Novel N-substituted benzimidazole CXCR4 antagonists as potential anti-HIV agents

John F Miller; Elizabeth M Turner; Kristjan S Gudmundsson; Stephen Jenkinson; Andrew Spaltenstein; Michael Thomson; Pat Wheelan

doi:10.1016/j.bmcl.2010.02.053

Novel N-substituted benzimidazole CXCR4 antagonists as potential anti-HIV agents

Bioorg Med Chem Lett. 2010 Apr 1;20(7):2125-8. doi: 10.1016/j.bmcl.2010.02.053. Epub 2010 Feb 14.

Authors

John F Miller¹, Elizabeth M Turner, Kristjan S Gudmundsson, Stephen Jenkinson, Andrew Spaltenstein, Michael Thomson, Pat Wheelan

Affiliation

¹ Department of Medicinal Chemistry, Infectious Diseases Center for Excellence in Drug Discovery, GlaxoSmithKline Research and Development, Five Moore Drive, Research Triangle Park, NC 27709-3398, USA. [email protected]

PMID: 20207537
DOI: 10.1016/j.bmcl.2010.02.053

Abstract

The lead optimization of a series of N-substituted benzimidazole CXCR4 antagonists is described. Side chain modifications and stereochemical optimization led to substantial improvements in potency and protein shift to afford compounds with low nanomolar anti-HIV activity.

MeSH terms

Anti-HIV Agents / chemistry*
Anti-HIV Agents / pharmacology*
Benzimidazoles / chemistry*
Benzimidazoles / pharmacology*
Cell Line
HIV Infections / drug therapy*
HIV-1 / drug effects*
Humans
Inhibitory Concentration 50
Receptors, CXCR4 / antagonists & inhibitors*
Receptors, CXCR4 / metabolism

Substances

Anti-HIV Agents
Benzimidazoles
Receptors, CXCR4