2-chloro-N-((2-methyl-2-azabicyclo[2.2.2]octan-1-yl)(pyridin-3-yl)methyl)-3-(trifluoromethyl)benzamide | 1239321-40-4

• 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-chloro-N-((2-methyl-2-azabicyclo[2.2.2]octan-1-yl)(pyridin-3-yl)methyl)-3-(trifluoromethyl)benzamide
• 英文别名: 2-chloro-N-[(2-methyl-2-azabicyclo[2.2.2]octan-1-yl)-pyridin-3-ylmethyl]-3-(trifluoromethyl)benzamide
• CAS: 1239321-40-4
• 化学式: C₂₂H₂₃ClF₃N₃O
• 分子量: 437.892
• InChiKey: HAEZNAGXRGHZJV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  45.2
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2-chloro-N-((2-methyl-3-oxo-2-azabicyclo[2.2.2]octan-1-yl)(pyridin-3-yl)methyl)-3-(trifluoromethyl)-benzamide 在 三(三苯基膦)羰基氢化铑 二苯基硅烷 作用下， 以 四氢呋喃 为溶剂， 以37.7%的产率得到2-chloro-N-((2-methyl-2-azabicyclo[2.2.2]octan-1-yl)(pyridin-3-yl)methyl)-3-(trifluoromethyl)benzamide
  参考文献：
  名称：

  [EN] 2-AZA-BICYCLO[2.2.2]OCTANE COMPOUNDS AND USES THEREOF
  [FR] COMPOSÉS 2-AZA-BICYCLO[2.2.2]OCTANE ET LEURS UTILISATIONS

  摘要：

  这项发明涉及2-aza-bicyclo [2.2.2]辛烷化合物（及其盐），制备这种化合物的过程以及包含这种化合物的药物组合物。该发明还涉及利用这些化合物调节甘氨酸转运蛋白1（GIyTl）并用于治疗精神病、认知障碍、双相情感障碍、抑郁症、焦虑症、创伤后应激障碍和疼痛。

  公开号：

  WO2010087761A1

文献信息

• Bicyclo((aryl)methyl)benzamides as inhibitors of GlyT1
  作者：Jeffrey G. Varnes、Hui Xiong、Janet M. Forst、Christopher R. Holmquist、Glen E. Ernst、William Frietze、Bruce Dembofsky、Don W. Andisik、William E. Palmer、Lindsay Hinkley、Gary B. Steelman、Deidre E. Wilkins、Gaochao Tian、Gerald Jonak、William M. Potts、Xia Wang、Todd A. Brugel、Cristóbal Alhambra、Michael W. Wood、Chris A. Veale、Jeffrey S. Albert

  DOI：10.1016/j.bmcl.2018.02.029

  日期：2018.4

  A series of isoquinuclidine benzamides as glycine uptake inhibitors for the treatment of schizophrenia are described. Potency, lipophilicity, and intrinsic human microsomal clearance were parameters for optimization. Potency correlated with the nature of the ortho substituents of the benzamide ring, and reductions in lipophilicity could be achieved through heteroatom incorporation in the benzamide and pendant phenyl moieties. Improvements in human CLint were achieved through changes in ring size and the N-alkyl group of the isoquinuclidine itself, with des-alkyl derivatives (40-41, 44) demonstrating the most robust microsomal stability. Dimethylbenzamide 9 was tested in a mouse MK801 LMA assay and had a statistically significant attenuation of locomotor activity at 3 and 10 mu mol/kg compared to control. (C) 2018 Elsevier Ltd. All rights reserved.