Cyclohexyl-{3-[4-(2-methyl-4-phenethyl-2H-pyrazol-3-yl)-piperidin-1-ylmethyl]-4-phenyl-pyrrolidin-1-yl}-acetic acid

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: Cyclohexyl-{3-[4-(2-methyl-4-phenethyl-2H-pyrazol-3-yl)-piperidin-1-ylmethyl]-4-phenyl-pyrrolidin-1-yl}-acetic acid
• 英文别名: (2R)-2-cyclohexyl-2-[(3S,4S)-3-[[4-[2-methyl-4-(2-phenylethyl)pyrazol-3-yl]piperidin-1-yl]methyl]-4-phenylpyrrolidin-1-yl]acetic acid
• 化学式: C₃₆H₄₈N₄O₂
• 分子量: 568.803
• InChiKey: NMBWUFYTQZILMB-VUHKNJSWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  42
• 可旋转键数：
  10
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  61.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-苯基-1-丁基溴 在 palladium dihydroxide 、 palladium on activated charcoal chromium(VI) oxide 、 硫酸 、 硼烷 、 potassium tert-butylate 、 氢气 、 ammonium formate 、 双(三甲基硅烷基)氨基钾 、 三乙酰氧基硼氢化钠 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 甲醇 、 1,2-二氯乙烷 、 甲苯 为溶剂， 生成 Cyclohexyl-{3-[4-(2-methyl-4-phenethyl-2H-pyrazol-3-yl)-piperidin-1-ylmethyl]-4-phenyl-pyrrolidin-1-yl}-acetic acid
  参考文献：
  名称：

  Antagonists of human CCR5 receptor containing 4-(pyrazolyl)piperidine side chains. Part 1: Discovery and SAR study of 4-pyrazolylpiperidine side chains

  摘要：

  Replacement of the flexible connecting chains between the piperidine moiety and an aromatic group in previous CCR5 antagonists with heterocycles, such as pyrazole and isoxazole, provided potent CCR5 antagonists with excellent anti-HIV-1 activity in vitro. SAR studies revealed optimal placement of an unsubstituted nitrogen atom in the heterocycle to be meta to the bond connected to the 4-position of piperidine. Truncation of a benzyl group to a phenyl group afforded compounds with dramatically improved oral bioavailability, albeit with reduced activity. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.12.004

文献信息

• Antagonists of human CCR5 receptor containing 4-(pyrazolyl)piperidine side chains. Part 1: Discovery and SAR study of 4-pyrazolylpiperidine side chains
  作者：Dong-Ming Shen、Min Shu、Sander G. Mills、Kevin T. Chapman、Lorraine Malkowitz、Martin S. Springer、Sandra L. Gould、Julie A. DeMartino、Salvatore J. Siciliano、Gloria Y. Kwei、Anthony Carella、Gwen Carver、Karen Holmes、William A. Schleif、Renee Danzeisen、Daria Hazuda、Joseph Kessler、Janet Lineberger、Michael D. Miller、Emilio A. Emini

  DOI：10.1016/j.bmcl.2003.12.004

  日期：2004.2

  Replacement of the flexible connecting chains between the piperidine moiety and an aromatic group in previous CCR5 antagonists with heterocycles, such as pyrazole and isoxazole, provided potent CCR5 antagonists with excellent anti-HIV-1 activity in vitro. SAR studies revealed optimal placement of an unsubstituted nitrogen atom in the heterocycle to be meta to the bond connected to the 4-position of piperidine. Truncation of a benzyl group to a phenyl group afforded compounds with dramatically improved oral bioavailability, albeit with reduced activity. (C) 2004 Elsevier Ltd. All rights reserved.