neopentyl 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carbonylcarbamate | 1072113-20-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: neopentyl 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carbonylcarbamate
• 英文别名: 2,2-dimethylpropyl N-[5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methylpyrazole-3-carbonyl]carbamate
• CAS: 1072113-20-2
• 化学式: C₂₃H₂₂Cl₃N₃O₃
• 分子量: 494.805
• InChiKey: OUMDKQMLKUHZBZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.3
• 重原子数：
  32
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  73.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  5-(4-氯苯基)-1-(2,4-二氯苯基)-4-甲基-1H-吡唑-3-羧酰胺 、 氯仿酸新戊酯 在 sodium hexamethyldisilazane 作用下， 以 四氢呋喃 为溶剂， 反应 16.83h， 生成 neopentyl 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carbonylcarbamate
  参考文献：
  名称：

  Synthesis and structure–activity relationship of novel diarylpyrazole imide analogues as CB1 cannabinoid receptor ligands

  摘要：

  A myriad of research groups have been engaged in searching for novel CB1 receptor antagonists, since SR141716A (rimonabant), a CB1 receptor antagonist, was discovered for an obesity treatment. In this research, extended series, based on the 1,5-diarylpyrazole template of rimonabant, was synthesized and tested for CB1 receptor binding affinity. In the present study, N-piperidinylcarboxamide group of rimonabant was replaced with the corresponding sulfonamide, imide, N-methylimide and methylenediamide, respectively. The SAR studies to optimize the CB1 binding affinity led to the potent imide derivatives. The in vivo efficacy test of a derivative (16f) gave a promising result for this novel scaffold. In order to explore physicochemical properties (hydrophobic, steric and electronic) of the representative imide derivatives responsible for their CB1 receptor binding affinity, quantitative structure activity relationship (QSAR) studies were performed. Hansch QSAR models, which were moderate in the explanation for SAR, were generated with hydrophobic, steric and electronic properties of substituents. Especially, the Taft Es-based parabolic model was obtained with the best correlation result (r(2) = 0.846). (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.03.006

文献信息

• Azole Derivatives as Cannabinoid CB1 Receptor Antagonists
  申请人：LEE Jinhwa

  公开号：US20080262066A1

  公开（公告）日：2008-10-23

  A novel azole compound of formula (I) or a pharmaceutically acceptable salt thereof is effective as a cannabinoid CB 1 receptor inverse agonist or antagonist, which is useful for preventing or treating obesity and obesity-related metabolic disorders. The prevention also provides a method for preparing same, a pharmaceutical composition containing same, and a method for preventing or treating obesity and obesity-related metabolic disorders.

  化合物(I)的新颖唑类化合物或其药用盐作为大麻素CB1受体的反向激动剂或拮抗剂具有良好效果，可用于预防或治疗肥胖和与肥胖相关的代谢紊乱。预防还提供了一种制备该化合物的方法，含有该化合物的药物组合物，以及预防或治疗肥胖和与肥胖相关的代谢紊乱的方法。
• Synthesis and structure–activity relationship of novel diarylpyrazole imide analogues as CB1 cannabinoid receptor ligands
  作者：Kwang-Seop Song、Min Ju Kim、Hee Jeong Seo、Sung-Han Lee、Myung Eun Jung、Soo-Un Kim、Jeongmin Kim、Jinhwa Lee

  DOI：10.1016/j.bmc.2009.03.006

  日期：2009.4

  A myriad of research groups have been engaged in searching for novel CB1 receptor antagonists, since SR141716A (rimonabant), a CB1 receptor antagonist, was discovered for an obesity treatment. In this research, extended series, based on the 1,5-diarylpyrazole template of rimonabant, was synthesized and tested for CB1 receptor binding affinity. In the present study, N-piperidinylcarboxamide group of rimonabant was replaced with the corresponding sulfonamide, imide, N-methylimide and methylenediamide, respectively. The SAR studies to optimize the CB1 binding affinity led to the potent imide derivatives. The in vivo efficacy test of a derivative (16f) gave a promising result for this novel scaffold. In order to explore physicochemical properties (hydrophobic, steric and electronic) of the representative imide derivatives responsible for their CB1 receptor binding affinity, quantitative structure activity relationship (QSAR) studies were performed. Hansch QSAR models, which were moderate in the explanation for SAR, were generated with hydrophobic, steric and electronic properties of substituents. Especially, the Taft Es-based parabolic model was obtained with the best correlation result (r(2) = 0.846). (C) 2009 Elsevier Ltd. All rights reserved.