4-[[3-[4-[(4-Fluorophenyl)methyl]-1-piperidyl]propyl-phenyl-carbamoyl]amino]benzoic acid | 711029-75-3

• 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: 4-[[3-[4-[(4-Fluorophenyl)methyl]-1-piperidyl]propyl-phenyl-carbamoyl]amino]benzoic acid
• 英文别名: 4-[[3-[4-[(4-fluorophenyl)methyl]piperidin-1-yl]propyl-phenylcarbamoyl]amino]benzoic acid
• CAS: 711029-75-3
• 化学式: C₂₉H₃₂FN₃O₃
• 分子量: 489.59
• InChiKey: PCVDQKZLQGSPHX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  36
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  72.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-[[3-[4-[(4-Fluorophenyl)methyl]-1-piperidyl]propyl-phenyl-carbamoyl]amino]benzoic acid 在 三乙胺 氯化铵 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 以77%的产率得到4-[[3-[4-[(4-Fluorophenyl)methyl]-1-piperidyl]propyl-phenyl-carbamoyl]amino]benzamide
  参考文献：
  名称：

  CCR5 antagonists as anti-HIV-1 agents. Part 2: Synthesis and biological evaluation of N-[3-(4-benzylpiperidin-1-yl)propyl]-N,N′-diphenylureas

  摘要：

  We have previously reported the novel lead compound 1a as a CCR5 antagonist for treatment of HIV-1 infection. SAR studies on incorporating various acyl groups as a replacement for the 5-oxopyrrolidine-3-carbonyl group of the lead structure resulted in the discovery of N-[3-(4-benzylpiperidin-1-yl)propyl]-N,N-1-diphenylurea (4a) with significantly improved CCR5 binding affinity. Substitutions (4-Cl, 4e,f; 4-Me, 4i) on the N'-phenyl ring further increased the binding affinity. Introduction of polar substituents on the phenyl ring of the 4-benzylpiperidine moiety enhanced the inhibitory activity of the HIV-1 envelope-mediated membrane fusion (4v,w), suggesting that polar substituents at this position can interfere effectively with HIV-1 cell entry. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.02.004
• 作为产物：
  描述：

  乙基-4-异叠酸苯酯 在 sodium hydroxide 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 5.0h， 生成 4-[[3-[4-[(4-Fluorophenyl)methyl]-1-piperidyl]propyl-phenyl-carbamoyl]amino]benzoic acid
  参考文献：
  名称：

  CCR5 antagonists as anti-HIV-1 agents. Part 2: Synthesis and biological evaluation of N-[3-(4-benzylpiperidin-1-yl)propyl]-N,N′-diphenylureas

  摘要：

  We have previously reported the novel lead compound 1a as a CCR5 antagonist for treatment of HIV-1 infection. SAR studies on incorporating various acyl groups as a replacement for the 5-oxopyrrolidine-3-carbonyl group of the lead structure resulted in the discovery of N-[3-(4-benzylpiperidin-1-yl)propyl]-N,N-1-diphenylurea (4a) with significantly improved CCR5 binding affinity. Substitutions (4-Cl, 4e,f; 4-Me, 4i) on the N'-phenyl ring further increased the binding affinity. Introduction of polar substituents on the phenyl ring of the 4-benzylpiperidine moiety enhanced the inhibitory activity of the HIV-1 envelope-mediated membrane fusion (4v,w), suggesting that polar substituents at this position can interfere effectively with HIV-1 cell entry. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.02.004

文献信息

• CCR5 antagonists as anti-HIV-1 agents. Part 2: Synthesis and biological evaluation of N-[3-(4-benzylpiperidin-1-yl)propyl]-N,N′-diphenylureas
  作者：Shinichi Imamura、Osamu Kurasawa、Yoshi Nara、Takashi Ichikawa、Youichi Nishikawa、Takehiro Iida、Shohei Hashiguchi、Naoyuki Kanzaki、Yuji Iizawa、Masanori Baba、Yoshihiro Sugihara

  DOI：10.1016/j.bmc.2004.02.004

  日期：2004.5

  We have previously reported the novel lead compound 1a as a CCR5 antagonist for treatment of HIV-1 infection. SAR studies on incorporating various acyl groups as a replacement for the 5-oxopyrrolidine-3-carbonyl group of the lead structure resulted in the discovery of N-[3-(4-benzylpiperidin-1-yl)propyl]-N,N-1-diphenylurea (4a) with significantly improved CCR5 binding affinity. Substitutions (4-Cl, 4e,f; 4-Me, 4i) on the N'-phenyl ring further increased the binding affinity. Introduction of polar substituents on the phenyl ring of the 4-benzylpiperidine moiety enhanced the inhibitory activity of the HIV-1 envelope-mediated membrane fusion (4v,w), suggesting that polar substituents at this position can interfere effectively with HIV-1 cell entry. (C) 2004 Elsevier Ltd. All rights reserved.