N'-(4-chlorophenyl)-N-(3-{4-[4-(morpholin-4-ylsulfonyl)benzyl]piperidin-1-yl}propyl)-N-phenylurea hydrochloride

• 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: N'-(4-chlorophenyl)-N-(3-{4-[4-(morpholin-4-ylsulfonyl)benzyl]piperidin-1-yl}propyl)-N-phenylurea hydrochloride
• 英文别名: N'-(4-Chlorophenyl)-N-(3-{4-[4-(4-morpholinylsulfonyl)benzyl]-1-piperidinyl}propyl)-N-phenylurea hydrochloride；3-(4-Chlorophenyl)-1-[3-[4-[(4-morpholin-4-ylsulfonylphenyl)methyl]piperidin-1-yl]propyl]-1-phenylurea;hydrochloride
• 化学式: C₃₂H₃₉ClN₄O₄S*ClH
• 分子量: 647.666
• InChiKey: HVRFAWJVAYAWMK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.17
• 重原子数：
  43
• 可旋转键数：
  10
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  90.6
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  N-苯基甲酰胺 在 盐酸 、 potassium carbonate 、 caesium carbonate 、 三乙胺 、 potassium iodide 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 异丙醇 、 丙酮 、 乙腈 为溶剂， 反应 19.0h， 生成 N'-(4-chlorophenyl)-N-(3-{4-[4-(morpholin-4-ylsulfonyl)benzyl]piperidin-1-yl}propyl)-N-phenylurea hydrochloride
  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

• UREA COMPOUNDS, PROCESS FOR PRODUCING THE SAME AND USE THEREOF
  申请人：Takeda Pharmaceutical Company Limited

  公开号：EP1219605B1

  公开（公告）日：2006-05-10
• US6787650B1
  申请人：——

  公开号：US6787650B1

  公开（公告）日：2004-09-07
• 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.