Dimeric 4-Aryl-1,4-Dihydropyridines: Development of a Third Class of Nonpeptidic HIV-1 Protease Inhibitors

摘要

Cross-resistance development against most peptidic HIV-1 protease inhibitors (PI) forces thendevelopment of nonpeptidic alternatives. The classes of nonpeptidic protease inhibitors was limited so far toncyclic ureas and 4-hydroxy-2-pyrones with problems of limited bioavailability by extensive metabolism andnprotein binding. Cage dimeric 4-aryl-1,4-dihydropyridines have been developed as third class of nonpeptidic PIs.nIn the following synthesis, molecular modeling and biological activities of a first series of the novel PIs arenreviewed. Bioavailability of the dimers will not be limited by protein binding and metabolism as far as evaluated