161053-75-4Relevant academic research and scientific papers
A novel nonpeptide HIV-1 protease inhibitor: Elucidation of the binding mode and its application in the design of related analogs
Lunney,Hagen,Domagala,Humblet,Kosinski,Tait,Warmus,Wilson,Ferguson,Hupe,Tummino,Baldwin,Bhat,Liu,Erickson
, p. 2664 - 2677 (2007/10/02)
HIV-1 protease has been identified as a significant target enzyme in AIDS research. While numerous peptide-derived inhibitors have been described, the identification of a nonpeptide inhibitor remains an important goal. Using an HIV-1 protease mass screening technique, 4-hydroxy-3-(3-phenoxypropyl)-2H-1- benzopyran-2-one (1) was identified as a nonpeptide competitive inhibitor of the enzyme. Employing a Monte Carlo-based docking procedure, the coumarin was docked in the active site of the enzyme, revealing a binding mode that was later confirmed by the X-ray crystal analysis. Several analogs were prepared to test the binding interactions and improve the overall binding affinity. The most active compound in the study was 4,7-dihydroxy-3-[4-(2- methoxyphenyl)butyl]-2H-1-benzopyran-2-one (31).
