Combination of non-natural D-amino acid derivatives and allophenylnorstatine-dimethylthioproline scaffold in HIV protease inhibitors have high efficac...
Basic Information
ID: ALA1150285
Journal: J Med Chem
Title: Combination of non-natural D-amino acid derivatives and allophenylnorstatine-dimethylthioproline scaffold in HIV protease inhibitors have high efficacy in mutant HIV.
Authors: Nakatani S, Hidaka K, Ami E, Nakahara K, Sato A, Nguyen JT, Hamada Y, Hori Y, Ohnishi N, Nagai A, Kimura T, Hayashi Y, Kiso Y.
Abstract: Several non-natural D-amino acid derivatives were introduced as P2/P3 residues in allophenylnorstatine-containing (Apns; (2S,3S)-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 activities. Interestingly, anti-HIV activity of all the D-amino acid-introduced inhibitors was remarkably enhanced in their anti-HIV activities against a Nelfinavir-resistant clone, which has a D30N mutation in the protease, over that of the wild-type strain. HIV inhibitory activity of several analogues was moderately affected by an inclusion of alpha1-acid glycoprotein in the test medium.
CiteXplore: 18426195
DOI: 10.1021/jm701555p
Patent ID: ┄