640274-18-6Relevant articles and documents
Synthesis and structure-activity relationships of 2-substituted-8-hydroxyadenine derivatives as orally available interferon inducers without emetic side effects
Isobe, Yoshiaki,Tobe, Masanori,Ogita, Haruhisa,Kurimoto, Ayumu,Ogino, Tetsuhiro,Kawakami, Hajime,Takaku, Haruo,Sajiki, Hironao,Hirota, Kosaku,Hayashi, Hideya
, p. 3641 - 3647 (2007/10/03)
Recently we reported the adenine derivatives (2-4) as new interferon (IFN) inducers. In the present study, we conducted a detailed structure and activity relationship study of 4 and its related derivatives on IFN inducing activity. From this study, we found that compound 4 exhibited the most potent IFN inducing activity in vitro with a minimum effective concentration of 0.01 μM, and 4 also showed strong IFN-inducing activity at doses of more than 0.3 mg/kg by oral administration in mice. This potency was 10-fold stronger than that of Imiquimod. Moreover, 4 did not cause emesis in ferrets even at doses as high as 10 mg/kg, whereas, 80% of animals were emetic when orally administered with the same dose of Imiquimod. These results indicate that compound 4 is superior to Imiquimod with respect to efficacy and safety.
