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

Author: Hilgeroth A.

Source: Mini Reviews in Medicinal Chemistry, Volume 2, Number 3, June 2002 , pp. 235-245(11)

Publisher: Bentham Science Publishers

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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

Language: English

Document Type: Review article

DOI: 10.2174/1389557023406241

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