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).
Department of Pharmaceutical Sciences, University of Ferrara, Italy.
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Marastoni
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Bortolotti
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Salvadori
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R
Tomatis
D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004983:Ethanolamines / Q000737:chemistry / Q000494:pharmacology*; D016333:HIV Protease / Q000378:metabolism*; D017320:HIV Protease Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D006865:Hydrogenation; D018716:Molecular Mimicry; D010455:Peptides / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014269:Trifluoroacetic Acid / Q000494:pharmacology
D004983:Ethanolamines; D017320:HIV Protease Inhibitors; D010455:Peptides; D014269:Trifluoroacetic Acid; D016333:HIV Protease