Lysine sulfonamides as novel HIV-Protease inhibitors: optimization of the N -acyl-phenyl spacer

A series of Nα-isobutyl-Nα-arylsulfonamido-(N 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 N 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.