Castagnino E, Salvatori A, Corsano S, Tacchi P, Martini C, Lucacchini A
Institute of Medicinal Chemistry, University of Urbino, Italy.
Drug Des Discov. 1995 Apr;12(4):313-21.
The activity of a series of 1,3-dipropyl-xanthines bearing C8-cycloalkyl substituents as antagonists at A1 and A2 adenosine receptors is examined. Pharmacological results showed that the size of the 8-substituent is an important feature for response in activity of such class of antagonists. Among compounds 3-8, the 2-norbornyl analog 6 showed the best A1/A2 selectivity. A new route for the synthesis of 8-alkyl-substituted xanthines is presented. This method, consisting of a direct alkylation of the imidazole moiety through a radical mechanism reaction, was shown to be a more convenient strategy in comparison with the commonly employed synthetic schemes.
研究了一系列带有C8 - 环烷基取代基的1,3 - 二丙基黄嘌呤作为A1和A2腺苷受体拮抗剂的活性。药理学结果表明，8 - 取代基的大小是这类拮抗剂活性响应的一个重要特征。在化合物3 - 8中，2 - 降冰片基类似物6表现出最佳的A1/A2选择性。提出了一种合成8 - 烷基取代黄嘌呤的新路线。与常用的合成方案相比，这种通过自由基机理反应直接烷基化咪唑部分的方法被证明是一种更方便的策略。
