Reduction of peptide character of HIV protease inhibitors that exhibit nanomolar potency against multidrug resistant HIV-1 strains.
Basic Information
ID: ALA1144922
Journal: J Med Chem
Title: Reduction of peptide character of HIV protease inhibitors that exhibit nanomolar potency against multidrug resistant HIV-1 strains.
Authors: Tamamura H, Koh Y, Ueda S, Sasaki Y, Yamasaki T, Aoki M, Maeda K, Watai Y, Arikuni H, Otaka A, Mitsuya H, Fujii N.
Abstract: Novel HIV protease inhibitors containing a hydroxyethylamine dipeptide isostere as a transition state-mimic king structure were synthesized by combining substructures of known HIV protease inhibitors. Among them, TYA5 and TYB5 were proven to be not only potent enzyme inhibitors (K(i) = 0.12 nM and 0.10 nM, respectively) but also strong anti-HIV agents (IC(50) = 9.5 nM and 66 nM, respectively), even against viral strains with multidrug resistance. Furthermore, insertion of an (E)-alkene dipeptide isostere at the P(1)-P(2) position of TYB5 led to development of a purely nonpeptidic protease inhibitor, TYB1 (K(i) = 0.38 nM, IC(50) = 160 nM).
CiteXplore: 12699395
DOI: 10.1021/jm020537i
Patent ID: ┄