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.
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.
Vara Prasad
J V
JV
Department of Chemistry, Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Company, Ann Arbor, MI 48106, USA.
Boyer
F E
FE
Domagala
J M
JM
Ellsworth
E L
EL
Gajda
C
C
Hagen
S E
SE
Markoski
L J
LJ
Tait
B D
BD
Lunney
E A
EA
Tummino
P J
PJ
Ferguson
D
D
Holler
T
T
Hupe
D
D
Nouhan
C
C
Gracheck
S J
SJ
VanderRoest
S
S
Saunders
J
J
Iyer
K
K
Sinz
M
M
Brodfuehrer
J
J
D000818:Animals; D019380:Anti-HIV Agents / Q000494:pharmacology; D018360:Crystallography, X-Ray; D004285:Dogs; D017320:HIV Protease Inhibitors / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D020128:Inhibitory Concentration 50; D007700:Kinetics; D051379:Mice; D008958:Models, Molecular; D011714:Pyrans / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D013329:Structure-Activity Relationship
D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D011714:Pyrans