Increased antiviral activity of cyclic urea HIV protease inhibitors by modifying the P1/P1′ substituents

A series of alkyl substituted P1/P1′ analogs was prepared in an attempt to increase translation of the 3-aminoindazole class of HIV protease inhibitors. Increasing the lipophilicity of the P1/P1′ residues dramatically improved translation of enzyme activity to antiviral activity in the whole cell assay. A series of alkyl substituted P1/P1′ analogs was prepared in an attempt to increase translation of the 3-aminoindazole class of HIV protease inhibitors. Increasing the lipophilicity of the P1/P1′ residues dramatically improved translation of enzyme activity to antiviral activity in the whole cell assay.