3-chloro-N-{3-[4-(4-fluorobenzyl)piperidin-1-yl]propyl}-4-methylaniline dihydrochloride

• 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: 3-chloro-N-{3-[4-(4-fluorobenzyl)piperidin-1-yl]propyl}-4-methylaniline dihydrochloride
• 英文别名: 3-chloro-N-[3-[4-[(4-fluorophenyl)methyl]piperidin-1-yl]propyl]-4-methylaniline;hydrochloride
• 化学式: C₂₂H₂₈ClFN₂*2ClH
• 分子量: 447.851
• InChiKey: AOSACOWYNPRGRW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.97
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  15.3
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-chloro-N-{3-[4-(4-fluorobenzyl)piperidin-1-yl]propyl}-4-methylaniline dihydrochloride 、 1-乙酰基哌啶-4-酰基氯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 1-Acetyl-N-(3-chloro-4-methylphenyl)-N-{3-[4-(4-fluorobenzyl)-1-piperidinyl]propyl}-4-piperidinecarboxamide
  参考文献：
  名称：

  CCR5 antagonists as anti-HIV-1 agents. Part 3: Synthesis and biological evaluation of piperidine-4-carboxamide derivatives

  摘要：

  Replacement of the 5-oxopyrrolidin-3-yl fragment in the previously reported lead structure with a 1-acetylpiperidin-4-yl group led to the discovery of a novel series of potent CCR5 antagonists. Introduction of small hydrophobic substituents on the central phenyl ring increased the binding affinity, providing low to sub-nanomolar CCR5 antagonists. The selected compound 11f showed excellent antiviral activity against CCR5-using HIV-1 replication in human peripheral blood mononuclear cells (EC50 = 0.59 nM) and an acceptable pharmacokinetic profile in dogs. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.10.013

文献信息

• US6562978B1
  申请人：——

  公开号：US6562978B1

  公开（公告）日：2003-05-13
• CCR5 antagonists as anti-HIV-1 agents. Part 3: Synthesis and biological evaluation of piperidine-4-carboxamide derivatives
  作者：Shinichi Imamura、Youichi Nishikawa、Takashi Ichikawa、Taeko Hattori、Yoshihiro Matsushita、Shohei Hashiguchi、Naoyuki Kanzaki、Yuji Iizawa、Masanori Baba、Yoshihiro Sugihara

  DOI：10.1016/j.bmc.2004.10.013

  日期：2005.1

  Replacement of the 5-oxopyrrolidin-3-yl fragment in the previously reported lead structure with a 1-acetylpiperidin-4-yl group led to the discovery of a novel series of potent CCR5 antagonists. Introduction of small hydrophobic substituents on the central phenyl ring increased the binding affinity, providing low to sub-nanomolar CCR5 antagonists. The selected compound 11f showed excellent antiviral activity against CCR5-using HIV-1 replication in human peripheral blood mononuclear cells (EC50 = 0.59 nM) and an acceptable pharmacokinetic profile in dogs. (C) 2004 Elsevier Ltd. All rights reserved.