Biagi Giuliana, Giorgi Irene, Livi Oreste, Nardi Antonio, Pacchini Federica, Scartoni Valerio, Lucacchini Antonio
Dipartimento di Scienze Farmaceutiche, Università di Pisa, via Bonanno, 6-56126 Pisa, Italy.
Eur J Med Chem. 2003 Nov-Dec;38(11-12):983-90. doi: 10.1016/j.ejmech.2003.09.003.
Several 9-benzyl-N6-cycloalkyl-2-phenyladenines, 9-benzyl-N6-cycloalkyl-2-phenyl-8-azaadenines and 4-cycloalkylamino-1-benzyl-6-phenyl-1H-1,2,3-triazolo[4,5-c]pyridines were prepared and assayed as A1 adenosine receptor ligands. The 1H-1,2,3-triazolo[4,5-c]pyridines were obtained starting from N,N-diethyl-1-benzyl-4-carboxyamido-5-methyl-1H-1,2,3-triazole by lithiation in anhydrous tetrahydrofurane in the presence of benzonitrile. The usual work up afforded the isolation of 1-benzyl-6-phenyl-1H-1,2,3-triazolo[4,5-c]pyridin-4-one which was treated with phosphorous oxychloride and cycloalkylamines. Some compounds showed high affinity and selectivity and the trend of Ki values corresponds to the series of 9-benzyl-N6-cycloalkyl-2-phenyladenines and 9-benzyl-N6-cycloalkyl-2-phenyl-8-azaadenines, therefore they can be considered bioisosteres. The affinity data permitted us to ascertain the role and the importance of the N3 in the adenine or 8-azaadenine moiety in the receptor binding and to study the dimension of the receptor lipophilic pocket which is filled by the N6 substituent of adenosine derivatives.
合成了几种9-苄基-N6-环烷基-2-苯基腺嘌呤、9-苄基-N6-环烷基-2-苯基-8-氮杂腺嘌呤和4-环烷基氨基-1-苄基-6-苯基-1H-1,2,3-三唑并[4,5-c]吡啶，并作为A1腺苷受体配体进行了测定。1H-1,2,3-三唑并[4,5-c]吡啶是从N,N-二乙基-1-苄基-4-甲酰胺基-5-甲基-1H-1,2,3-三唑出发，在无水四氢呋喃中，于苄腈存在下进行锂化反应制得的。常规后处理得到1-苄基-6-苯基-1H-1,2,3-三唑并[4,5-c]吡啶-4-酮，将其用三氯氧磷和环烷基胺处理。一些化合物表现出高亲和力和选择性，其Ki值趋势与9-苄基-N6-环烷基-2-苯基腺嘌呤和9-苄基-N6-环烷基-2-苯基-8-氮杂腺嘌呤系列相对应，因此它们可被视为生物电子等排体。亲和力数据使我们能够确定腺嘌呤或8-氮杂腺嘌呤部分中N3在受体结合中的作用和重要性，并研究由腺苷衍生物的N6取代基填充的受体亲脂口袋的尺寸。
