New structurally simple indolic non peptidic HIV Protease inhibitors were synthesized from (S)-
glycidol by regioselective methods. Following the concept of targeting the protein backbone,
different substitution patterns were introduced onto the common stereodefined
isopropanolamine core modifying the type of functional group on the indole, the position of the
functional group on the indole and the type of the nitrogen containing group (sulfonamides or
perhydroisoquinoline), alternatively. The systematic study on in vitro inhibition activity of such
compounds confirmed the general beneficial effect of the 5-indolyl substituents in presence of
arylsulfonamide moieties, which furnished activities in the micromolar range. Preliminary docking
analysis allowed to identify several key features of the binding mode of such compounds to the
protease.
