Work

Synthesis and evaluation of imidazole-4,5- and pyrazine-2,3-dicarboxamides targeting dengue and yellow fever virus

Year: 2014

Type: article

Abstract: The results of a high-throughput screening assay using the dengue virus-2 replicon showed that the imidazole 4,5-dicarboxamide (I45DC) derivative (15a) has a high dengue virus inhibitory activity. Based on 15a as a lead compound, a novel class of both disubstituted I45DCs and the resembling pyrazine 2,3-dicarboxamides (P23DCs) were synthesized. Here, we report on their in vitro inhibitory activity against dengue virus (DENV) and yellow fever virus (YFV). Some of these first generation compounds have shown activity against both viruses in the micromolar range. Within this series, compound 15b was observed to display the highest antiviral potency against YFV with an EC50 = 1.85 μM. In addition, compounds 20a and 20b both potently inhibited replication of DENV (EC50 = 0.93 μM) in Vero cells.

Source: European Journal of Medicinal Chemistry

DOI: 10.1016/j.ejmech.2014.09.062

Authors: Milind Saudi, Joanna Zmurko, Suzanne Kaptein, Jef Rozenski, Johan Neyts, Arthur Van Aerschot

Institutions: Rega Institute for Medical Research, KU Leuven

Language: English

Topic: Mosquito-borne diseases and control

Subfield: Public Health, Environmental and Occupational Health

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $4,650