Nonpeptidic HIV protease inhibitors: 6-alkyl-5,6-dihydropyran-2-ones possessing achiral 3-(4-amino/carboxamide-2-t-butyl,5-methylphenyl thio) moiety: antiviral activities and pharmacokinetic properties

J V Vara Prasad; F E Boyer; J M Domagala; E L Ellsworth; C Gajda; S E Hagen; L J Markoski; B D Tait; E A Lunney; P J Tummino; D Ferguson; T Holler; D Hupe; C Nouhan; S J Gracheck; S VanderRoest; J Saunders; K Iyer; M Sinz; J Brodfuehrer

doi:10.1016/s0960-894x(99)00237-1

Nonpeptidic HIV protease inhibitors: 6-alkyl-5,6-dihydropyran-2-ones possessing achiral 3-(4-amino/carboxamide-2-t-butyl,5-methylphenyl thio) moiety: antiviral activities and pharmacokinetic properties

Bioorg Med Chem Lett. 1999 Jun 7;9(11):1481-6. doi: 10.1016/s0960-894x(99)00237-1.

Affiliation

¹ Department of Chemistry, Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Company, Ann Arbor, MI 48106, USA.

PMID: 10386921
DOI: 10.1016/s0960-894x(99)00237-1

Abstract

Dihydropyran-2-ones possessing amino and carboxamide functionalities on 3-SPh (2-tert-butyl, 5-methyl) ring were synthesized and evaluated for their antiviral activities. Both the enantiomers of inhibitor 15 were synthesized. The in vitro resistance profile, inhibitory activities against cytochrome P450 isozymes and pharmacokinetic properties of inhibitor 15S will be discussed.

MeSH terms

Animals
Anti-HIV Agents / pharmacology
Crystallography, X-Ray
Dogs
HIV Protease Inhibitors / chemical synthesis*
HIV Protease Inhibitors / pharmacokinetics*
Inhibitory Concentration 50
Kinetics
Mice
Models, Molecular
Pyrans / chemical synthesis*
Pyrans / pharmacokinetics*
Structure-Activity Relationship

Substances

Anti-HIV Agents
HIV Protease Inhibitors
Pyrans