1-(4-chlorophenyl)-2-(2,4-dichlorophenyl)-N-[(1R,2R)-2-hydroxycyclohexyl]-1H-imidazole-4-carboxamide | 527376-33-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 1-(4-chlorophenyl)-2-(2,4-dichlorophenyl)-N-[(1R,2R)-2-hydroxycyclohexyl]-1H-imidazole-4-carboxamide
• 英文别名: 1-(4-chlorophenyl)-2-(2,4-dichlorophenyl)-N-[(1R,2R)-2-hydroxycyclohexyl]imidazole-4-carboxamide
• CAS: 527376-33-6
• 化学式: C₂₂H₂₀Cl₃N₃O₂
• 分子量: 464.779
• InChiKey: IMULKGNJBJYZHH-UYAOXDASSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  67.2
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  N-[(1R,2R)-2-(benzyloxy)cyclohexyl]-1-(4-chlorophenyl)-2-(2,4-dichlorophenyl)-1H-imidazole-4-carboxamide 在 碘代三甲硅烷 作用下， 以 二氯甲烷 为溶剂， 以67%的产率得到1-(4-chlorophenyl)-2-(2,4-dichlorophenyl)-N-[(1R,2R)-2-hydroxycyclohexyl]-1H-imidazole-4-carboxamide
  参考文献：
  名称：

  [EN] PREPARATION OF IMIDAZOLE DERIVATIVES AND METHODS OF USE
  [FR] PREPARATION DE DERIVES IMIDAZOLES ET LEURS PROCEDES D'UTILISATION

  摘要：

  公开号：

  WO2005099705A3

文献信息

• Preparation and use of imidazole derivatives for treatment of obesity
  申请人：Smith A. Roger

  公开号：US20050256167A1

  公开（公告）日：2005-11-17

  This invention relates to substituted imidazole derivatives which have been found to suppress appetite and induce weight loss. The invention also provides methods for synthesis of the compounds, pharmaceutical compositions comprising the compounds, and methods of using such compositions for inducing weight loss and treating obesity and obesity-related disorders.

  本发明涉及取代咪唑衍生物，发现其能够抑制食欲并引起减重。本发明还提供了合成该化合物的方法，包括该化合物的药物组合物，以及使用这样的组合物诱导减重和治疗肥胖和肥胖相关疾病的方法。
• Optimization of imidazole amide derivatives as cannabinoid-1 receptor antagonists for the treatment of obesity
  作者：Roger A. Smith、Zahra Fathi、Furahi Achebe、Christiana Akuche、Su-Ellen Brown、Soongyu Choi、Jianmei Fan、Susan Jenkins、Harold C.E. Kluender、Anish Konkar、Rico Lavoie、Ronald Mays、Jennifer Natoli、Stephen J. O’Connor、Astrid A. Ortiz、Ning Su、Christy Taing、Susan Tomlinson、Theresa Tritto、Gan Wang、Stephan-Nicholas Wirtz、Wai Wong、Xiao-Fan Yang、Shihong Ying、Zhonghua Zhang

  DOI：10.1016/j.bmcl.2007.03.011

  日期：2007.5

  Several imidazole-based cyclohexyl amides were identified as potent CB-1 antagonists, but they exhibited poor oral exposure in rodents. Incorporation of a hydroxyl moiety on the cyclohexyl ring provided a dramatic improvement in oral exposure, together with a ca. 10-fold decrease in potency. Further optimization provided the imidazole 2-hydroxy-cyclohexyl amide 45, which exhibited hCB-1 K-i = 3.7 nM and caused significant appetite suppression and robust, dose-dependent reduction of body weight gain in industry-standard rat models. (c) 2007 Elsevier Ltd. All rights reserved.
• US6960601B2
  申请人：——

  公开号：US6960601B2

  公开（公告）日：2005-11-01