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 μM) and exhibited enzymatic resistance and stability in vitro.