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Drug Res (Stuttg) 2016; 66(04): 181-188
DOI: 10.1055/s-0035-1559683
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

Synthesis and Antiviral Evaluation of 1-[(2-Phenoxyethyl)oxymethyl] and 6-(3,5-Dimethoxybenzyl) Analogues of HIV Drugs Emivirine and TNK-651

N. R. El-Brollosy
1   Faculty of Science, Heterocyclic Research Unit, Department of Chemistry, Tanta University, Tanta, Egypt
,
R. Loddo
2   Dipartimento di Scienze Biomediche, Sezione di Microbiologia e Virologia, Università di Cagliari, Cittadella Universitaria, Monserrato (Cagliari), Italy
› Author Affiliations
Further Information

Publication History

received 01 July 2015

accepted 31 July 2015

Publication Date:
27 August 2015 (online)

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Abstract

Novel emivirine analogues 6a, b were synthesized by reacting chloromethyl ethyl ether with 5-ethyl/isopropyl-6-(3,5-dimethoxybenzyl)uracils 5e, f. On the other hand, A series of new TNK-651 analogues 10a–f substituted at N-1 with phenoxyethoxymethyl moiety was prepared on treatment of the corresponding uracils 5a–f with bis(phenoxyethoxy)methane (9). The newly synthesized non-nucleosides were tested for antiviral activity against wild type HIV-1 IIIB as well as the resistant strains N119 (Y181C), A17 (K103N+Y181C), and the triple mutant EFVR (K103R+V179D+P225H) in MT-4 cells. Most of the tested compounds showed good activities. Among them 6-(3,5-dimethylbenzyl)-5-ethyl-1-[(2-phenoxyethyl)oxymethyl]uracil (10c) and 6-(3,5-dimethylbenzyl)-5-isopropyl-1-[(2-phenoxyethyl)oxymethyl]uracil (10d) that showed inhibitory potency higher than emivirine against both wild type HIV-1 and the tested mutant strains, as well as higher activity than efavirenz against EFVR.

Key words

HIV-1 - emivirine - TNK-651 - non-nucleosides - reverse transcriptase inhibitors - uracils
 

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