NONPEPTIDIC HIV PROTEASE INHIBITORS - 3-(S-BENZYL SUBSTITUTED)-4-HYDROXY-6-(PHENYL SUBSTITUTED)-2H-PYRAN-2-ONE WITH AN INVERSE MODE OF BINDING

Authors
PRASAD JVNV PAVLOVSKY A PARA KS ELLSWORTH EL TUMMINO PJ NOUHAN C FERGUSON D
Citation
Jvnv. Prasad et al., NONPEPTIDIC HIV PROTEASE INHIBITORS - 3-(S-BENZYL SUBSTITUTED)-4-HYDROXY-6-(PHENYL SUBSTITUTED)-2H-PYRAN-2-ONE WITH AN INVERSE MODE OF BINDING, Bioorganic & medicinal chemistry letters, 6(10), 1996, pp. 1133-1138
Citations number
19
Categorie Soggetti
Chemistry Inorganic & Nuclear","Chemistry Medicinal
Journal title
Bioorganic & medicinal chemistry letters → ACNP
ISSN journal
0960894X
Volume
6
Issue
10
Year of publication
1996
Pages
1133 - 1138
Database
ISI
SICI code
0960-894X(1996)6:10<1133:NHPI-3>2.0.ZU;2-4
Abstract
Systematic substitutions on 6-phenyl and 3-SCH(2)Ph rings of inhibitor 1, were carried out to optimize the inhibitory activity against HN PR . These studies lead to 3-Sbenzyl esters with enhanced potency. The X- ray crystal structure of 32 bound to HIV PR revealed that the 3-SCH(2) phenyl group is occupying the P-2' pocket, which is contrary to the bi nding mode of 1 (derivative lacking ortho isopropyl ester group). In t he latter case, benzyl group occupies the P-1' pocket. (C) 1996 Elsevi er Science Ltd