4-[(4-Bromo-phenyl)-(5-fluoro-6-trifluoromethyl-1H-benzoimidazol-2-yl)-methylene]-piperidine-1-carboxylic acid tert-butyl ester | 846049-68-1

• 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: 4-[(4-Bromo-phenyl)-(5-fluoro-6-trifluoromethyl-1H-benzoimidazol-2-yl)-methylene]-piperidine-1-carboxylic acid tert-butyl ester
• 英文别名: tert-butyl 4-[(4-bromophenyl)-[5-fluoro-6-(trifluoromethyl)-1H-benzimidazol-2-yl]methylidene]piperidine-1-carboxylate
• CAS: 846049-68-1
• 化学式: C₂₅H₂₄BrF₄N₃O₂
• 分子量: 554.382
• InChiKey: FKPQBEZKIFVLHR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.5
• 重原子数：
  35
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  58.2
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  4-[(4-Bromo-phenyl)-(5-fluoro-6-trifluoromethyl-1H-benzoimidazol-2-yl)-methylene]-piperidine-1-carboxylic acid tert-butyl ester 在 palladium bis[bis(diphenylphosphino)ferrocene] dichloride 、 potassium acetate 、 三乙酰氧基硼氢化钠 、 三氟乙酸 作用下， 以 二氯甲烷 、 二甲基亚砜 为溶剂， 生成 2-{(1-Cyclopropylmethyl-piperidin-4-ylidene)-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-methyl}-5-fluoro-6-trifluoromethyl-1H-benzoimidazole
  参考文献：
  名称：

  Design and synthesis of orally efficacious benzimidazoles as melanin-concentrating hormone receptor 1 antagonists

  摘要：

  Biaryl urea lead compound 1 was discovered earlier in our MCH antagonist program. Novel benzimidazole analogues with increased chemical stability, devoid of the potential carcinogenic liability associated with a biarylamine moiety, were synthesized and evaluated to be potent MCH R1 antagonists. Two compounds in this series have demonstrated in vivo efficacy in a rodent obesity model. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.04.062
• 作为产物：
  描述：

  对溴苯乙腈 在 sodium ethanolate 、 二异丁基氢化铝 、 sodium hydrogensulfite 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 生成 4-[(4-Bromo-phenyl)-(5-fluoro-6-trifluoromethyl-1H-benzoimidazol-2-yl)-methylene]-piperidine-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Design and synthesis of orally efficacious benzimidazoles as melanin-concentrating hormone receptor 1 antagonists

  摘要：

  Biaryl urea lead compound 1 was discovered earlier in our MCH antagonist program. Novel benzimidazole analogues with increased chemical stability, devoid of the potential carcinogenic liability associated with a biarylamine moiety, were synthesized and evaluated to be potent MCH R1 antagonists. Two compounds in this series have demonstrated in vivo efficacy in a rodent obesity model. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.04.062

文献信息

• 2-Substituted benzimidazole derivatives as selective melanin concentrating hormone receptor antagonists for the treatment of obesity and related disorders
  申请人：Wu Wen-Lian

  公开号：US20050049269A1

  公开（公告）日：2005-03-03

  The present invention discloses compounds of formula I wherein Ar, X, R 1 and R 11 are herein defined, said compounds being novel antagonists for melanin-concentrating hormone (MCH), as well as methods for preparing such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising such MCH antagonists as well as methods of using them to treat obesity, metabolic disorders, eating disorders such as hyperphagia, and diabetes.

  本发明揭示了具有以下结构的化合物（I）其中Ar、X、R1和R11如下定义，所述化合物是新型黑素浓缩激素（MCH）拮抗剂，以及制备此类化合物的方法。在另一实施方案中，本发明揭示了包含这种MCH拮抗剂的药物组合物，以及使用它们治疗肥胖、代谢紊乱、食欲紊乱（如过食症）和糖尿病的方法。
• US7214691B2
  申请人：——

  公开号：US7214691B2

  公开（公告）日：2007-05-08
• Design and synthesis of orally efficacious benzimidazoles as melanin-concentrating hormone receptor 1 antagonists
  作者：Wen-Lian Wu、Duane A. Burnett、Mary Ann Caplen、Martin S. Domalski、Chad Bennett、William J. Greenlee、Brian E. Hawes、Kim O’Neill、Blair Weig、Daniel Weston、Brian Spar、Timothy Kowalski

  DOI：10.1016/j.bmcl.2006.04.062

  日期：2006.7

  Biaryl urea lead compound 1 was discovered earlier in our MCH antagonist program. Novel benzimidazole analogues with increased chemical stability, devoid of the potential carcinogenic liability associated with a biarylamine moiety, were synthesized and evaluated to be potent MCH R1 antagonists. Two compounds in this series have demonstrated in vivo efficacy in a rodent obesity model. (c) 2006 Elsevier Ltd. All rights reserved.