2-[2-(4-chloro-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-2-cyclohexyl-N-[2-fluoro-4-(1H-tetrazol-5-yl)-phenyl]-acetamide | 1162677-43-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: 2-[2-(4-chloro-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-2-cyclohexyl-N-[2-fluoro-4-(1H-tetrazol-5-yl)-phenyl]-acetamide
• 英文别名: 2-[2-(4-chlorophenyl)-5,6-difluorobenzimidazol-1-yl]-2-cyclohexyl-N-[2-fluoro-4-(2H-tetrazol-5-yl)phenyl]acetamide
• CAS: 1162677-43-1；1162677-42-0；1162677-40-8
• 化学式: C₂₈H₂₃ClF₃N₇O
• 分子量: 565.985
• InChiKey: BFWQNCCFSCRIGZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.7
• 重原子数：
  40
• 可旋转键数：
  6
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  101
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  环己基乙酸 在 4-二甲氨基吡啶 、 氯化亚砜 、 sodium azide 、 溴 、 三乙胺盐酸盐 、 caesium carbonate 、 lithium hydroxide 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 邻二甲苯 、 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 2-[2-(4-chloro-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-2-cyclohexyl-N-[2-fluoro-4-(1H-tetrazol-5-yl)-phenyl]-acetamide
  参考文献：
  名称：

  Optimization of a novel class of benzimidazole-based farnesoid X receptor (FXR) agonists to improve physicochemical and ADME properties

  摘要：

  Structure-guided lead optimization of recently described benzimidazolyl acetamides addressed the key liabilities of the previous lead compound 1. These efforts culminated in the discovery of 4-{(S)-2-[2-(4-chloro-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-2-cyclohexyl-acetylamino}-3-fluoro-benzoic acid 7g, a highly potent and selective FXR agonist with excellent physicochemical and ADME properties and potent lipid lowering activity after oral administration to LDL receptor deficient mice. (c) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.12.123

文献信息

• CARBOXYL- OR HYDROXYL-SUBSTITUTED BENZIMIDAZOLE DERIVATIVES
  申请人：Benson Gregory Martin

  公开号：US20090163552A1

  公开（公告）日：2009-06-25

  This invention relates to novel carboxyl- or hydroxyl-substituted benzimidazole derivatives of formula (I) wherein R 1 to R 6 are as defined in the description and in the claims, as well as physiologically acceptable salts and esters thereof. These compounds bind to FXR and can be used as medicaments.

  这项发明涉及公式（I）中的新型羧基或羟基取代苯并咪唑衍生物， 其中R1至R6如描述和索赔中所定义，以及其生理上可接受的盐和酯。这些化合物与FXR结合，可用作药物。
• US7816540B2
  申请人：——

  公开号：US7816540B2

  公开（公告）日：2010-10-19
• [EN] CARBOXYL- OR HYDROXYLSUBSTITUTED BENZIMIDAZOLE DERIVATIVES<br/>[FR] DÉRIVÉS DE BENZIMIDAZOLE SUBSTITUÉS PAR CARBOXYLE OU HYDROXYLE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2009080555A2

  公开（公告）日：2009-07-02

  This invention relates to novel carboxyl- or hydroxylsubstituted benzimidazole derivatives of formula (I) wherein R1 to R6 are as defined in the description and in the claims, as well as physiologically acceptable salts and esters thereof. These compounds bind to FXR and can be used as medicaments.
• Optimization of a novel class of benzimidazole-based farnesoid X receptor (FXR) agonists to improve physicochemical and ADME properties
  作者：Hans G.F. Richter、G.M. Benson、K.H. Bleicher、D. Blum、E. Chaput、N. Clemann、S. Feng、C. Gardes、U. Grether、P. Hartman、B. Kuhn、R.E. Martin、J.-M. Plancher、M.G. Rudolph、F. Schuler、S. Taylor

  DOI：10.1016/j.bmcl.2010.12.123

  日期：2011.2

  Structure-guided lead optimization of recently described benzimidazolyl acetamides addressed the key liabilities of the previous lead compound 1. These efforts culminated in the discovery of 4-(S)-2-[2-(4-chloro-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-2-cyclohexyl-acetylamino}-3-fluoro-benzoic acid 7g, a highly potent and selective FXR agonist with excellent physicochemical and ADME properties and potent lipid lowering activity after oral administration to LDL receptor deficient mice. (c) 2011 Elsevier Ltd. All rights reserved.