2-(6-hydroxymethyl-2-phenethylaminobenzoimidazol-1-ylmethyl)-6-methylpyridin-3-ol | 857035-24-6

• 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-(6-hydroxymethyl-2-phenethylaminobenzoimidazol-1-ylmethyl)-6-methylpyridin-3-ol
• 英文别名: 2-[[6-(Hydroxymethyl)-2-(2-phenylethylamino)benzimidazol-1-yl]methyl]-6-methylpyridin-3-ol
• CAS: 857035-24-6
• 化学式: C₂₃H₂₄N₄O₂
• 分子量: 388.469
• InChiKey: DVGKQLWEUWQPOR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  29
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  83.2
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  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
• 作为产物：
  描述：

  3-(3-hydroxy-6-methylpyridin-2-ylmethyl)-2-phenethylamino-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70%的产率得到2-(6-hydroxymethyl-2-phenethylaminobenzoimidazol-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

文献信息

• Selection of a Respiratory Syncytial Virus Fusion Inhibitor Clinical Candidate. 2. Discovery of a Morpholinopropylaminobenzimidazole Derivative (TMC353121)
  作者：Jean-François Bonfanti、Christophe Meyer、Frédéric Doublet、Jérôme Fortin、Philippe Muller、Laurence Queguiner、Tom Gevers、Peggy Janssens、Heidi Szel、Rudy Willebrords、Philip Timmerman、Koen Wuyts、Pieter van Remoortere、Frans Janssens、Piet Wigerinck、Koen Andries

  DOI：10.1021/jm701284j

  日期：2008.2.1

  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.