P. Tummino, D. Ferguson, L. Hupe
May 15, 1994
Citations
0
Influential Citations
31
Citations
Quality indicators
Journal
Biochemical and biophysical research communications
Abstract
The nonpeptide compounds C1 (4-hydroxy-3-(3-phenoxypropyl)-1-benzopyran-2-one) and P1 (4-hydroxy-6-phenyl-3-(phenylthio)pyran-2-one) are structurally novel low micromolar inhibitors of the protease of human immunodeficiency virus type 1 (HIV-1). Kinetic analysis revealed that both compounds are competitive inhibitors, with Ki values of 1.0 microM (C1) and 1.1 microM (P1), that act in a reversible fast-binding manner. Structural analogs of both compounds indicate that the pyran-2-one group, the 4-hydroxyl group and substitution at the 3 position are all necessary for inhibitory activity. These two pyranones provide excellent initial compounds in the development of therapeutically effective HIV-1 protease inhibitors, since they are small achiral nonpeptide molecules more easily synthesized and with potentially better pharmacological characteristics than peptide inhibitors of the protease.