Oximinoarylsulfonamides as potent HIV protease inhibitors

Clinton M Yeung; Larry L Klein; Charles A Flentge; John T Randolph; Chen Zhao; MingHua Sun; Tatyana Dekhtyar; Vincent S Stoll; Dale J Kempf

doi:10.1016/j.bmcl.2005.03.008

Oximinoarylsulfonamides as potent HIV protease inhibitors

Bioorg Med Chem Lett. 2005 May 2;15(9):2275-8. doi: 10.1016/j.bmcl.2005.03.008.

Authors

Clinton M Yeung¹, Larry L Klein, Charles A Flentge, John T Randolph, Chen Zhao, MingHua Sun, Tatyana Dekhtyar, Vincent S Stoll, Dale J Kempf

Affiliation

¹ Abbott Laboratories, GPRD, D-47D, Building AP52N, 200 Abbott Park Road, Abbott Park, IL 60064-3501, USA. clinton.yeung@abbott.com

PMID: 15837308
DOI: 10.1016/j.bmcl.2005.03.008

Abstract

The need for a potent HIV protease inhibitor (PI) to combat emerging PI-resistant viruses is anticipated. Analogs formulated from the combination of structural fragments of Ritonavir, Lopinavir, and Amprenavir were synthesized. Analogs containing the oxime pharmacophore were found to have improved activities against both wild type and resistant (A17) viruses. The synthesis and structure-activity relationships (SAR) based upon the in vitro IC50 of this series of compounds are reported.

MeSH terms

Binding Sites
Carbamates
Drug Design
Furans
HIV Protease / chemistry
HIV Protease / metabolism
HIV Protease Inhibitors / chemical synthesis*
HIV Protease Inhibitors / chemistry
HIV Protease Inhibitors / pharmacology
Kinetics
Lopinavir
Models, Molecular
Molecular Conformation
Pyrimidinones / chemistry
Ritonavir / chemistry
Sulfonamides / chemical synthesis*
Sulfonamides / chemistry
Sulfonamides / pharmacology*

Substances

Carbamates
Furans
HIV Protease Inhibitors
Pyrimidinones
Sulfonamides
Lopinavir
amprenavir
HIV Protease
Ritonavir