Nonpeptidic Potent HIV-1 Protease Inhibitors:(4-Hydroxy-6-phenyl-2-oxo-2H-pyran-3-yl) thiomethanes That Span P1-P2'Subsites in a Unique Mode of Binding

…, PJ Tummino, D Ferguson, TJ McQuade…

文献索引：Prasad; Para; Tummino; Ferguson; McQuade; Lunney; Rapundalo; Batley; Hingorani; Domagala; Gracheck; Bhat; Liu; Baldwin; Erickson; Sawyer Journal of Medicinal Chemistry, 1995 , vol. 38, # 6 p. 898 - 905

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被引用次数: 37

摘要

Using molecular modeling and the information derived from the X-ray crystal structure of HIV- 1 protease (HIV PR) complexed with the pyran-2-one 1, a series of (4-hydroxy-6-phenyl-2- oxo-W-pyran-3-yl) thiomethanes was designed and analyzed as novel, nonpeptidic inhibitors of HIV PR. Structure-activity studies led to the discovery of inhibitor 19 having (RS)- 1-(cyclopentylthio)-3-methylbutyl functionalization at the C-3 position, which exhibited a K, ...