5-(3-methyl-1,2,4-oxadiazol-5-yl)-1,4,5,6-tetrahydropyrimidine trifluoroacetate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 5-(3-methyl-1,2,4-oxadiazol-5-yl)-1,4,5,6-tetrahydropyrimidine trifluoroacetate
• 英文别名: CDD-0098 trifluoroacetate；1,4,5,6-Tetrahydro-5-(3-methyl-1,2,4-oxadiazol-5-yl)pyrimidine trifluoroacetate；3-methyl-5-(1,4,5,6-tetrahydropyrimidin-5-yl)-1,2,4-oxadiazole;2,2,2-trifluoroacetic acid
• 化学式: C₂HF₃O₂*C₇H₁₀N₄O
• 分子量: 280.207
• InChiKey: VNNPKITYMMVTIG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.73
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  101
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  1-(triphenylmethyl)-5-(methoxycarbonyl)-1,4,5,6-tetrahydropyrimidine 在 sodium hydride 作用下， 反应 43.0h， 生成 5-(3-methyl-1,2,4-oxadiazol-5-yl)-1,4,5,6-tetrahydropyrimidine trifluoroacetate
  参考文献：
  名称：

  Design, synthesis, and neurochemical evaluation of 5-(3-alkyl-1,2,4-oxadiazol-5-yl)-1,4,5,6-tetrahydropyrimidines as M1 muscarinic receptor agonists

  摘要：

  A series of 5-(3-alkyl-1,2,4-oxadiazol-5-yl)-1,4,5,6-tetrahydropyrimidines (7a-h) was synthesized for biological evaluation as selective agonists for M1 receptors coupled to phosphoinositide (PI) metabolism in the central nervous system. Each ligand bound with high affinity to muscarinic receptors from rat brain as measured by inhibition of [H-3]-(R)-quinuclidinyl benzilate ([H-3]-(R)-QNB)binding. 5-(3-Methyl-1,2,4-oxadiazol-5-yl)-1,4,5,6-tetrahydropyrimidine trifluoroacetate (CDD-0098-J; 7a) displayed high affinity (IC50 = 2.7 +/- 0.69 muM) and efficacy at muscarinic receptors coupled to PI metabolism in the rat cortex and hippocampus. Increasing the length of the alkyl substituent increased affinity for muscarinic receptors yet decreased activity in PI turnover assays. The hippocampal PI response of 7a was blocked by lower concentrations of pirenzepine (8) or by higher concentrations of either AF-DX 116 (9) or p-fluorohexahydrosiladifenidol (10), suggesting that at low concentrations 7a selectively stimulates PI turnover through M1 receptors.

  DOI：

  10.1021/jm00059a008

文献信息

• Muscarinic agonists
  申请人：The University of Toledo

  公开号：US05175166A1

  公开（公告）日：1992-12-29

  Substituted 1,4,5,6 -tetrahydropyrimidine compositions, substituted 1,2,3,6-tetrahydropyrimidine compositions and substituted 3,4,5,6-tetrahydropyridine compositions are disclosed. They are useful for stimulating muscarinic receptors including, for example, treating the symptoms of cognitive disorders, especially impared memory, which are associated with decreased acetylcholine synthesis and cholinergic cell degeneration.

  本文介绍了1,4,5,6-四氢嘧啶组合物、1,2,3,6-四氢嘧啶组合物和3,4,5,6-四氢吡啶组合物。它们可用于刺激毒蕈碱受体，包括治疗与乙酰胆碱合成减少和胆碱能细胞退化相关的认知障碍症状，特别是受损的记忆。
• MUSCARINIC AGONISTS
  申请人：THE UNIVERSITY OF TOLEDO

  公开号：EP0630244A1

  公开（公告）日：1994-12-28
• EP0630244A4
  申请人：——

  公开号：EP0630244A4

  公开（公告）日：1994-04-07
• US5175166A
  申请人：——

  公开号：US5175166A

  公开（公告）日：1992-12-29
• US5403845A
  申请人：——

  公开号：US5403845A

  公开（公告）日：1995-04-04