4-[N-(2-(trifluoromethyl)benzyl)benzamide](1,1′-biphenyl)-3-carboxylic acid

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-[N-(2-(trifluoromethyl)benzyl)benzamide](1,1′-biphenyl)-3-carboxylic acid
• 英文别名: 3-[4-[[2-(Trifluoromethyl)phenyl]methylcarbamoyl]phenyl]benzoic acid；3-[4-[[2-(trifluoromethyl)phenyl]methylcarbamoyl]phenyl]benzoic acid
• 化学式: C₂₂H₁₆F₃NO₃
• 分子量: 399.369
• InChiKey: ANLLSNAYTAPKED-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  66.4
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2-(三氟甲基)苄胺 在 4-二甲氨基吡啶 、 palladium diacetate 、 potassium carbonate 、 1,2-二氯乙烷 作用下， 以 二氯甲烷 、 水 、 丙酮 为溶剂， 反应 26.0h， 生成 4-[N-(2-(trifluoromethyl)benzyl)benzamide](1,1′-biphenyl)-3-carboxylic acid
  参考文献：
  名称：

  N-Benzylbenzamides: A Novel Merged Scaffold for Orally Available Dual Soluble Epoxide Hydrolase/Peroxisome Proliferator-Activated Receptor γ Modulators

  摘要：

  Metabolic syndrome (MetS) is a multifactorial disease cluster that consists of dyslipidemia, cardiovascular disease, type 2 diabetes mellitus, and obesity. MetS patients are strongly exposed to polypharmacy; however, the number of pharmacological compounds required for MetS treatment can be reduced by the application of multitarget compounds. This study describes the design of dual-target ligands that target soluble epoxide hydrolase (sEH) and the peroxisome proliferator-activated receptor type gamma (PPAR gamma). Simultaneous modulation of sEH and PPAR gamma can improve diabetic conditions and hypertension at once. N-Benzylbenzamide derivatives were determined to fit a merged sEH/PPAR gamma pharmacophore, and structure-activity relationship studies were performed on both targets, resulting in a submicromolar (sEH IC50 = 0.3 mu M/PPAR gamma EC50 = 0.3 mu M) modulator 14c. In vitro and in vivo evaluations revealed good ADME properties qualifying 14c as a pharmacological tool compound for long-term animal models of MetS.

  DOI：

  10.1021/acs.jmedchem.5b01239

文献信息

• <i>N</i>-Benzylbenzamides: A Novel Merged Scaffold for Orally Available Dual Soluble Epoxide Hydrolase/Peroxisome Proliferator-Activated Receptor γ Modulators
  作者：René Blöcher、Christina Lamers、Sandra K. Wittmann、Daniel Merk、Markus Hartmann、Lilia Weizel、Olaf Diehl、Astrid Brüggerhoff、Marcel Boß、Astrid Kaiser、Tim Schader、Tamara Göbel、Manuel Grundmann、Carlo Angioni、Jan Heering、Gerd Geisslinger、Mario Wurglics、Evi Kostenis、Bernhard Brüne、Dieter Steinhilber、Manfred Schubert-Zsilavecz、Astrid S. Kahnt、Ewgenij Proschak

  DOI：10.1021/acs.jmedchem.5b01239

  日期：2016.1.14

  Metabolic syndrome (MetS) is a multifactorial disease cluster that consists of dyslipidemia, cardiovascular disease, type 2 diabetes mellitus, and obesity. MetS patients are strongly exposed to polypharmacy; however, the number of pharmacological compounds required for MetS treatment can be reduced by the application of multitarget compounds. This study describes the design of dual-target ligands that target soluble epoxide hydrolase (sEH) and the peroxisome proliferator-activated receptor type gamma (PPAR gamma). Simultaneous modulation of sEH and PPAR gamma can improve diabetic conditions and hypertension at once. N-Benzylbenzamide derivatives were determined to fit a merged sEH/PPAR gamma pharmacophore, and structure-activity relationship studies were performed on both targets, resulting in a submicromolar (sEH IC50 = 0.3 mu M/PPAR gamma EC50 = 0.3 mu M) modulator 14c. In vitro and in vivo evaluations revealed good ADME properties qualifying 14c as a pharmacological tool compound for long-term animal models of MetS.