t-butyl 4-(4-chloro-3-fluorophenyl)-4-{2-[3-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo [3.2.1]oct-8-yl]ethyl}piperidine-1-carboxylate | 716359-57-8

• 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: t-butyl 4-(4-chloro-3-fluorophenyl)-4-{2-[3-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo [3.2.1]oct-8-yl]ethyl}piperidine-1-carboxylate
• 英文别名: tert-butyl 4-(4-chloro-3-fluorophenyl)-4-{2-[3-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo [3.2.1]oct-8-yl]ethyl}piperidine-1-carboxylate
• CAS: 716359-57-8
• 化学式: C₃₃H₄₂ClFN₄O₂
• 分子量: 581.173
• InChiKey: DQADNVIXKXGDRN-GPOLMCQNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.66
• 重原子数：
  41.0
• 可旋转键数：
  5.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  50.6
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  t-butyl 4-(4-chloro-3-fluorophenyl)-4-{2-[3-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo [3.2.1]oct-8-yl]ethyl}piperidine-1-carboxylate 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 反应 0.25h， 以100%的产率得到1-(8-{2-[4-(3-ethoxyphenyl)piperidin-4-yl]ethyl}-8-azabicyclo[3.2.1]oct-3-yl)-2-methyl-1H-benzimidazole dihydrochloride
  参考文献：
  名称：

  Novel 4,4-Disubstituted Piperidine-Based C–C Chemokine Receptor-5 Inhibitors with High Potency against Human Immunodeficiency Virus-1 and an Improved human Ether-a-go-go Related Gene (hERG) Profile

  摘要：

  We recently described (J. Med. Chem. 2008, 51, 6538-6546) a novel class of CCR5 antagonists with strong anti-HIV potency. Herein, we detail SAR converting leads 1 and 2 to druglike molecules. The pivotal structural motif enabling this transition was the secondary sulfonamide substituent. Further fine-tuning of the substituent pattern in the sulfonamide paved the way to enhancing potency and bioavailability and minimizing hERG inhibition, resulting in discovery of clinical compound 122 (GSK163929).

  DOI：

  10.1021/jm200279v
• 作为产物：
  描述：

  4-(1-氰基-2-乙氧基-2-氧代亚乙基)-1-哌啶羧酸-1,1-二甲基乙酯 在 copper(I) oxide 、 水 、 三乙酰氧基硼氢化钠 、 二异丁基氢化铝 、 magnesium 、 三乙胺 、 sodium hydroxide 作用下， 以 乙醚 、 乙醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 9.5h， 生成 t-butyl 4-(4-chloro-3-fluorophenyl)-4-{2-[3-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo [3.2.1]oct-8-yl]ethyl}piperidine-1-carboxylate
  参考文献：
  名称：

  Novel 4,4-Disubstituted Piperidine-Based C–C Chemokine Receptor-5 Inhibitors with High Potency against Human Immunodeficiency Virus-1 and an Improved human Ether-a-go-go Related Gene (hERG) Profile

  摘要：

  We recently described (J. Med. Chem. 2008, 51, 6538-6546) a novel class of CCR5 antagonists with strong anti-HIV potency. Herein, we detail SAR converting leads 1 and 2 to druglike molecules. The pivotal structural motif enabling this transition was the secondary sulfonamide substituent. Further fine-tuning of the substituent pattern in the sulfonamide paved the way to enhancing potency and bioavailability and minimizing hERG inhibition, resulting in discovery of clinical compound 122 (GSK163929).

  DOI：

  10.1021/jm200279v