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Please use this identifier to cite or link to this item: http://hdl.handle.net/123456789/6575

Title: Synthesis and antiviral evaluation of 6-(Trifluoromethylbenzyl) and 6-(Fluorobenzyl) analogues of HIV drugs emivirine and GCA-186
Authors: El-Brollosy, Nasser R.
Sorensen, Esben R.
Pedersen, Erik B.
Sanna, Giuseppina
La Colla, Paolo
Loddo, Roberta
Keywords: Alkenyloxymethyluracils
Grignard reaction
HIV-1
Non-nucleoside reverse transcriptase inhibitors
Fluorobenzyl
Analogues of HIV drugs emivirine
Issue Date: 22-Oct-2007
Publisher: Wiley-Vch Verlag Gmbh & Co.
Citation: Archiv der Pharmazie Chemistry in Life Science: 340; 1-11
Abstract: 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 lM), 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 b-keto ester with thiourea or a cross-coupling reaction of 6-chloro-2,4-dimethoxypyrimidines with benzylic Grignard reagents.
Description: Author:2 From the Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
URI: http://hdl.handle.net/123456789/6575
Appears in Collections:College of Pharmacy

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