N-(adamantan-1-yl)-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)-1H-pyrrole-3-carboxamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: N-(adamantan-1-yl)-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)-1H-pyrrole-3-carboxamide
• 英文别名: N-(1-adamantyl)-5-(4-chloro-3-methylphenyl)-1-[(4-methylphenyl)methyl]pyrrole-3-carboxamide
• 化学式: C₃₀H₃₃ClN₂O
• 分子量: 473.058
• InChiKey: HPVKFMJMYJDNHE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.2
• 重原子数：
  34
• 可旋转键数：
  5
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  34
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为产物：
  描述：

  4-氯-3-甲基苯乙酮 在 三乙烯二胺 、 氯化亚砜 、 盐酸羟胺 、 水 、 sodium acetate 、 sodium hydride 、 sodium hydroxide 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 、 甲苯 、 mineral oil 为溶剂， 反应 19.42h， 生成 N-(adamantan-1-yl)-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)-1H-pyrrole-3-carboxamide
  参考文献：
  名称：

  Synthesis, pharmacological evaluation and docking studies of pyrrole structure-based CB 2 receptor antagonists

  摘要：

  During the last years, there has been a continuous interest in the development of cannabinoid receptor ligands that may serve as therapeutic agents and/or as experimental tools. This prompted us to design and synthesize analogues of the CB2 receptor antagonist N-fenchyl-5-(4-chloro-3-methyl-phenyl)-1-(4-methyl-benzyl)-1H-pyrazole-3-carboxamide (SR144528). The structural modifications involved the bioisosteric replacement of the pyrazole ring by a pyrrole ring and variations on the amine carbamoyl substituents. Two of these compounds, the fenchyl pyrrole analogue 6 and the myrtanyl derivative 10, showed high affinity (K-i in the low nM range) and selectivity for the CB2 receptor and both resulted to be antagonists/inverse agonists in [S-35]-GTP gamma S binding analysis and in an in vitro CB2 receptor bioassay. Cannabinoid receptor binding data of the series allowed identifying steric constraints within the CB2 binding pocket using a study of Van der Waals' volume maps. Glide docking studies revealed that all docked compounds bind in the same region of the CB2 receptor inactive state model. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.06.057

文献信息

• Synthesis, pharmacological evaluation and docking studies of pyrrole structure-based CB 2 receptor antagonists
  作者：Giulio Ragusa、María Gómez-Cañas、Paula Morales、Dow P. Hurst、Francesco Deligia、Ruth Pazos、Gerard A. Pinna、Javier Fernández-Ruiz、Pilar Goya、Patricia H. Reggio、Nadine Jagerovic、Moisés García-Arencibia、Gabriele Murineddu

  DOI：10.1016/j.ejmech.2015.06.057

  日期：2015.8

  During the last years, there has been a continuous interest in the development of cannabinoid receptor ligands that may serve as therapeutic agents and/or as experimental tools. This prompted us to design and synthesize analogues of the CB2 receptor antagonist N-fenchyl-5-(4-chloro-3-methyl-phenyl)-1-(4-methyl-benzyl)-1H-pyrazole-3-carboxamide (SR144528). The structural modifications involved the bioisosteric replacement of the pyrazole ring by a pyrrole ring and variations on the amine carbamoyl substituents. Two of these compounds, the fenchyl pyrrole analogue 6 and the myrtanyl derivative 10, showed high affinity (K-i in the low nM range) and selectivity for the CB2 receptor and both resulted to be antagonists/inverse agonists in [S-35]-GTP gamma S binding analysis and in an in vitro CB2 receptor bioassay. Cannabinoid receptor binding data of the series allowed identifying steric constraints within the CB2 binding pocket using a study of Van der Waals' volume maps. Glide docking studies revealed that all docked compounds bind in the same region of the CB2 receptor inactive state model. (C) 2015 Elsevier Masson SAS. All rights reserved.