8-Cyclohexylmethyl-1,3-dipropyl-3,7-dihydro-purine-2,6-dione | 112683-73-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: 8-Cyclohexylmethyl-1,3-dipropyl-3,7-dihydro-purine-2,6-dione
• 英文别名: 8-(cyclohexylmethyl)-1,3-dipropyl-7H-purine-2,6-dione
• CAS: 112683-73-5
• 化学式: C₁₈H₂₈N₄O₂
• 分子量: 332.446
• InChiKey: RQIMFOZIUJUKKB-UHFFFAOYSA-N

物化性质

• 熔点：
  137-138 °C
• 沸点：
  547.3±42.0 °C(Predicted)
• 密度：
  1.160±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.72
• 拓扑面积：
  69.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  环己基乙酸 在 sodium hydroxide 、 N,N'-二异丙基碳二亚胺 作用下， 以 甲醇 、 乙醇 为溶剂， 反应 0.58h， 生成 8-Cyclohexylmethyl-1,3-dipropyl-3,7-dihydro-purine-2,6-dione
  参考文献：
  名称：

  8-Aryl- and 8-cycloalkyl-1,3-dipropylxanthines: further potent and selective antagonists for A1-adenosine receptors

  摘要：

  A series of 1,3-dipropylxanthines were prepared with a variety of substituents at the 8-position. These included 8-aryl and 8-cycloalkyl groups. Polar carboxylate and carboxamide moieties were introduced as aryl substituents to increase water solubility. 1,3-Dipropyl-8-[2-hydroxy-4-[(carboxymethyl)oxy]phenyl]xanthine provided a functionalized congener with high potency (Ki = 37 nM) and selectivity (54-fold) for A1-adenosine receptors. This congener was used for preparation of a series of other analogues, some with higher potency and some with higher selectivity. 8-Cyclopentyl- and 8-cyclohexyl-1,3-dipropylxanthines were both very potent (Ki = 1-1.5 nM) and selective for A1 receptors, while 8-cycloalkylmethyl analogues were 10-fold less potent, but still very selective for A1 receptors. 8-Piperidinyl and 8-pyrazinyl analogues had very low activities as adenosine receptor antagonists.

  DOI：

  10.1021/jm00398a020

文献信息

• 8-Aryl- and 8-cycloalkyl-1,3-dipropylxanthines: further potent and selective antagonists for A1-adenosine receptors
  作者：M. T. Shamim、D. Ukena、W. L. Padgett、O. Hong、J. W. Daly

  DOI：10.1021/jm00398a020

  日期：1988.3

  A series of 1,3-dipropylxanthines were prepared with a variety of substituents at the 8-position. These included 8-aryl and 8-cycloalkyl groups. Polar carboxylate and carboxamide moieties were introduced as aryl substituents to increase water solubility. 1,3-Dipropyl-8-[2-hydroxy-4-[(carboxymethyl)oxy]phenyl]xanthine provided a functionalized congener with high potency (Ki = 37 nM) and selectivity (54-fold) for A1-adenosine receptors. This congener was used for preparation of a series of other analogues, some with higher potency and some with higher selectivity. 8-Cyclopentyl- and 8-cyclohexyl-1,3-dipropylxanthines were both very potent (Ki = 1-1.5 nM) and selective for A1 receptors, while 8-cycloalkylmethyl analogues were 10-fold less potent, but still very selective for A1 receptors. 8-Piperidinyl and 8-pyrazinyl analogues had very low activities as adenosine receptor antagonists.
• SHAMIM, M. T.;UKENA, D.;PADGETT, W. L.;HONG, O.;DALY, J. W., J. MED. CHEM., 31,(1988) N 3, 613-617
  作者：SHAMIM, M. T.、UKENA, D.、PADGETT, W. L.、HONG, O.、DALY, J. W.

  DOI：——

  日期：——
• 8-Polycycloalkyl-1,3-dipropylxanthines as potent and selective antagonists for A1-adenosine receptors
  作者：Junichi Shimada、Fumio Suzuki、Hiromi Nonaka、Akio Ishii

  DOI：10.1021/jm00083a018

  日期：1992.3

  With the aim of characterizing the hydrophobic interactions between xanthines and the A1 receptor site, 1,3-dipropyl-8-substituted xanthines were synthesized. Introduction of a quaternary carbon and the conformationally restricted cyclopentyl moiety into the 8-position of xanthines enhanced the adenosine A1 antagonism. 1,3-Dipropyl-8-(3-noradamantyl)xanthine (42) was identified to be a selective and the most potent A1 receptor antagonist reported to date. Under our structure-activity relationship, the 8-substituent of xanthine antagonists and the N6-substituent of adenosine agonists appears to bind to the same region of the A1 receptor.