Structure-activity relationships of HIV-1 protease inhibitors containing gem-diaminoserine core unit.

Abstract

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).

• Authors: M Marastoni, F Bortolotti, S Salvadori, R Tomatis
• Journal: Arzneimittel-Forschung (Arzneimittelforschung) Vol. 48 Issue 6 Pg. 709-12 (Jun 1998) ISSN: 0004-4172 [Print] Germany
• PMID: 9689433 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Ethanolamines
• HIV Protease Inhibitors
• Peptides
• Trifluoroacetic Acid
• HIV Protease

Topics

• Chemical Phenomena
• Chemistry, Physical
• Ethanolamines (chemistry, pharmacology)
• HIV Protease (metabolism)
• HIV Protease Inhibitors (chemistry, pharmacology)
• Humans
• Hydrogenation
• Molecular Mimicry
• Peptides (chemistry)
• Structure-Activity Relationship
• Trifluoroacetic Acid (pharmacology)