Adenosine deaminase inhibitors. Synthesis of deaza analogs of erythro-9-(2-hydroxy-3-nonyl) adenine
作者:Ippolito Antonini、Gloria Cristalli、Palmarisa Franchetti、Mario Grifantini、Sante Martelli、Giulio Lupidi、Francesca Riva
DOI:10.1021/jm00369a008
日期:1984.3
Structural analogues of erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA), in which the adenine moiety of the molecule was modified, were prepared in order to investigate the structural requirement of EHNA as an inhibitor of adenosine deaminase (ADA). Thus, 1- and 3-deaza-EHNA and their 6-deamino analogues were synthesized and evaluated as inhibitors of ADA from calf intestine. Inhibition studies indicated
为了研究EHNA作为腺苷脱氨酶抑制剂的结构要求,制备了erythro-9-(2-羟基-3-壬基)腺嘌呤(EHNA)的结构类似物,其中修饰了该分子的腺嘌呤部分( ADA)。因此,合成了1-和3-脱氮-EHNA及其6-脱氨基类似物,并将其评价为来自小牛肠的ADA的抑制剂。抑制研究表明,在酶结合位点可以容忍嘧啶氮被碳等位取代。实际上,发现3-deaza-EHNA具有与EHNA本身相当的抑制活性,并且1-deaza-EHNA尽管效力较弱,但却是良好的抑制剂。如果还存在N1氮,则6-氨基基团对酶促结合起重要作用,从而使该化合物具有半密封抑制剂的特性。