Peptidomimetic inhibitors of human immunodeficiency virus protease (HIV-PR): Design, enzyme binding and selectivity, antiviral efficacy, and cell permeability properties

• Published in: Bioorganic & medicinal chemistry letters 1993-05, Vol.3 (5), p.819-824
• Main Authors: Sawyer, T.K., Fisher, J.F., Hester, J.B., Smith, C.W., Tomasselli, A.G., Tarpley, W.G., Burton, P.S., Hui, J.O., McQuade, T.J., Conradi, R.A., Bradford, V.S., Liu, L., Kinner, J.H., Tustin, J., Alexander, D.L., Harrison, A.W., Emmert, D.E., Staples, D.J., Maggiora, L.L., Zhang, Y.Z., Poorman, R.A., Dunna, B.M., Rao, C., Scarborough, P.E., Lowther, W.T., Craik, C., DeCamp, D., Moon, J., Howe, W.J., Heinrikson, R.L.
• Format: Article
• Language: English
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/S0960-894X(00)80673-3

The structure-activity relationships and pharmacophore modeling aspects of a series of HIV PR inhibitors modified at the N- and/or C-terminus of the dipeptide isostere ChaΨ[CH(OH)CH 2]Val (Cha, cyclohexylalanine) are reported. The HIV PR binding affinity-selectivity (vs. human renin, pepsin, and cathepsins-D and E), antiviral efficacy (HIV-1/vVK-1 infected CV-1 cells) and cellular permeabilities (Caco-2) are noted. The structure-activity relationships and pharmacophore modeling aspects of a series of HIV PR inhibitors modified at the N- and/or C-terminus of the dipeptidomimetic ChaΨ[CH(OH)CH 2]Val are reported. HIV PR binding affinity-selectivity (vs. human renin, pepsin, and cathepsins-D and E), antiviral efficacy (HIV-1/vVK-1 infected CV-1 cells), and cellular permeabilities (Caco-2) are noted.