Synthesis of 6-Substituted 9-Benzyl-8-hydroxypurines with Potential Interferon-Inducing Activity

Abstract

Various 6-substituted 9-benzyl-8-hydroxypurines were synthesized in order to investigate the structure–activity relationship at the 6-position of 9-benzyl-8-hydroxyadenine (1), which is a lead compound for the screening of interferon (IFN)-inducing activity. 6-Unsubstituted, mercapto-, methylthio- and hydroxy-9-benzyl-8-hydroxypurines (2—5) were prepared from 5-amino-1-benzyl-4-cyano-2-hydroxyimidazole (9). Synthesis of a 6-methoxy analog (6) was conducted from 5-amino-4-benzylamino-6-chloropyrimidine (13). 6-Alkylamino and acylaminopurines (7 and 8) were also prepared by alkylation and acylation of 1, respectively. Since these compounds (2—8) indicated no activity, it was found that a free amino group of 1 is required for the expression of IFN-inducing activity.