title: Design, Synthesis, and Evaluation of Anti-HBV Activity of Hybrid Molecules of Entecavir and Adefovir: Exomethylene Acycloguanine Nucleosides and Their Monophosphate Derivatives.
abstract: Exomethylene acycloguanine nucleosides 4, 6 and its monophosphate derivatives 5, 7, and 8 have been synthesized. Mitsunobu-type coupling of 2-N-acetyl-6-O-diphenylcarbamoylguanine (11) with primary alcohols proceeded regioselectively to furnish the desired N(9)-substituted products in moderate yield. Evaluation of 4-8 for anti-HBV activity in HepG2 cells revealed that the phosphonate derivative 8 was found to exhibit moderated activity (EC50 value of 0.29 μM), but cytotoxicity (CC50 value of 39 μM) against the host cells was also observed.
authors.affiliation: a Faculty of Pharmaceutical Sciences, Sojo University , Nishi-ku , Kumamoto , Japan.
authors.forename: Shuhei
authors.initials: S
authors.lastname: Imoto
authors.forename: Satoru
authors.initials: S
authors.lastname: Kohgo
authors.forename: Ryoh
authors.initials: R
authors.lastname: Tokuda
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kumamoto
authors.forename: Manabu
authors.initials: M
authors.lastname: Aoki
authors.forename: Masayuki
authors.initials: M
authors.lastname: Amano
authors.forename: Nobuyo
authors.initials: N
authors.lastname: Kuwata-Higashi
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Mitsuya
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Haraguchi
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D015195:Drug Design; D006147:Guanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D056945:Hep G2 Cells; D006515:Hepatitis B virus / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D063065:Organophosphonates / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000998:Antiviral Agents; D063065:Organophosphonates; C413685:entecavir; D006147:Guanine; C053001:adefovir; D000225:Adenine
keywords: Nucleoside; acyclonucleoside; adefovir; anti-HBV activity; entecavir; hybrid; nucleoside phosphonate; pro-drug