Inhibitors of HIV protease: unique non-peptide active site templates.
New templates were designed and prepared which straddle the active site of HIV-1 protease. These templates were designed to be "flexible scaffolds' upon which substituents could be appended to fill the pockets of HIV protease. The new templates prepared and analysed were 4-hydroxy-5H-furan-2-ones, 4-hydroxy-5,6-dihydropyrones, 3-hydroxy-cyclohex-2-enones, and 4-hydroxy-2(1H)-pyridinones, of which the 4-hydroxy-5,6-dihydropyrones were found to be the most potent inhibitors of HIV-1 protease.
Tait
B D
BD
Department of Chemistry, Parke-Davis Pharmaceutical Research Division of the Warner-Lambert Company, Ann Arbor, Michigan 48106, USA.
Domagala
J
J
Ellsworth
E L
EL
Ferguson
D
D
Gajda
C
C
Hupe
D
D
Lunney
E A
EA
Tummino
P J
PJ
D001665:Binding Sites; D015195:Drug Design; D005663:Furans / Q000737:chemistry / Q000378:metabolism; D016333:HIV Protease / Q000378:metabolism*; D017320:HIV Protease Inhibitors / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D008958:Models, Molecular; D011487:Protein Conformation; D011728:Pyridones / Q000737:chemistry / Q000378:metabolism; D011753:Pyrones / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship
D005663:Furans; D017320:HIV Protease Inhibitors; D011728:Pyridones; D011753:Pyrones; D016333:HIV Protease