2-(4-Trifluoromethylphenyl)pyrimidine-5-boronic acid pinacol ester | 1402233-87-7

• 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: 2-(4-Trifluoromethylphenyl)pyrimidine-5-boronic acid pinacol ester
• 英文别名: 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-[4-(trifluoromethyl)phenyl]pyrimidine
• CAS: 1402233-87-7
• 化学式: C₁₇H₁₈BF₃N₂O₂
• 分子量: 350.148
• InChiKey: POBOBOJUBLVROR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.46
• 重原子数：
  25
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  44.2
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2-(4-Trifluoromethylphenyl)pyrimidine-5-boronic acid pinacol ester 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 potassium phosphate 、 N-羟基-7-氮杂苯并三氮唑 、 C₃H₇ClMg*Li⁽¹⁺⁾*Cl^(1-) 、 对甲苯磺酸 、 1,2-二氯乙烷 、 三乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 乙二醇二甲醚 、 乙醇 、 二氯甲烷 、 水 、 甲苯 为溶剂， 反应 31.5h， 生成 ethyl 3-(4-((1R,2R)-2-(2-(4-(trifluoromethyl)phenyl)pyrimidin-5-yl)cyclopentyl)benzamido)propanoate
  参考文献：
  名称：

  Identification of a novel conformationally constrained glucagon receptor antagonist

  摘要：

  Identification of orally active, small molecule antagonists of the glucagon receptor represents a novel treatment paradigm for the management of type 2 diabetes mellitus. The present work discloses novel glucagon receptor antagonists, identified via conformational constraint of current existing literature antagonists. Optimization of lipophilic ligand efficiency (LLE or LipE) culminated in enantiomers (+)-trans-26 and (-)-trans-27 which exhibit good physicochemical and in vitro drug metabolism profiles. In vivo, significant pharmacokinetic differences were noted with the two enantiomers, which were primarily driven through differences in clearance rates. Enantioselective oxidation by cytochrome P450 was ruled out as a causative factor for pharmacokinetic differences. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.12.090
• 作为产物：
  描述：

  5-bromo-2-(4-(trifluoromethyl)phenyl)pyrimidine 、 联硼酸频那醇酯 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 potassium acetate 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 以84%的产率得到2-(4-Trifluoromethylphenyl)pyrimidine-5-boronic acid pinacol ester
  参考文献：
  名称：

  Identification of a novel conformationally constrained glucagon receptor antagonist

  摘要：

  Identification of orally active, small molecule antagonists of the glucagon receptor represents a novel treatment paradigm for the management of type 2 diabetes mellitus. The present work discloses novel glucagon receptor antagonists, identified via conformational constraint of current existing literature antagonists. Optimization of lipophilic ligand efficiency (LLE or LipE) culminated in enantiomers (+)-trans-26 and (-)-trans-27 which exhibit good physicochemical and in vitro drug metabolism profiles. In vivo, significant pharmacokinetic differences were noted with the two enantiomers, which were primarily driven through differences in clearance rates. Enantioselective oxidation by cytochrome P450 was ruled out as a causative factor for pharmacokinetic differences. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.12.090

文献信息

• Identification of a novel conformationally constrained glucagon receptor antagonist
  作者：Esther C.Y. Lee、Meihua Tu、Benjamin D. Stevens、Jianwei Bian、Gary Aspnes、Christian Perreault、Matthew F. Sammons、Stephen W. Wright、John Litchfield、Amit S. Kalgutkar、Raman Sharma、Mary T. Didiuk、David C. Ebner、Kevin J. Filipski、Janice Brown、Karen Atkinson、Jeffrey A. Pfefferkorn、Angel Guzman-Perez

  DOI：10.1016/j.bmcl.2013.12.090

  日期：2014.2

  Identification of orally active, small molecule antagonists of the glucagon receptor represents a novel treatment paradigm for the management of type 2 diabetes mellitus. The present work discloses novel glucagon receptor antagonists, identified via conformational constraint of current existing literature antagonists. Optimization of lipophilic ligand efficiency (LLE or LipE) culminated in enantiomers (+)-trans-26 and (-)-trans-27 which exhibit good physicochemical and in vitro drug metabolism profiles. In vivo, significant pharmacokinetic differences were noted with the two enantiomers, which were primarily driven through differences in clearance rates. Enantioselective oxidation by cytochrome P450 was ruled out as a causative factor for pharmacokinetic differences. (C) 2014 Elsevier Ltd. All rights reserved.