%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