Combinatorial libraries of HIV and FIV protease inhibitors are characterized
by -keto amide or hydroxyethylamine core structures flanked by on one side
by substituted pyrrolidines, piperidines, or azasugars and on the other side by
phenylalanine, tyrosine, or substituted tyrosines. The libraries are synthesized
via a one step coupling reaction. Highly efficacious drug candidates are identified
by screening the libraries for binding and inhibitory activity against both HIV
and FIV protease. Drug candidates displaying clinically useful activity against
both HIV and FIV protease are identified as being potentially resistive against
a loss of inhibitory activity due to development of resistant strains of HIV.
