Dimeric 4-Aryl-1,4-dihydropyridines: development of a third class of nonpeptidic HIV-1 protease inhibitors.
Cross-resistance development against most peptidic HIV-1 protease inhibitors (PI) forces the development of nonpeptidic alternatives. The classes of nonpeptidic protease inhibitors was limited so far to cyclic ureas and 4-hydroxy-2-pyrones with problems of limited bioavailability by extensive metabolism and protein binding. Cage dimeric 4-aryl-1,4-dihydropyridines have been developed as third class of nonpeptidic PIs. In the following synthesis, molecular modeling and biological activities of a first series of the novel PIs are reviewed. Bioavailability of the dimers will not be limited by protein binding and metabolism as far as evaluated.
Hilgeroth
Andreas
A
Department of Pharmacy, Institute of Pharmaceutical Chemistry, Wolfgang-Langenbeck-Str. 4, Halle, D-06120, Germany. hilgeroth@pharmazie.uni-halle.de
D000818:Animals; D001682:Biological Availability; D004095:Dihydropyridines / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D019281:Dimerization; D017320:HIV Protease Inhibitors / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D013329:Structure-Activity Relationship
D004095:Dihydropyridines; D017320:HIV Protease Inhibitors