STRUCTURE-ACTIVITY-RELATIONSHIPS OF HIV-1 PROTEASE INHIBITORS CONTAINING GEM-DIAMINOSERINE CORE UNIT

Two series of peptidomimetics containing 1,1-diamino-2-hydroxyethane ( gSer) core structure were prepared, from amino acid starting materials , and evaluated as inhibitors of HIV-1 protease (HIV-I Pr). Asymmetric al pseudodipeptides, Y-Xaa-gSer-Y (Y = Z, Fmoc; Xaa = Cha, Phe, Tyr, T ie) showed weak inhibitory potency (IC50 greater than or equal to 5 mu mol/l), whereas the corresponding pseudotripeptides displayed a more significant HIV-1 Pr inhibition: Fmoc-Tic-gSer-Tic-Fmoc (Fmoc = fluore nylmethyloxycarbonyl, Tic = 1,2,3,4-tetradroisoquinoline-3-carboxylic acid) was the most potent compound of the series (IC50 = 385 nmol/l).