1-(triphenylmethyl)-5-(methoxycarbonyl)-1,4,5,6-tetrahydropyrimidine | 146422-24-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: 1-(triphenylmethyl)-5-(methoxycarbonyl)-1,4,5,6-tetrahydropyrimidine
• 英文别名: 1-(triphenylmethyl)-5-(methyloxycarbonyl)-1,4,5,6-tetrahydropyrimidine；1-(trityl)-(5-methyloxycarbonyl)-1,4,5,6-tetrahydropyrimidine；1-Triphenylmethyl-1,4,5,6-tetrahydro-5-methoxycarbonylpyrimidine；1-Triphenylmethyl-5-methoxycarbonyl-1,4,5,6-tetrahydropyrimidine；methyl 1-trityl-5,6-dihydro-4H-pyrimidine-5-carboxylate
• CAS: 146422-24-4
• 化学式: C₂₅H₂₄N₂O₂
• 分子量: 384.478
• InChiKey: HQGGSIOZGDIAIH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  41.9
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(triphenylmethyl)-5-(methoxycarbonyl)-1,4,5,6-tetrahydropyrimidine 在 sodium hydride 作用下， 反应 43.0h， 生成 1,4,5,6-tetrahydro-5-(3-hexyl-1,2,4-oxadiazol-5-yl)pyrimidine 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
• 作为产物：
  描述：

  5-(methoxycarbonyl)-1,4,5,6-tetrahydropyrimidine hydrochloride 以71的产率得到1-(triphenylmethyl)-5-(methoxycarbonyl)-1,4,5,6-tetrahydropyrimidine
  参考文献：
  名称：

  J. Med. Chem. 1993, 36, 842-847

  摘要：

  DOI：

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.

  揭示了替代的1,4,5,6-四氢嘧啶组合物、替代的1,2,3,6-四氢嘧啶组合物和替代的3,4,5,6-四氢吡啶组合物。它们可用于刺激肌氨酸受体，例如治疗认知障碍的症状，特别是与乙酰胆碱合成减少和胆碱能细胞退化相关的记忆障碍。
• Synthesis and Biological Characterization of 1,4,5,6-Tetrahydropyrimidine and 2-Amino-3,4,5,6-tetrahydropyridine Derivatives as Selective m1 Agonists
  作者：William S. Messer,、Yahaya F. Abuh、Yang Liu、Sumudra Periyasamy、Dan O. Ngur、Michael A. N. Edgar、Afif A. El-Assadi、Sbeih、Philip G. Dunbar、Scott Roknich、Taikyun Rho、Zheng Fang、Babatunde Ojo、Hao Zhang、James J. Huzl、Peter I. Nagy

  DOI：10.1021/jm960467d

  日期：1997.4.1

  Previous studies identified several novel tetrahydropyrimidine derivatives exhibiting muscarinic agonist activity in rat brain. Such compounds might be useful in treating cognitive and memory deficits associated with low acetylcholine levels, as found in Alzheimer's disease. To determine the molecular features of ligands important for binding and activity at muscarinic receptor subtypes, the series of tetrahydropyrimidines was extended. Several active compounds were examined further for functional selectivity through biochemical studies of muscarinic receptor activity using receptor subtypes expressed in cell lines. Several amidine derivatives displayed high efficacy at m1 receptors and lower activity at m3 receptors coupled to phosphoinositide (PI) metabolism in A9 L cells. Four ligands, including 1b, 1f, 2b, and 7b, exhibited marked functional selectivity for m1 vs m3 receptors. Compound 1f also exhibited low activity at m2 receptors coupled to the inhibition of adenylyl cyclase in A9 L cells. Molecular modeling studies also were initiated to help understand the nature of the interaction of muscarinic agonists with the m1 receptor using a nine amino model of the m1 receptor. Several important interactions were identified, including interactions between the ester moiety and Thr192. Additional interactions were found for oxadiazoles and alkynyl derivatives with Asn382, suggesting that enhanced potency and selectivity may be achieved by maximizing interactions with Asp105, Thr192, and Asn382. Taken together, the data indicate that several amidine derivatives display functional selectivity for m1 muscarinic receptors, warranting further evaluation as therapeutic agents for the treatment of Alzheimer's disease. In addition, several amino acid residues were identified as potential binding sites for m1 agonists. These data may be useful in directing efforts to develop even more selective m1 agonists.
• Org. Process Res. Dev. 2011, 15, 1344-1347
  作者：

  DOI：——

  日期：——
• Dunbar Philip G., Durant Graham J., Fang Zheng, Abuh Yahaya F., El-Assadi+, J. Med. Chem., 36 (1993) N 7, S 842-847
  作者：Dunbar Philip G., Durant Graham J., Fang Zheng, Abuh Yahaya F., El-Assadi+

  DOI：——

  日期：——
• MUSCARINIC AGONISTS
  申请人：THE UNIVERSITY OF TOLEDO

  公开号：EP0630244A1

  公开（公告）日：1994-12-28