title: Syntheses of HIV-protease inhibitors having a peptide moiety which binds to GP120.
abstract: Some HIV-protease inhibitor derivatives having an N-carbomethoxycarbonyl-prolyl-phenylalanine benzyl ester (CPF) moiety as a binding site to gp120 were designed and synthesized. Almost all the compounds bearing CPF on the phenoxyacetyl group showed protease-inhibitory activity. Compounds 25a and 25b, which have the CPF moiety at the ortho- and meta-positions of the phenoxyacetyl group, respectively, had anti-HIV activity, although the others showed only protease-inhibitory activity. These results suggest that 25b binds to gp120 and inhibits HIV protease.
authors.affiliation: School of Pharmaceutical Sciences, University of Shizuoka, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Asagarasu
authors.forename: T
authors.initials: T
authors.lastname: Uchiyama
authors.forename: K
authors.initials: K
authors.lastname: Achiwa
mesh_terms: D001667:Binding, Competitive; D015195:Drug Design; D004926:Escherichia coli / Q000201:enzymology; D015699:HIV Envelope Protein gp120 / Q000737:chemistry*; D017320:HIV Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D015699:HIV Envelope Protein gp120; D017320:HIV Protease Inhibitors; D009842:Oligopeptides; C073513:KNI 102