title: Synthesis of N-alkyl substituted indolocarbazoles as potent inhibitors of human cytomegalovirus replication.
abstract: The synthesis and antiviral evaluation of unsymmetrical indolocarbazole derivatives of Arcyriaflavin A, substituted with a range of alkyl groups at the indole nitrogen, is described. Structure-activity relationships in this series against human cytomegalovirus (HCMV) replication in cell culture are reported. Compound 4b was identified as potent inhibitor of HCMV (IC(50)=19 nM), which retained activity against a range of HCMV strains including ganciclovir resistant isolates.
authors.affiliation: GlaxoSmithKline Medicines Research Centre, Gunnels Wood Road, SG1 2NY, Stevenage, UK. mjs40312@glaxowellcome.co.uk
authors.forename: M J
authors.initials: MJ
authors.lastname: Slater
authors.forename: R
authors.initials: R
authors.lastname: Baxter
authors.forename: R W
authors.initials: RW
authors.lastname: Bonser
authors.forename: S
authors.initials: S
authors.lastname: Cockerill
authors.forename: K
authors.initials: K
authors.lastname: Gohil
authors.forename: N
authors.initials: N
authors.lastname: Parry
authors.forename: E
authors.initials: E
authors.lastname: Robinson
authors.forename: R
authors.initials: R
authors.lastname: Randall
authors.forename: C
authors.initials: C
authors.lastname: Yeates
authors.forename: W
authors.initials: W
authors.lastname: Snowden
authors.forename: A
authors.initials: A
authors.lastname: Walters
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D002227:Carbazoles / Q000138:chemical synthesis / Q000494:pharmacology*; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000187:drug effects*; D004351:Drug Resistance / Q000235:genetics / Q000502:physiology; D015774:Ganciclovir / Q000494:pharmacology; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D013329:Structure-Activity Relationship; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D002227:Carbazoles; D007211:Indoles; C089657:arcyriaflavin A; D011493:Protein Kinase C; D015774:Ganciclovir