tert-butyl 4-(3,4-dichlorophenyl)-4-[3-[4-(2-oxo-3H-benzimidazol-1-yl)piperidin-1-yl]propyl]piperidine-1-carboxylate | 716357-89-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: tert-butyl 4-(3,4-dichlorophenyl)-4-[3-[4-(2-oxo-3H-benzimidazol-1-yl)piperidin-1-yl]propyl]piperidine-1-carboxylate
• CAS: 716357-89-0
• 化学式: C₃₁H₄₀Cl₂N₄O₃
• 分子量: 587.59
• InChiKey: OWURYQDBCNDEQC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.1
• 重原子数：
  40
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  65.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  Tert-butyl 4-(3,4-dichlorophenyl)-4-(3-oxopropyl)piperidine-1-carboxylate 、 4-（2-酮酸-1-苯并咪唑）哌啶 在 三乙酰氧基硼氢化钠 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成 tert-butyl 4-(3,4-dichlorophenyl)-4-[3-[4-(2-oxo-3H-benzimidazol-1-yl)piperidin-1-yl]propyl]piperidine-1-carboxylate
  参考文献：
  名称：

  Discovery of Bioavailable 4,4-Disubstituted Piperidines as Potent Ligands of the Chemokine Receptor 5 and Inhibitors of the Human Immunodeficiency Virus-1

  摘要：

  We describe robust chemical approaches toward putative CCR5 scaffolds designed in our laboratories. Evaluation of analogues in the (125)I-[MIP-1 beta] binding and Ba-L-HOS antiviral assays resulted in the discovery of 64 and 68 in the 4,4-disubstitited piperidine class H, both potent CCR5 ligands (pIC(50) = 8.30 and 9.00, respectively) and HIV-1 inhibitors (pIC(50) = 7.80 and 7.84, respectively, in Ba-L-HOS assay). In addition, 64 and 68 were bioavailable in rodents, establishing them as lead molecules for further optimization toward CCR5 clinical candidates.

  DOI：

  10.1021/jm800598a

文献信息

• US7645771B2
  申请人：——

  公开号：US7645771B2

  公开（公告）日：2010-01-12
• Discovery of Bioavailable 4,4-Disubstituted Piperidines as Potent Ligands of the Chemokine Receptor 5 and Inhibitors of the Human Immunodeficiency Virus-1
  作者：Wieslaw M. Kazmierski、Christopher Aquino、Brian A. Chauder、Felix Deanda、Robert Ferris、Deborah K. Jones-Hertzog、Terrence Kenakin、Cecilia S. Koble、Christian Watson、Pat Wheelan、Hanbiao Yang、Michael Youngman

  DOI：10.1021/jm800598a

  日期：2008.10.23

  We describe robust chemical approaches toward putative CCR5 scaffolds designed in our laboratories. Evaluation of analogues in the (125)I-[MIP-1 beta] binding and Ba-L-HOS antiviral assays resulted in the discovery of 64 and 68 in the 4,4-disubstitited piperidine class H, both potent CCR5 ligands (pIC(50) = 8.30 and 9.00, respectively) and HIV-1 inhibitors (pIC(50) = 7.80 and 7.84, respectively, in Ba-L-HOS assay). In addition, 64 and 68 were bioavailable in rodents, establishing them as lead molecules for further optimization toward CCR5 clinical candidates.