Combination of Non-natural d-Amino Acid Derivatives and Allophenylnorstatine− Dimethylthioproline Scaffold in HIV Protease Inhibitors Have High Efficacy in Mutant …

S Nakatani, K Hidaka, E Ami, K Nakahara…

Index: Nakatani, Shingo; Hidaka, Koushi; Ami, Ei'Ichi; Nakahara, Koichiro; Sato, Akihiko; Nguyen, Jeffrey-Tri; Hamada, Yoshio; Hori, Yasuko; Ohnishi, Nobuyuki; Nagai, Akinori; Kimura, Tooru; Hayashi, Yoshio; Kiso, Yoshiaki Journal of Medicinal Chemistry, 2008 , vol. 51, # 10 p. 2992 - 3004

Full Text: HTML

Citation Number: 24

Abstract

Several non-natural d-amino acid derivatives were introduced as P2/P3 residues in allophenylnorstatine-containing (Apns;(2 S, 3 S)-3-amino-2-hydroxy-4-phenylbutyric acid) HIV protease inhibitors. The synthetic analogues exhibited potent inhibitory activity against HIV-1 protease enzyme and HIV-1 replication in MT-4 cells. Structure–activity relationships revealed that d-cysteine or serine derivatives contributed to highly potent anti-HIV ...