TY - DATA T1 - Reduction of Peptide Character of HIV Protease Inhibitors That Exhibit Nanomolar Potency against Multidrug Resistant HIV-1 Strains PY - 2003/03/18 AU - Hirokazu Tamamura AU - Yasuhiro Koh AU - Satoshi Ueda AU - Yoshikazu Sasaki AU - Tomonori Yamasaki AU - Manabu Aoki AU - Kenji Maeda AU - Yoriko Watai AU - Hisashi Arikuni AU - Akira Otaka AU - Hiroaki Mitsuya AU - Nobutaka Fujii UR - 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 DO - 10.1021/jm020537i.s002 L4 - https://ndownloader.figshare.com/files/5771085 KW - Multidrug Resistant HIV KW - IC 50 KW - TYB 5 KW - nonpeptidic protease inhibitor KW - hydroxyethylamine dipeptide isostere KW - Strains Novel HIV protease inhibitors KW - HIV Protease Inhibitors KW - Exhibit Nanomolar Potency KW - TYA KW - nM KW - K i KW - HIV protease inhibitors N2 - 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). ER -