(E)-3-(3,4-dichlorophenyl)-N-{5-[4-(5-methoxy-1H-indol-3-yl)-piperidin-1-yl]pentyl}acrylamide | 299173-58-3

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: (E)-3-(3,4-dichlorophenyl)-N-{5-[4-(5-methoxy-1H-indol-3-yl)-piperidin-1-yl]pentyl}acrylamide
• 英文别名: (E)-3-(3,4-Dichloro-phenyl)-N-{5-[4-(5-methoxy-1H-indol-3-yl)-piperidin-1-yl]-pentyl}-acrylamide；(E)-3-(3,4-dichlorophenyl)-N-[5-[4-(5-methoxy-1H-indol-3-yl)piperidin-1-yl]pentyl]prop-2-enamide
• CAS: 299173-58-3
• 化学式: C₂₈H₃₃Cl₂N₃O₂
• 分子量: 514.495
• InChiKey: WQFOIENCGNAPLN-UXBLZVDNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.3
• 重原子数：
  35
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  57.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (E)-3-(3,4-dichlorophenyl)-N-{5-[4-(5-methoxy-1H-indol-3-yl)-piperidin-1-yl]pentyl}acrylamide 在 吡啶盐酸盐 作用下， 反应 48.0h， 以40%的产率得到SB 282241
  参考文献：
  名称：

  CCR2:  Characterization of the Antagonist Binding Site from a Combined Receptor Modeling/Mutagenesis Approach

  摘要：

  We describe here a classical molecular modeling exercise that was carried out to provide a basis for the design of novel antagonist ligands of the CCR2 receptor. Using a theoretical model of the CCR2 receptor, docking studies were carried out to define plausible binding modes for the various known antagonist ligands, including our own series of indole piperidine compounds. On the basis of these results, a number of site-directed mutations (SDM) were designed that were intended to verify the proposed docking models. From these it was clear that further refinements would be necessary in the model. This was aided by the publication of a crystal structure of bovine enabled us to define ligand-docking hypotheses that were in complete agreement with the results of the SDM experiments.

  DOI：

  10.1021/jm030862l
• 作为产物：
  描述：

  5-氨基-1-戊醇 在 四溴化碳 、 碳酸氢钠 、 N,N-二异丙基乙胺 、 三苯基膦 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 10.33h， 生成 (E)-3-(3,4-dichlorophenyl)-N-{5-[4-(5-methoxy-1H-indol-3-yl)-piperidin-1-yl]pentyl}acrylamide
  参考文献：
  名称：

  CCR2:  Characterization of the Antagonist Binding Site from a Combined Receptor Modeling/Mutagenesis Approach

  摘要：

  We describe here a classical molecular modeling exercise that was carried out to provide a basis for the design of novel antagonist ligands of the CCR2 receptor. Using a theoretical model of the CCR2 receptor, docking studies were carried out to define plausible binding modes for the various known antagonist ligands, including our own series of indole piperidine compounds. On the basis of these results, a number of site-directed mutations (SDM) were designed that were intended to verify the proposed docking models. From these it was clear that further refinements would be necessary in the model. This was aided by the publication of a crystal structure of bovine enabled us to define ligand-docking hypotheses that were in complete agreement with the results of the SDM experiments.

  DOI：

  10.1021/jm030862l

文献信息

• CCR2B receptor antagonists: conversion of a weak HTS hit to a potent lead compound
  作者：Ian T Forbes、David G Cooper、Emma K Dodds、Deirdre M.B Hickey、Robert J Ife、Malcolm Meeson、Martin Stockley、Theo A Berkhout、Jayneeta Gohil、Pieter H.E Groot、Kitty Moores

  DOI：10.1016/s0960-894x(00)00347-4

  日期：2000.8

  A weak HTS hit at the CCR2B receptor has been converted into a potent antagonist by array SAR studies. Selectivity over the closely related CCR5 receptor is also achieved. (C) 2000 Elsevier Science Ltd. All rights reserved.
• CCR2:  Characterization of the Antagonist Binding Site from a Combined Receptor Modeling/Mutagenesis Approach
  作者：Theo A. Berkhout、Frank E. Blaney、Angela M. Bridges、David G. Cooper、Ian T. Forbes、Andrew D. Gribble、Pieter H. E. Groot、Adam Hardy、Robert J. Ife、Rejbinder Kaur、Kitty E. Moores、Helen Shillito、Jennifer Willetts、Jason Witherington

  DOI：10.1021/jm030862l

  日期：2003.9.1

  We describe here a classical molecular modeling exercise that was carried out to provide a basis for the design of novel antagonist ligands of the CCR2 receptor. Using a theoretical model of the CCR2 receptor, docking studies were carried out to define plausible binding modes for the various known antagonist ligands, including our own series of indole piperidine compounds. On the basis of these results, a number of site-directed mutations (SDM) were designed that were intended to verify the proposed docking models. From these it was clear that further refinements would be necessary in the model. This was aided by the publication of a crystal structure of bovine enabled us to define ligand-docking hypotheses that were in complete agreement with the results of the SDM experiments.