12-benzyl-4-(1H-pyrrol-2-yl)-3,5,6,8,12-pentazatricyclo[7.4.0.02,6]trideca-1(9),2,4-trien-7-one | 135481-50-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶并嘧啶类
• 英文名称: 12-benzyl-4-(1H-pyrrol-2-yl)-3,5,6,8,12-pentazatricyclo[7.4.0.02,6]trideca-1(9),2,4-trien-7-one
• CAS: 135481-50-4
• 化学式: C₁₉H₁₈N₆O
• 分子量: 346.392
• InChiKey: JTMIYINXPFHEQM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  78.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  双(2-氰基乙基)胺 在 potassium tert-butylate 、 sodium ethanolate 、 碳酸氢钠 作用下， 以 乙醇 、 叔丁醇 为溶剂， 反应 38.0h， 生成 12-benzyl-4-(1H-pyrrol-2-yl)-3,5,6,8,12-pentazatricyclo[7.4.0.02,6]trideca-1(9),2,4-trien-7-one
  参考文献：
  名称：

  Anxiolytic properties of certain annelated [1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-ones

  摘要：

  Modification of the benzodiazepine (BZ) receptor binding template 2-aryl[1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one by replacement of the annelated benzene ring with various alicyclic and heterocyclic moieties led to novel structures with potent BZ receptor binding affinity. High affinity was found in some cycloalkyl-annelated [1,2,4]triazolo-[1,5-c]pyrimidin-5(6H)-ones and in some 7,8,9,10-tetrahydropyrido[3,4-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-ones, in which the degree of activity was strongly dependent on the N-substituent in the 9-position. Nine compounds with BZ receptor IC50 binding affinity values equal or superior to diazepam were evaluated in secondary screening. One of these, 9-benzyl-2-phenyl-7,8,9,10-tetrahydropyrido[3,4-e]?? [1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one, showed good activity in rats as a potential anxiolytic agent without sedative liability. However, it increased the rotorod deficit produced by ethanol at anxiolytic doses, an indication of alcohol interaction. Thus, none of the compounds showed an advantage over CGS 9896 (Yokoyama et al. J. Med. Chem. 1982, 25, 337-339), which is free of sedative and alcohol interaction potential as measured by the test procedures described.

  DOI：

  10.1021/jm00113a032

文献信息

• FRANCIS, JOHN E.
  作者：FRANCIS, JOHN E.

  DOI：——

  日期：——
• 2-Substituted-e-fused-[1,2,4]-triazolo[1,5-c] pyrimidines, pharmaceutical compositions, and uses thereof
  申请人：CIBA-GEIGY AG

  公开号：EP0263071B1

  公开（公告）日：1992-08-12
• Anxiolytic properties of certain annelated [1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-ones
  作者：John E. Francis、Debra A. Bennett、James L. Hyun、Stephen L. Rovinski、Caryl L. Amrick、Patricia S. Loo、Deborah Murphy、Robert F. Neale、Douglas E. Wilson

  DOI：10.1021/jm00113a032

  日期：1991.9

  Modification of the benzodiazepine (BZ) receptor binding template 2-aryl[1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one by replacement of the annelated benzene ring with various alicyclic and heterocyclic moieties led to novel structures with potent BZ receptor binding affinity. High affinity was found in some cycloalkyl-annelated [1,2,4]triazolo-[1,5-c]pyrimidin-5(6H)-ones and in some 7,8,9,10-tetrahydropyrido[3,4-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-ones, in which the degree of activity was strongly dependent on the N-substituent in the 9-position. Nine compounds with BZ receptor IC50 binding affinity values equal or superior to diazepam were evaluated in secondary screening. One of these, 9-benzyl-2-phenyl-7,8,9,10-tetrahydropyrido[3,4-e]?? [1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one, showed good activity in rats as a potential anxiolytic agent without sedative liability. However, it increased the rotorod deficit produced by ethanol at anxiolytic doses, an indication of alcohol interaction. Thus, none of the compounds showed an advantage over CGS 9896 (Yokoyama et al. J. Med. Chem. 1982, 25, 337-339), which is free of sedative and alcohol interaction potential as measured by the test procedures described.