1015701-12-8Relevant articles and documents
Synthesis and antiviral evaluation of 6-(trifluoromethylbenzyl) and 6-(fluorobenzyl) analogues of HIV drugs emivirine and GCA-186
El-Brollosy, Nasser R.,Sorensen, Esben R.,Pedersen, Erik B.,Sanna, Giuseppina,La Colla, Paolo,Loddo, Roberta
, p. 9 - 19 (2008/09/21)
The present study describes the synthesis and antiviral evaluation of a series of novel 6-(3-trifluoromethylbenzyl) and 6-(fluorobenzyl) analogues of the HIV drugs emivirine and GCA-186. The objective was to investigate whether the fluoro or trifluoromethyl substituents could lead to an improved antiviral activity against HIV-1 wild type and mutants resistant to non-nucleoside RT inhibitors. The biological test results showed that the most of theses compounds showed good activity against wild type HIV-1. Among them, compound 1-(ethoxymethyl)-6-(3-fluorobenzyl)-5-isopropyluracil (9i) showed the largest inhibitory potency (EC50 = 0.02 μM), resulting equally potent than emivirine against wild type HIV-1. Furthermore, compound 9i showed marginal better activity against resistant mutants than emivirine. The key steps in the synthesis of the target compounds were either reaction of an appropriate β-keto ester with thiourea or a cross-coupling reaction of 6-chloro-2,4-dimethoxypyrimidines with benzylic Grignard reagents.
