2-amino-6-chloro-N-[(R)-(2-methyl-2-aza-bicyclo[2.2.2]oct-1-yl)-phenyl-methyl]-benzamide | 1108615-32-2

• 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-amino-6-chloro-N-[(R)-(2-methyl-2-aza-bicyclo[2.2.2]oct-1-yl)-phenyl-methyl]-benzamide
• 英文别名: 2-amino-6-chloro-N-[(R)-(2-methyl-2-azabicyclo[2.2.2]octan-1-yl)-phenylmethyl]benzamide
• CAS: 1108615-32-2
• 化学式: C₂₂H₂₆ClN₃O
• 分子量: 383.921
• InChiKey: DMUSIJAABIIKCS-YOMPXFNTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  58.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  (R)-2-methyl-N-((2-methyl-3-oxo-2-azabicyclo[2.2.2]octan-1-yl)methylene)propane-2-sulfinamide 在 盐酸 、 二苯基硅烷 、 H(Rh)(CO)(PPh₃)₃ 、 三甲基铝 、 1-羟基苯并三唑 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 乙醚 、 N,N-二甲基甲酰胺 为溶剂， 生成 2-amino-6-chloro-N-[(R)-(2-methyl-2-aza-bicyclo[2.2.2]oct-1-yl)-phenyl-methyl]-benzamide
  参考文献：
  名称：

  Bicyclo((aryl)methyl)benzamides as inhibitors of GlyT1

  摘要：

  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.

  DOI：

  10.1016/j.bmcl.2018.02.029

文献信息

• Novel Compounds 894
  申请人：Albert Jeffrey Scott

  公开号：US20090030033A1

  公开（公告）日：2009-01-29

  The invention relates to 2-aza-bicyclo[2.2.2]octane compounds and uses thereof. Particularly the invention relates to such compounds and their uses as pharmaceuticals in treating pyshoses such as schizophrenia and other diseases, disorders, or conditions.

  该发明涉及2-aza-bicyclo[2.2.2]辛烷化合物及其用途。特别是该发明涉及这些化合物及其在治疗精神分裂症等疾病、障碍或症状中的药用用途。
• 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.