Novel arylsulfonamides possessing sub-picomolar HIV protease activities and potent anti-HIV activity against wild-type and drug-resistant viral strains

John F Miller; Eric S Furfine; Mary H Hanlon; Richard J Hazen; John A Ray; Laurence Robinson; Vicente Samano; Andrew Spaltenstein

doi:10.1016/j.bmcl.2003.12.008

Novel arylsulfonamides possessing sub-picomolar HIV protease activities and potent anti-HIV activity against wild-type and drug-resistant viral strains

Bioorg Med Chem Lett. 2004 Feb 23;14(4):959-63. doi: 10.1016/j.bmcl.2003.12.008.

Authors

John F Miller¹, Eric S Furfine, Mary H Hanlon, Richard J Hazen, John A Ray, Laurence Robinson, Vicente Samano, Andrew Spaltenstein

Affiliation

¹ GlaxoSmithKline, 5 Moore Drive, Research Triangle Park, NC 27709, USA. [email protected]

PMID: 15013001
DOI: 10.1016/j.bmcl.2003.12.008

Abstract

A novel series of P1' chain-extended arylsufonamides was synthesized and evaluated for wild-type HIV protease inhibitory activity and in vitro antiviral activity against wild type virus and two protease inhibitor-resistant mutant viruses. All of the compounds showed dramatic increases in enzyme activity as compared to the currently marketed HIV protease inhibitors amprenavir, indinavir, and nelfinavir. In addition, significant improvements in antiviral potencies against wild type and the two mutant viruses were also realized.

MeSH terms

Animals
Anti-HIV Agents / chemical synthesis
Anti-HIV Agents / pharmacology*
Cell Line
Drug Resistance, Multiple, Viral / drug effects
Drug Resistance, Multiple, Viral / genetics*
HIV / drug effects
HIV / genetics*
HIV Protease / drug effects*
HIV Protease / metabolism
HIV Protease Inhibitors / chemical synthesis
HIV Protease Inhibitors / pharmacology*
Humans
Molecular Structure
Mutation
Rats
Structure-Activity Relationship
Sulfonamides / chemical synthesis
Sulfonamides / pharmacology*

Substances

Anti-HIV Agents
HIV Protease Inhibitors
Sulfonamides
HIV Protease