Structure-activity relationships of first bishydroxymethyl-substituted cage dimeric 4-aryl-1,4-dihydropyridines as HIV-1 protease inhibitors

A first series of novel bishydroxymethyl-substituted cage dimeric 4-aryl-1,4-dihydropyridines 5-8 has been synthesised and evaluated as HIV-1 protease and HIV-inhibitors in vitro assays. Moderate activity data of protease inhibition have been found for of the N-Boc substituted compound 8. Reduced activity for compound 6 and almost no residual activity of 5 and 7 emphasise the importance of the tert. butyl substituent for protease inhibitory activity thus supporting a discussed probable binding of the N-acyloxy substituent to the S2/S2' regions of protease. (C) 2003 Editions scientifiques et medicales Elsevier SAS. All rights reserved.