Lysine sulfonamides as novel HIV-protease inhibitors: Optimization of the Nε-acyl-phenyl spacer

Abstract A series of N α-isobutyl- N α-arylsulfonamido-( N e acyl) lysine and lysinol derivatives were prepared and evaluated as inhibitors of HIV protease and wild type virus. A simple original synthesis was devised to form Nα -(arylsulfonamide)- Nα -isobutyl lysine, which could be easily acylated with carboxylic acids at the Ne position. A two-atom spacer was found to be optimal between this acyl group and a phenyl yielding compounds of sub-nanomolar potency on purified enzyme.