2-[[2-[[1-(2-Hydroxy-3,3-dimethyl-butyl)-4-piperidyl]amino]-4-methyl-benzimidazol-1-yl]methyl]-6-methyl-pyridin-3-ol

• 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-[[2-[[1-(2-Hydroxy-3,3-dimethyl-butyl)-4-piperidyl]amino]-4-methyl-benzimidazol-1-yl]methyl]-6-methyl-pyridin-3-ol
• 英文别名: 2-[[2-[[1-(2-hydroxy-3,3-dimethylbutyl)piperidin-4-yl]amino]-4-methylbenzimidazol-1-yl]methyl]-6-methylpyridin-3-ol
• 化学式: C₂₆H₃₇N₅O₂
• 分子量: 451.612
• InChiKey: YPULKFFGNHVHJX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  86.4
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  1-{4-[1-(3-hydroxy-6-methyl-pyridin-2-ylmethyl)-4-methyl-1H-benzoimidazol-2-ylamino]-piperidin-1-yl}-3,3-dimethyl-butan-2-one 在 sodium tetrahydroborate 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 12.0h， 以45%的产率得到2-[[2-[[1-(2-Hydroxy-3,3-dimethyl-butyl)-4-piperidyl]amino]-4-methyl-benzimidazol-1-yl]methyl]-6-methyl-pyridin-3-ol
  参考文献：
  名称：

  Selection of a Respiratory Syncytial Virus Fusion Inhibitor Clinical Candidate, Part 1:  Improving the Pharmacokinetic Profile Using the Structure−Property Relationship

  摘要：

  We previously reported the discovery of substituted benzimidazole fusion inhibitors with nanomolar activity against respiratory syncytial virus (Andries, K.; et al. Antiviral Res. 2003, 60, 209-219). A lead compound of the series was selected for preclinical evaluation. This drug candidate, JNJ-2408068 (formerly R 17059 1, 1), showed long tissue retention times in several species (rat, dog, and monkey), creating cause for concern. We herein describe the optimization program to develop compounds with improved properties in terms of tissue retention. We have identified the aminoethyl-piperidine moiety as being responsible for the long tissue retention time of 1. We have investigated the replacement or the modification of this group, and we suggest that the pK(a) of this part of the molecules influences both the antiviral activity and the pharmacokinetic profile. We were able to identify new respiratory syncytial virus inhibitors with shorter half-lives in lung tissue.

  DOI：

  10.1021/jm070143x