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.
Hilgeroth
Andreas
A
Department of Pharmacy, Martin-Luther-University Halle-Wittenberg, Wolfgang-Langenbeck-Strasse 4, 06120 Halle, Germany. hilgeroth@pharmazie.uni-halle.de
Lilie
Hauke
H
D004095:Dihydropyridines / Q000737:chemistry* / Q000494:pharmacology*; D019281:Dimerization; D004353:Drug Evaluation, Preclinical; D017320:HIV Protease Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology*; D020128:Inhibitory Concentration 50; D013329:Structure-Activity Relationship
D004095:Dihydropyridines; D017320:HIV Protease Inhibitors