(E)-3-(1-(2-morpholinoethyl)-1H-indol-3-yl)-2-(phenylsulfonyl)prop-2-enenitrile | 1334479-26-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: (E)-3-(1-(2-morpholinoethyl)-1H-indol-3-yl)-2-(phenylsulfonyl)prop-2-enenitrile
• 英文别名: (E)-2-(benzenesulfonyl)-3-[1-(2-morpholin-4-ylethyl)indol-3-yl]prop-2-enenitrile
• CAS: 1334479-26-3
• 化学式: C₂₃H₂₃N₃O₃S
• 分子量: 421.52
• InChiKey: SRTMLRVZSLOOCF-LTGZKZEYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  83.7
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-(2-氯乙基)吗啉 、 (2E)-3-(1H-indol-3-yl)-2-(phenylsulfonyl)acrylonitrile 在 potassium hydroxide 作用下， 以 二氯甲烷 、 水 为溶剂， 以40%的产率得到(E)-3-(1-(2-morpholinoethyl)-1H-indol-3-yl)-2-(phenylsulfonyl)prop-2-enenitrile
  参考文献：
  名称：

  Homology modeling in tandem with 3D-QSAR analyses: A computational approach to depict the agonist binding site of the human CB2 receptor

  摘要：

  CB2 receptor belongs to the large family of G-protein coupled receptors (GPCRs) controlling a wide variety of signal transduction. The recent crystallographic determination of human beta 2 adrenoreceptor and its high sequence similarity with human CB2 receptor (hCB2) prompted us to compute a theoretical model of hCB2 based also on beta 2 adrenoreceptor coordinates. This model has been employed to perform docking and molecular dynamic simulations on WIN-55,212-2 (CB2 agonist commonly used in binding experiments), in order to identify the putative CB2 receptor agonist binding site, followed by molecular docking studies on a series of indol-3-yl-tetramethylcyclopropyl ketone derivatives, a novel class of potent CB2 agonists. Successively, docking-based Comparative Molecular Fields Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA) studies were also performed. The CoMSIA model resulted to be the more predictive, showing r(ncv)(2) = 0.96, r(cv)(2) = 0.713, SEE = 0.193, F = 125.223, and r(pred)(2) = 0.78. The obtained 3D-QSAR models allowed us to derive more complete guidelines for the design of new analogues with improved potency so as to synthesize new indoles showing high CB2 affinity. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.07.023

文献信息

• Homology modeling in tandem with 3D-QSAR analyses: A computational approach to depict the agonist binding site of the human CB2 receptor
  作者：Elena Cichero、Alessia Ligresti、Marco Allarà、Vincenzo di Marzo、Zelda Lazzati、Pasqualina D’Ursi、Anna Marabotti、Luciano Milanesi、Andrea Spallarossa、Angelo Ranise、Paola Fossa

  DOI：10.1016/j.ejmech.2011.07.023

  日期：2011.9

  CB2 receptor belongs to the large family of G-protein coupled receptors (GPCRs) controlling a wide variety of signal transduction. The recent crystallographic determination of human beta 2 adrenoreceptor and its high sequence similarity with human CB2 receptor (hCB2) prompted us to compute a theoretical model of hCB2 based also on beta 2 adrenoreceptor coordinates. This model has been employed to perform docking and molecular dynamic simulations on WIN-55,212-2 (CB2 agonist commonly used in binding experiments), in order to identify the putative CB2 receptor agonist binding site, followed by molecular docking studies on a series of indol-3-yl-tetramethylcyclopropyl ketone derivatives, a novel class of potent CB2 agonists. Successively, docking-based Comparative Molecular Fields Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA) studies were also performed. The CoMSIA model resulted to be the more predictive, showing r(ncv)(2) = 0.96, r(cv)(2) = 0.713, SEE = 0.193, F = 125.223, and r(pred)(2) = 0.78. The obtained 3D-QSAR models allowed us to derive more complete guidelines for the design of new analogues with improved potency so as to synthesize new indoles showing high CB2 affinity. (C) 2011 Elsevier Masson SAS. All rights reserved.