Synthesis and antiviral activity of a novel class of HIV-1 protease inhibitors containing a heterocyclic P1′-P2′ amide bond isostere

A novel series of hydroxyethylene-based peptidomimetics that contain 2-substituted nitrogen heterocycles as P1′-P2′ amide bond isosteres has been prepared and evaluated as inhibitors of HIV-1 protease and in vitro HIV-1 replication. Many of these compounds exhibit inhibition constants in the low to subnanomolar range. Structure-activity relationships are discussed.