title: Synthesis and structure-activity relationships of 2-amino-8-hydroxyadenines as orally active interferon inducing agents.
abstract: Recently, we have reported the 8-hydroxyadenine derivatives (2-4) as a novel class of interferon (IFN) inducing agents. In the present study, a series of 8-hydroxyadenines, which possess various amino moieties at the adenine C(2)-position, were synthesized and evaluated for their ability to induce endogenous IFN in comparison to the known active agent, Imiquimod. Among the compounds prepared, compound 9o possessing a 2-methoxyethylamino group at C(2)-position of adenine was found to exhibit potent IFN inducing activity in vivo. Compound 9o induced IFN from the dosage of 0.1 mg/kg, which was 30-fold potent than that of Imiquimod, and showed a good oral bioavailability (F=81%).
authors.affiliation: Research Division, Discovery Research Laboratories II, Sumitomo Pharmaceuticals Co Ltd, Konohana-ku, Osaka 554-0022, Japan. akurimoto@sumitomopharm.co.jp
authors.forename: Ayumu
authors.initials: A
authors.lastname: Kurimoto
authors.forename: Tetsuhiro
authors.initials: T
authors.lastname: Ogino
authors.forename: Shinji
authors.initials: S
authors.lastname: Ichii
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Isobe
authors.forename: Masanori
authors.initials: M
authors.lastname: Tobe
authors.forename: Haruhisa
authors.initials: H
authors.lastname: Ogita
authors.forename: Haruo
authors.initials: H
authors.lastname: Takaku
authors.forename: Hironao
authors.initials: H
authors.lastname: Sajiki
authors.forename: Kosaku
authors.initials: K
authors.lastname: Hirota
authors.forename: Hajime
authors.initials: H
authors.lastname: Kawakami
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D000284:Administration, Oral; D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D000077271:Imiquimod; D007369:Interferon Inducers / Q000138:chemical synthesis* / Q000494:pharmacology; D007372:Interferons / Q000032:analysis / Q000096:biosynthesis*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D015394:Molecular Structure; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000634:Aminoquinolines; D007369:Interferon Inducers; C002992:8-hydroxyadenine; D007372:Interferons; D000225:Adenine; D000077271:Imiquimod