Cage DimericN-Acyl- andN-Acyloxy-4-aryl-1,4-dihydropyridines as First Representatives of a Novel Class of HIV-1 Protease Inhibitors

Abstract

The synthesis of a series of novel cage dimeric N-acyl and N-acyloxy-4-aryl-1,4-dihydropyridines starting either from solid-state synthetic ester dimers or from monomeric 4-aryl-1,4-dihydropyridines is presented. Their biological evaluation as novel HIV-1 protease inhibitors showed the most active compounds to be 5c and 5i with inhibitory activities of 52% (50 microM) and 49% (25 microM), respectively. Within each series of N-acyl- and N-acyloxy derivatives NCOBz and NBoc groups were found to be the best substituents. Although they exhibiting only moderate activities these cage dimers hold promise as a class of novel non-peptidic HIV-1 protease inhibitors.