title: Synthesis of dipeptide-type human immunodeficiency virus (HIV) protease inhibitors with a binding unit to gp120.
abstract: Some dipeptide-type human immunodeficiency virus (HIV) protease inhibitors derived from KNI-102, with a N-carbomethoxycarbonylprolyl-phenylalanine benzyl ester (CPF) moiety as a binding site to gp120, were synthesized. Compounds 11a showed 7--100 times higher HIV protease-inhibitory activity (11a; IC50 = 0.90 microgram/ml, 1.1 microM) than the standard compound 3 or 4 (3; IC50 = 3.7 micrograms/ml, 7.7 microM, 4; IC50 = 75 micrograms/ml, 155 microM). Generally, the compounds substituted at the o-position of the phenoxyacetyl group 7a, 11a, 16a and 21a showed several times higher inhibitory activity than 3.
authors.affiliation: School of Pharmaceutical Sciences, University of Shizuoka, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Asagarasu
authors.forename: N
authors.initials: N
authors.lastname: Takayanagi
authors.forename: K
authors.initials: K
authors.lastname: Achiwa
mesh_terms: D002851:Chromatography, High Pressure Liquid; D015699:HIV Envelope Protein gp120 / Q000378:metabolism*; D017320:HIV Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D009842:Oligopeptides / Q000737:chemistry; D010649:Phenylalanine / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D013055:Spectrophotometry, Infrared
chemical_list: D015699:HIV Envelope Protein gp120; D017320:HIV Protease Inhibitors; D009842:Oligopeptides; C073513:KNI 102; D010649:Phenylalanine