-6-hydroxymethylbenzoimidazol-1-ylmethyl)-6-methylpyridin-3-ol
  参考文献：
  名称：

  Selection of a Respiratory Syncytial Virus Fusion Inhibitor Clinical Candidate. 2. Discovery of a Morpholinopropylaminobenzimidazole Derivative (TMC353121)

  摘要：

  A preceding paper (Bonfanti et al. J. Med Chem. 2007, 50, 4572-4584) reported the optimization of the pharmacokinetic profile of substituted benzimidazoles by reducing their tissue retention. However, the modifications that were necessary to achieve this goal also led to a significant drop in anti-RSV activity. This paper describes a molecular modeling study followed by a lead optimization program that led to the recovery of the initial potent antiviral activity and the selection of TMC353121 as a clinical candidate.

  DOI：

  10.1021/jm701284j
• 作为产物：
  描述：

  2-丁基氨基-3H-苯并咪唑-5-羧酸乙酯 、 2-(氯甲基)-6-甲基吡啶-3-醇盐酸盐 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 反应 24.0h， 以23.7%的产率得到2-butylamino-1-(3-hydroxy-6-methylpyridin-2-ylmethyl)-1H-benzoimidazole-5-carboxylic acid ethyl ester
  参考文献：
  名称：

  Selection of a Respiratory Syncytial Virus Fusion Inhibitor Clinical Candidate. 2. Discovery of a Morpholinopropylaminobenzimidazole Derivative (TMC353121)

  摘要：

  A preceding paper (Bonfanti et al. J. Med Chem. 2007, 50, 4572-4584) reported the optimization of the pharmacokinetic profile of substituted benzimidazoles by reducing their tissue retention. However, the modifications that were necessary to achieve this goal also led to a significant drop in anti-RSV activity. This paper describes a molecular modeling study followed by a lead optimization program that led to the recovery of the initial potent antiviral activity and the selection of TMC353121 as a clinical candidate.

  DOI：

  10.1021/jm701284j