9-[4-(5-Methyl-4-nitro-benzoimidazol-1-yl)-butyl]-9H-fluorene-9-carboxylic acid (2,2,2-trifluoro-ethyl)-amide | 194220-00-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: 9-[4-(5-Methyl-4-nitro-benzoimidazol-1-yl)-butyl]-9H-fluorene-9-carboxylic acid (2,2,2-trifluoro-ethyl)-amide
• 英文别名: 9-[4-(5-methyl-4-nitrobenzimidazol-1-yl)butyl]-N-(2,2,2-trifluoroethyl)fluorene-9-carboxamide
• CAS: 194220-00-3
• 化学式: C₂₈H₂₅F₃N₄O₃
• 分子量: 522.527
• InChiKey: LAIWPUMESBSTGZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  38
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  92.7
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  9-[4-(5-Methyl-4-nitro-benzoimidazol-1-yl)-butyl]-9H-fluorene-9-carboxylic acid (2,2,2-trifluoro-ethyl)-amide 在 palladium 10% on activated carbon 氢气 作用下， 以 乙醇 为溶剂， 反应 14.0h， 以97%的产率得到9-[4-(4-Amino-5-methyl-benzoimidazol-1-yl)-butyl]-9H-fluorene-9-carboxylic acid (2,2,2-trifluoro-ethyl)-amide
  参考文献：
  名称：

  CONFORMATIONALLY RESTRICTED AROMATIC INHIBITORS OF MICROSOMAL TRIGLYCERIDE TRANSFER PROTEIN AND METHOD

  摘要：

  公开号：

  EP0904262B1
• 作为产物：
  描述：

  9-芴甲酸 在 正丁基锂 、 草酰氯 、 potassium carbonate 、 三乙胺 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 120.16h， 生成 9-[4-(5-Methyl-4-nitro-benzoimidazol-1-yl)-butyl]-9H-fluorene-9-carboxylic acid (2,2,2-trifluoro-ethyl)-amide
  参考文献：
  名称：

  A Novel Series of Highly Potent Benzimidazole-Based Microsomal Triglyceride Transfer Protein Inhibitors

  摘要：

  A series of benzimidazole-based analogues of the potent MTP inhibitor EMS-201038 were discovered. Incorporation of an unsubstituted benzimidazole moiety in place of a piperidine group afforded potent inhibitors of MTP in vitro which were weakly active in vivo. Appropriate substitution on the benzimidazole ring, especially with small alkyl groups, led to dramatic increases in potency, both in a cellular assay of apoB secretion and especially in animal models of cholesterol lowering. The most potent in this series, 3g (BMS-212122), was significantly more potent than EMS-201038 in reducing plasma lipids (cholesterol, VLDL/LDL, TG) in both hamsters and cynomolgus monkeys.

  DOI：

  10.1021/jm000494a

文献信息

• CONFORMATIONALLY RESTRICTED AROMATIC INHIBITORS OF MICROSOMAL TRIGLYCERIDE TRANSFER PROTEIN AND METHOD
  申请人：BRISTOL-MYERS SQUIBB COMPANY

  公开号：EP0904262B1

  公开（公告）日：2004-04-21
• A Novel Series of Highly Potent Benzimidazole-Based Microsomal Triglyceride Transfer Protein Inhibitors
  作者：Jeffrey A. Robl、Richard Sulsky、Chong-Qing Sun、Ligaya M. Simpkins、Tammy Wang、John K. Dickson、Ying Chen、David R. Magnin、Prakash Taunk、William A. Slusarchyk、Scott A. Biller、Shih-Jung Lan、Fergal Connolly、Lori K. Kunselman、Talal Sabrah、Haris Jamil、David Gordon、Thomas W. Harrity、John R. Wetterau

  DOI：10.1021/jm000494a

  日期：2001.3.1

  A series of benzimidazole-based analogues of the potent MTP inhibitor EMS-201038 were discovered. Incorporation of an unsubstituted benzimidazole moiety in place of a piperidine group afforded potent inhibitors of MTP in vitro which were weakly active in vivo. Appropriate substitution on the benzimidazole ring, especially with small alkyl groups, led to dramatic increases in potency, both in a cellular assay of apoB secretion and especially in animal models of cholesterol lowering. The most potent in this series, 3g (BMS-212122), was significantly more potent than EMS-201038 in reducing plasma lipids (cholesterol, VLDL/LDL, TG) in both hamsters and cynomolgus monkeys.