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-1 Pr). Asymmetrical pseudodipeptides, Y-Xaa-gSer-Y (Y = Z, Fmoc; Xaa = Cha, Phe, Tyr, Tic) showed weak inhibitory potency (IC50 > or = 5 mumol/l), whereas the corresponding pseudotripeptides displayed a more significant HIV-1 Pr inhibition: Fmoc-Tic-gSer-Tic-Fmoc (Fmoc = fluorenylmethyloxycarbonyl, Tic = 1,2,3,4-tetradroisoquinoline-3-carboxylic acid) was the most potent compound of the series (IC50 = 385 nmol/l).