(2-{4-[1-(3-hydroxy-6-methylpyridin-2-ylmethyl)-6-(2-m-tolylethyl)-1H-benzoimidazol-2-ylamino]piperidin-1-yl}ethyl)carbamic acid tert-butyl ester | 1009646-44-9

• 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-{4-[1-(3-hydroxy-6-methylpyridin-2-ylmethyl)-6-(2-m-tolylethyl)-1H-benzoimidazol-2-ylamino]piperidin-1-yl}ethyl)carbamic acid tert-butyl ester
• 英文别名: tert-butyl N-[2-[4-[[1-[(3-hydroxy-6-methylpyridin-2-yl)methyl]-6-[2-(3-methylphenyl)ethyl]benzimidazol-2-yl]amino]piperidin-1-yl]ethyl]carbamate
• CAS: 1009646-44-9
• 化学式: C₃₅H₄₆N₆O₃
• 分子量: 598.789
• InChiKey: GMGNAKVRDVJSNE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  44
• 可旋转键数：
  12
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  105
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (2-{4-[1-(3-hydroxy-6-methylpyridin-2-ylmethyl)-6-(2-m-tolylethyl)-1H-benzoimidazol-2-ylamino]piperidin-1-yl}ethyl)carbamic acid tert-butyl ester 在 盐酸 作用下， 以 异丙醇 为溶剂， 反应 4.0h， 生成 2-[[2-[[1-(2-Aminoethyl)piperidin-4-yl]amino]-6-[2-(3-methylphenyl)ethyl]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-{4-[1-(3-hydroxy-6-methylpyridin-2-ylmethyl)-6-(2-m-tolylvinyl)-1H-benzoimidazol-2-ylamino]piperidin-1-yl}ethyl)carbamic acid tert-butyl ester 在 palladium on activated charcoal 氢气 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 20.0 ℃ 、200.0 kPa 条件下， 反应 4.0h， 以100%的产率得到(2-{4-[1-(3-hydroxy-6-methylpyridin-2-ylmethyl)-6-(2-m-tolylethyl)-1H-benzoimidazol-2-ylamino]piperidin-1-yl}ethyl)carbamic acid tert-butyl 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