9-[4-[2-(1-methylethyl)-4-[[[4'-(trifluoromethyl)[1,1'-biphenyl]-2-yl]carbonyl]amino]-1H-benzimidazol-1-yl]butyl]-N-(2,2,2-trifluoroethyl)-9H-fluorene-9-carboxamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: 9-[4-[2-(1-methylethyl)-4-[[[4'-(trifluoromethyl)[1,1'-biphenyl]-2-yl]carbonyl]amino]-1H-benzimidazol-1-yl]butyl]-N-(2,2,2-trifluoroethyl)-9H-fluorene-9-carboxamide
• 英文别名: 9-(4-{2-Isopropyl-4-[(4''-trifluoromethyl-biphenyl-2-carbonyl)-amino]-benzoimidazol-1-yl}-butyl)-9H-fluorene-9-carboxylic acid (2,2,2-trifluoro-ethyl)-amide；9-[4-[2-propan-2-yl-4-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]benzimidazol-1-yl]butyl]-N-(2,2,2-trifluoroethyl)fluorene-9-carboxamide
• 化学式: C₄₄H₃₈F₆N₄O₂
• 分子量: 768.802
• InChiKey: OCKWNBAFSLXMEG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  10.2
• 重原子数：
  56
• 可旋转键数：
  11
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  76
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  4-三氟甲基-联苯-2-甲酸 在 草酰氯 、 三乙胺 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.5h， 生成 9-[4-[2-(1-methylethyl)-4-[[[4'-(trifluoromethyl)[1,1'-biphenyl]-2-yl]carbonyl]amino]-1H-benzimidazol-1-yl]butyl]-N-(2,2,2-trifluoroethyl)-9H-fluorene-9-carboxamide
  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
• US6472414B1
  申请人：——

  公开号：US6472414B1

  公开（公告）日：2002-10-29
• 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.