Synthesis of 6-substituted 9-benzyl-8-hydroxypurines with potential interferon-inducing activity.
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.
Kazaoka
Kazunori
K
Laboratory of Medicinal Chemistry, Gifu Pharmaceutical University, Mitahora-higashi, Japan.
Sajiki
Hironao
H
Hirota
Kosaku
K
D000818:Animals; D001593:Benzyl Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D002478:Cells, Cultured; D007202:Indicators and Reagents; D007369:Interferon Inducers / Q000138:chemical synthesis* / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D051379:Mice; D008809:Mice, Inbred C3H; D011687:Purines / Q000138:chemical synthesis* / Q000494:pharmacology; D013055:Spectrophotometry, Infrared; D013056:Spectrophotometry, Ultraviolet; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D013329:Structure-Activity Relationship
D001593:Benzyl Compounds; D007202:Indicators and Reagents; D007369:Interferon Inducers; D011687:Purines