Synthesis of N-alkyl substituted indolocarbazoles as potent inhibitors of human cytomegalovirus replication.
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.
Slater
M J
MJ
GlaxoSmithKline Medicines Research Centre, Gunnels Wood Road, SG1 2NY, Stevenage, UK. mjs40312@glaxowellcome.co.uk
Baxter
R
R
Bonser
R W
RW
Cockerill
S
S
Gohil
K
K
Parry
N
N
Robinson
E
E
Randall
R
R
Yeates
C
C
Snowden
W
W
Walters
A
A
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*
D000998:Antiviral Agents; D002227:Carbazoles; D007211:Indoles; C089657:arcyriaflavin A; D011493:Protein Kinase C; D015774:Ganciclovir