3-(3-hydroxy-6-methylpyridin-2-ylmethyl)-2-phenethylamino-3H-benzoimidazole-5-carbaldehyde | 1009646-70-1

• 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: 3-(3-hydroxy-6-methylpyridin-2-ylmethyl)-2-phenethylamino-3H-benzoimidazole-5-carbaldehyde
• 英文别名: 3-[(3-Hydroxy-6-methylpyridin-2-yl)methyl]-2-(2-phenylethylamino)benzimidazole-5-carbaldehyde
• CAS: 1009646-70-1
• 化学式: C₂₃H₂₂N₄O₂
• 分子量: 386.453
• InChiKey: PVTPIALYKFZCHR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  29
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  80
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-(3-hydroxy-6-methylpyridin-2-ylmethyl)-2-phenethylamino-3H-benzoimidazole-5-carbaldehyde 、 3,5-二甲基苯胺盐酸盐 在 sodium cyanoborohydride 、 溶剂黄146 作用下， 以 乙腈 为溶剂， 反应 12.0h， 以75.4%的产率得到2-[[6-[(3,5-Dimethylanilino)methyl]-2-(2-phenylethylamino)benzimidazol-1-yl]methyl]-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-(6-hydroxymethyl-2-phenethylaminobenzoimidazol-1-ylmethyl)-6-methylpyridin-3-ol 在 manganese(IV) oxide 作用下， 以 二氯甲烷 为溶剂， 反应 12.0h， 以100%的产率得到3-(3-hydroxy-6-methylpyridin-2-ylmethyl)-2-phenethylamino-3H-benzoimidazole-5-carbaldehyde
  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