Synthesis of N-alkyl substituted indolocarbazoles as potent inhibitors of human cytomegalovirus replication

M J Slater; R Baxter; R W Bonser; S Cockerill; K Gohil; N Parry; E Robinson; R Randall; C Yeates; W Snowden; A Walters

doi:10.1016/s0960-894x(01)00352-3

Synthesis of N-alkyl substituted indolocarbazoles as potent inhibitors of human cytomegalovirus replication

Bioorg Med Chem Lett. 2001 Aug 6;11(15):1993-5. doi: 10.1016/s0960-894x(01)00352-3.

Authors

M J Slater¹, R Baxter, R W Bonser, S Cockerill, K Gohil, N Parry, E Robinson, R Randall, C Yeates, W Snowden, A Walters

Affiliation

¹ GlaxoSmithKline Medicines Research Centre, Gunnels Wood Road, SG1 2NY, Stevenage, UK. mjs40312@glaxowellcome.co.uk

PMID: 11454465
DOI: 10.1016/s0960-894x(01)00352-3

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.

MeSH terms

Antiviral Agents / chemical synthesis*
Antiviral Agents / pharmacology*
Carbazoles / chemical synthesis
Carbazoles / pharmacology*
Cells, Cultured
Cytomegalovirus / drug effects*
Drug Resistance / genetics
Drug Resistance / physiology
Ganciclovir / pharmacology
Humans
Indoles / chemical synthesis
Indoles / pharmacology*
Inhibitory Concentration 50
Protein Kinase C / antagonists & inhibitors
Structure-Activity Relationship
Virus Replication / drug effects*

Substances

Antiviral Agents
Carbazoles
Indoles
arcyriaflavin A
Protein Kinase C
Ganciclovir