HIV protease inhibitors: synthesis and activity of N-aryl-N'-hydroxyalkyl hydrazide pseudopeptides

M Marastoni; A Baldisserotto; C Trapella; J McDonald; F Bortolotti; R Tomatis

doi:10.1016/j.ejmech.2004.11.016

HIV protease inhibitors: synthesis and activity of N-aryl-N'-hydroxyalkyl hydrazide pseudopeptides

Eur J Med Chem. 2005 May;40(5):445-51. doi: 10.1016/j.ejmech.2004.11.016. Epub 2005 Feb 24.

Authors

M Marastoni¹, A Baldisserotto, C Trapella, J McDonald, F Bortolotti, R Tomatis

Affiliation

¹ Department of Pharmaceutical Sciences and Biotechnology Center, University of Ferrara, Via Fossato di Mortara 17-19, I-44100 Ferrara, Italy. [email protected]

PMID: 15893018
DOI: 10.1016/j.ejmech.2004.11.016

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

HIV Infections / drug therapy
HIV Protease Inhibitors / chemical synthesis*
HIV Protease Inhibitors / chemistry
HIV Protease Inhibitors / pharmacology*
HIV-1 / drug effects*
HIV-1 / enzymology
HIV-1 / physiology
Humans
Hydrazines / chemical synthesis*
Hydrazines / chemistry
Hydrazines / pharmacology
Inhibitory Concentration 50
Magnetic Resonance Spectroscopy
Peptides / chemical synthesis*
Peptides / chemistry
Peptides / pharmacology*
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Structure-Activity Relationship
Virus Replication / drug effects

Substances

HIV Protease Inhibitors
Hydrazines
Peptides