Design, Synthesis and Biological Evaluation of 2-(2-Amino-5(6)-nitro-1H-benzimidazol-1-yl)-N-arylacetamides as Antiprotozoal Agents

Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry
Emanuel Hernández-NúñezGabriel Navarrete Vázquez

Abstract

Parasitic diseases are a public health problem affecting millions of people worldwide. One of the scaffolds used in several drugs for the treatment of parasitic diseases is the benzimidazole moiety, a heterocyclic aromatic compound. This compound is a crucial pharmacophore group and is considered a privileged structure in medicinal chemistry. In this study, the benzimidazole core served as a model for the synthesis of a series of 2-(2-amino-5(6)-nitro-1H-benzimidazol-1-yl)-N-arylacetamides 1-8 as benznidazole analogues. The in silico pharmacological results calculated with PASS platform exhibited chemical structures highly similar to known antiprotozoal drugs. Compounds 1-8 when evaluated in silico for acute toxicity by oral dosing, were less toxic than benznidazole. The synthesis of compounds 1-8 were carried out through reaction of 5(6)-nitro-1H-benzimidazol-2-amine (12) with 2-chlroactemides 10a-h, in the presence of K₂CO₃ and acetonitrile as solvent, showing an inseparable mixture of two regioisomers with the -NO₂ group in position 5 or 6 with chemical yields of 60 to 94%. The prediction of the NMR spectra of molecule 1 coincided with the experimental chemical displacements of the regioisomers. Comparisons between the NMR p...Continue Reading

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Citations

Feb 16, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Genaro Rocha-GarduñoGabriel Navarrete-Vázquez

Methods Mentioned

BETA
column chromatography
nuclear magnetic resonance
NMR

Related Concepts

Benzimidazole mononitrate
Amides
Schizonticides
Benzimidazoles
In Vivo NMR Spectroscopy
Drug Modeling
Inhibitory Concentration 50
Helminth Drug Sensitivity Tests
Analogs & derivatives
Antiprotozoal Agents

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