%0 Journal Article
%A Tamamura, Hirokazu
%A Koh, Yasuhiro
%A Ueda, Satoshi
%A Sasaki, Yoshikazu
%A Yamasaki, Tomonori
%A Aoki, Manabu
%A Maeda, Kenji
%A Watai, Yoriko
%A Arikuni, Hisashi
%A Otaka, Akira
%A Mitsuya, Hiroaki
%A Fujii, Nobutaka
%D 2003
%T Reduction of Peptide Character of HIV Protease Inhibitors That Exhibit
Nanomolar Potency against Multidrug Resistant HIV-1 Strains
%U https://acs.figshare.com/articles/journal_contribution/Reduction_of_Peptide_Character_of_HIV_Protease_Inhibitors_That_Exhibit_Nanomolar_Potency_against_Multidrug_Resistant_HIV-1_Strains/3681300
%R 10.1021/jm020537i.s002
%2 https://acs.figshare.com/ndownloader/files/5771085
%K Multidrug Resistant HIV
%K IC 50
%K TYB 5
%K nonpeptidic protease inhibitor
%K hydroxyethylamine dipeptide isostere
%K Strains Novel HIV protease inhibitors
%K HIV Protease Inhibitors
%K Exhibit Nanomolar Potency
%K TYA
%K nM
%K K i
%K HIV protease inhibitors
%X 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
(Ki = 0.12 nM and 0.10 nM, respectively) but also strong anti-HIV agents (IC50 = 9.5 nM and
66 nM, respectively), even against viral strains with multidrug resistance. Furthermore,
insertion of an (E)-alkene dipeptide isostere at the P1−P2 position of TYB5 led to development
of a purely nonpeptidic protease inhibitor, TYB1 (Ki = 0.38 nM, IC50 = 160 nM).
%I ACS Publications