1-propyl-8-phenylxanthine

• 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: 1-propyl-8-phenylxanthine
• 英文别名: 8-Phenyl-1-propyl-3,7-dihydro-purine-2,6-dione；8-phenyl-1-propyl-3,7-dihydropurine-2,6-dione
• 化学式: C₁₄H₁₄N₄O₂
• 分子量: 270.291
• InChiKey: LNATVXLECNOWHK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  78.1
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  5,6-二氨基-3-丙基嘧啶-2,4(1h,3h)-二酮 在 氯化亚砜 作用下， 以 乙醇 为溶剂， 反应 1.0h， 生成 1-propyl-8-phenylxanthine
  参考文献：
  名称：

  1,8-Disubstituted Xanthine Derivatives:  Synthesis of Potent A_2B-Selective Adenosine Receptor Antagonists

  摘要：

  3-Unsubstituted xanthine derivatives bearing a cyclopentyl or a phenyl residue in the 8-position were synthesized and developed as A(2)B adenosine receptor antagonists. Compounds bearing polar substituents were prepared to obtain water-soluble derivatives. 1-Alkyl-8-phenylxanthine derivatives were found to exhibit high affinity for A(2B) adenosine receptors (ARs). 1,8-Disubstituted xanthine derivatives were equipotent to or more potent than 1,3,8-trisubstituted xanthines at A(2B) ARs, but generally less potent at A(1) and A(2A), and much less potent at A(3) ARs. Thus, the new compounds exhibited increased A2B selectivity versus all other AR subtypes. 9-Deazaxanthines (pyrrolo[2,3-d]pyrimidindiones) appeared to be less potent at A(2B) ARs than the corresponding xanthine derivatives. 1-Propyl-8-p-sulfophenylxanthiiie (17) was the most selective compound of the present series, exhibiting a K-i value of 53 nM at human A(2B) ARs and showing greater than 180-fold selectivity versus human A, ARs. Compound 17 was also highly selective versus rat A, ARs (41-fold) and versus the other human AR subtypes (A(2A) > 400-fold and A3 > 180-fold). The compound is highly water-soluble due to its sulfonate function. 1-Butyl-8-p-carboxyphenylxanthine (10), another polar analogue bearing a carboxylate function, exhibited a K-i value of 24 nM for A(2B) ARs, 49-fold selectivity versus human and 20-fold selectivity versus rat A, ARs, and greater than 150-fold selectivity versus human A2A and A3 ARs. 8-[4-(2-Hydroxyethylamino)-2-oxoethoxy)phenyl]-1-propylxanthine (29) and 1-butyl-8-[4(4-benzyl)piperazino-2-oxoethoxy)phenyl]xanthine (35) were among the most potent A(2B) antagonists showing K-i values at A(2B) ARs of 1 nM, 57-fold (29) and 94-fold (35) selectivity versus human A(1), ca. 30-fold selectivity versus rat A(1), and greater than 400-fold selectivity versus human A(2A) and A(3) ARs. The new potent, selective, water-soluble A(2B) antagonists may be useful research tools for investigating A(2B) receptor function.

  DOI：

  10.1021/jm011049y

文献信息

• Effects of 8-phenyl and 8-cycloalkyl substituents on the activity of mono-, di, and trisubstituted alkylxanthines with substitution at the 1-, 3-, and 7-positions
  作者：Mah T. Shamim、Dieter Ukena、William L. Padgett、John W. Daly

  DOI：10.1021/jm00126a014

  日期：1989.6

  The effects of 8-phenyl and 8-cycloalkyl substituents on the activity of theophylline, caffeine, 1,3-dipropylxanthine, 1,3-dipropyl-7-methylxanthine, 3-propylxanthine, and 1-propylxanthine at A1 adenosine receptors of rat brain and fat cells and at A2 adenosine receptors of rat pheochromocytoma PC12 cells and human platelets are compared. An 8-phenyl substituent has little effect on the activity of

  8-苯基和8-环烷基取代基对大鼠脑A1腺苷受体上茶碱，咖啡因，1,3-二丙基黄嘌呤，1,3-二丙基-7-甲基黄嘌呤，3-丙基黄嘌呤和1-丙基黄嘌呤活性的影响比较了大鼠嗜铬细胞瘤PC12细胞和人血小板的脂肪细胞和A2腺苷受体。8-苯基取代基对咖啡因或1,3-二丙基-7-甲基黄嘌呤在腺苷受体上的活性几乎没有影响，而茶碱，1,3-二丙基黄嘌呤，1-异戊基-3-异丁基黄嘌呤，1-甲基黄嘌呤和3-丙基黄嘌呤。8-苯基-1-丙基黄嘌呤在所有受体上均有效（Ki = 20-70 nM）。对羧基或对磺基取代基，它被引入8-苯环以增加水溶性，在大多数情况下，会降低A1受体的活性和选择性。在8-对-磺基类似物中，只有8-（对-磺基苯基）茶碱和1，3-二丙基-8-（对-磺基苯基）黄嘌呤对A1受体具有选择性。咖啡因，1，3-二丙基-7-甲基黄嘌呤和3-丙基黄嘌呤的8-对-磺基苯基衍生物对A2受体具有一定的选择性。8
• SHAMIM, MAH T.;UKENA, DIETER;PADGETT, WILLIAM L.;DALY, JOHN W., J. MED. CHEM., 32,(1989) N, C. 1231-1237
  作者：SHAMIM, MAH T.、UKENA, DIETER、PADGETT, WILLIAM L.、DALY, JOHN W.

  DOI：——

  日期：——