Novel P1 chain-extended HIV protease inhibitors possessing potent anti-HIV activity and remarkable inverse antiviral resistance profiles

John F Miller; Michael Brieger; Eric S Furfine; Richard J Hazen; Istvan Kaldor; David Reynolds; Ronald G Sherrill; Andrew Spaltenstein

doi:10.1016/j.bmcl.2005.05.129

Novel P1 chain-extended HIV protease inhibitors possessing potent anti-HIV activity and remarkable inverse antiviral resistance profiles

Bioorg Med Chem Lett. 2005 Aug 1;15(15):3496-500. doi: 10.1016/j.bmcl.2005.05.129.

Authors

John F Miller¹, Michael Brieger, Eric S Furfine, Richard J Hazen, Istvan Kaldor, David Reynolds, Ronald G Sherrill, Andrew Spaltenstein

Affiliation

¹ GlaxoSmithKline, 5 Moore Drive, Research Triangle Park, NC 27709, USA. john.6.miller@gsk.com

PMID: 15990305
DOI: 10.1016/j.bmcl.2005.05.129

Abstract

A novel series of tyrosine-derived HIV protease inhibitors was synthesized and evaluated for in vitro antiviral activity against wild-type virus and two protease inhibitor-resistant viruses. All of the compounds had wild-type antiviral activities that were similar to or greater than several currently marketed HIV protease inhibitors. In addition, a number of compounds in this series were more potent against the drug-resistant mutant viruses than they were against wild-type virus.

MeSH terms

Animals
Anti-HIV Agents / chemical synthesis
Anti-HIV Agents / pharmacology*
Dogs
Drug Resistance, Multiple, Viral / drug effects*
Drug Resistance, Multiple, Viral / genetics
HIV / drug effects*
HIV / genetics
HIV Protease Inhibitors / chemical synthesis
HIV Protease Inhibitors / pharmacology*
Inhibitory Concentration 50
Mutation
Rats
Structure-Activity Relationship
Virus Replication / drug effects*
Virus Replication / genetics

Substances

Anti-HIV Agents
HIV Protease Inhibitors