HIV protease inhibitors: synthesis and activity of N-aryl-N'-hydroxyalkyl hydrazide pseudopeptides.
We describe the synthesis and activities of a series of pseudopeptides containing an N-aryl-N'-hydroxyalkyl hydrazide core structure to inhibit human immunodeficiency virus protease and viral replication. Of the series, compound Hmb-Leu-N(Bzl)-N(CH2-CH-OH)-rPro-Boc (24) displayed the greatest inhibitory potency (IC50 < 1 microM) and exhibited enzymatic resistance and stability in vitro.
Marastoni
M
M
Department of Pharmaceutical Sciences and Biotechnology Center, University of Ferrara, Via Fossato di Mortara 17-19, I-44100 Ferrara, Italy. mru@dns.unife.it
Baldisserotto
A
A
Trapella
C
C
McDonald
J
J
Bortolotti
F
F
Tomatis
R
R
D015658:HIV Infections / Q000188:drug therapy; D017320:HIV Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D006801:Humans; D006834:Hydrazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D009682:Magnetic Resonance Spectroscopy; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013329:Structure-Activity Relationship; D014779:Virus Replication / Q000187:drug effects
D017320:HIV Protease Inhibitors; D006834:Hydrazines; D010455:Peptides