2-(4-bromo-phenyl)-5-trifluoromethyl-1H-benzoimidazole | 1370534-53-4

• 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-(4-bromo-phenyl)-5-trifluoromethyl-1H-benzoimidazole
• 英文别名: 2-(4-bromophenyl)-6-(trifluoromethyl)-1H-benzimidazole
• CAS: 1370534-53-4
• 化学式: C₁₄H₈BrF₃N₂
• 分子量: 341.13
• InChiKey: OEGWMOXTQVGTBQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  28.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(4-bromo-phenyl)-5-trifluoromethyl-1H-benzoimidazole 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 碳酸氢钠 作用下， 以 四氢呋喃 、 N-甲基吡咯烷酮 、 水 为溶剂， 反应 34.0h， 生成 3-[[5-[4-[6-(trifluoromethyl)-1H-benzimidazol-2-yl]phenyl]pyridin-2-yl]amino]propanoic acid
  参考文献：
  名称：

  [EN] COMPOUNDS AS DGAT-1 INHIBITORS
  [FR] COMPOSÉS EN TANT QU'INHIBITEURS DE DGAT-1

  摘要：

  公开号：

  WO2013130370A3
• 作为产物：
  描述：

  4-溴苯甲酸 、 3,4-二胺基苄氧基三氟化物 在 吡啶 、 亚磷酸三苯酯 作用下， 反应 0.5h， 生成 2-(4-bromo-phenyl)-5-trifluoromethyl-1H-benzoimidazole
  参考文献：
  名称：

  [EN] IMIDAZOLE DERIVATIVES
  [FR] DÉRIVÉS D'IMIDAZOLE

  摘要：

  本文描述了式I的化合物。式I的化合物作为DGAT1抑制剂，可用于预防、治疗或作为高脂血症、糖尿病和肥胖的治疗药物。

  公开号：

  WO2012096813A1

文献信息

• [EN] IMIDAZOLE DERIVATIVES<br/>[FR] DÉRIVÉS D'IMIDAZOLE
  申请人：MERCK SHARP & DOHME

  公开号：WO2012096813A1

  公开（公告）日：2012-07-19

  Described herein are compounds of formula I. The compounds of formula I act as DGAT1 inhibitors and can be useful in preventing, treating or acting as a remedial agent for hyperlipidemia, diabetes mellitus and obesity.

  本文描述了式I的化合物。式I的化合物作为DGAT1抑制剂，可用于预防、治疗或作为高脂血症、糖尿病和肥胖的治疗药物。
• Accelerating the discovery of DGAT1 inhibitors through the application of parallel medicinal chemistry (PMC)
  作者：Yang Yu、Zhicai Wu、Zhi-Cai Shi、Shuwen He、Zhong Lai、Timothy A. Cernak、Petr Vachal、Min Liu、Jian Liu、Qingmei Hong、Tianying Jian、Deodial Guiadeen、Arto Krikorian、Donald M. Sperbeck、Andreas Verras、Lisa M. Sonatore、Beth A. Murphy、Judyann Wiltsie、Christine C. Chung、Judith N. Gorski、Jinqi Liu、Jianying Xiao、Michael Wolff、Sharon X. Tong、Maria Madeira、Bindhu V. Karanam、Dong-Ming Shen、James M. Balkovec、Robert J. De Vita、Shirly Pinto、Ravi P. Nargund

  DOI：10.1016/j.bmcl.2019.03.039

  日期：2019.6

  The parallel medicinal chemistry (PMC) was effectively applied to accelerate the optimization of diacylglycerol O-acyltransferase I (DGAT-1) inhibitors. Through a highly collaborative and iterative library design, synthesis and testing, a benzimidazole lead was rapidly and systematically advanced to a highly potent, selective and bioavailable DGAT1 inhibitor with the potential for further development.
• Fragment-based lead discovery of a novel class of small molecule antagonists of neuropeptide B/W receptor subtype 1 (GPR7)
  作者：Remond Moningka、F. Anthony Romero、Nicholas B. Hastings、Zhiqiang Guo、Ming Wang、Jerry Di Salvo、Ying Li、Dorina Trusca、Qiaoling Deng、Vincent Tong、Jenna L. Terebetski、Richard G. Ball、Feroze Ujjainwalla

  DOI：10.1016/j.bmcl.2020.127510

  日期：2020.12

  Here, we report the discovery of a new class of NPBWR1 antagonists identified from a fragment-based screen. Compound 1 (cAMP IC₅₀ = 250 µM; LE = 0.29) emerged as an initial hit. Further optimization of 1 by SAR-by-catalogue and chemical modification produced 21a (cAMP IC₅₀ = 30 nM; LE = 0.39) with a 6700-fold increase in potency from fragment 1. Somewhat surprisingly, Schild analysis of compound 21a suggested that in vitro inhibition of NPW-mediated effects on upon cAMP accumulation were saturable, and that compound 21a dose-dependently increased [125I]-hNPW23 dissociation rate constants from NPBWR1 in kinetic binding studies. Collectively, these data are inconsistent with a classic surmountable, orthosteric mechanism of inhibition. The benzimidazole inhibitors reported herein may therefore represent a mechanistically differentiated class of compounds with which to form a better appreciation of the pharmacology and physiological roles of this central neuropeptide system.
• [EN] COMPOUNDS AS DGAT-1 INHIBITORS<br/>[FR] COMPOSÉS EN TANT QU'INHIBITEURS DE DGAT-1
  申请人：MERCK SHARP & DOHME

  公开号：WO2013130370A3

  公开（公告）日：2015-06-18