Discovery of 8-hydroxyadenines as a novel type of interferon inducer.
9-Benzyl-8-hydroxyadenine (6) was found to possess interferon-inducing activity in vitro as a lead compound. Although replacement of the 9-benzyl group of 6 did not improve the activity, the introduction of a substituent such as alkyl, alkylthio, alkylamino, and alkoxy groups into the 2-position of the adenine ring resulted in a remarkable increase in the activity. The 2-alkylthio (30-32), 2-butylamino (41), and 2-butoxy (47) analogues indicated the highest activities by oral administration to mice.
Hirota
Kosaku
K
Laboratory of Medicinal Chemistry, Gifu Pharmaceutical University, Mitahora-higashi, Gifu 502-8585, Japan. hirota@gifu-pu.ac.jp
Kazaoka
Kazunori
K
Niimoto
Itaru
I
Kumihara
Hiroshi
H
Sajiki
Hironao
H
Isobe
Yoshiaki
Y
Takaku
Haruo
H
Tobe
Masanori
M
Ogita
Haruhisa
H
Ogino
Tetsuhiro
T
Ichii
Shinji
S
Kurimoto
Ayumu
A
Kawakami
Hajime
H
D000225:Adenine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D000284:Administration, Oral; D000818:Animals; D066298:In Vitro Techniques; D007369:Interferon Inducers / Q000138:chemical synthesis* / Q000494:pharmacology; D051379:Mice; D013154:Spleen / Q000166:cytology; D013329:Structure-Activity Relationship
D007369:Interferon Inducers; D000225:Adenine