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Mini-Reviews in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1389-5575
ISSN (Online): 1875-5607

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

Author(s): Andreas Hilgeroth

Volume 2, Issue 3, 2002

Page: [235 - 245] Pages: 11

DOI: 10.2174/1389557023406241

Price: $65

Abstract

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.

Keywords: nonpeptide hiv inhibitor, nonpeptide pis, tipranavir


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