Synthesis and Evaluation of Antituberculosis Activity of Substituted 2,7-Dimethylimidazo [1,2-a]Pyridine-3-Carboxamide Derivatives

Bhagwat Jadhav,Ramesh Yamgar,Y Nivid,R Kenny,Mustapha Mandewale

doi:10.4236/ojmc.2016.64006

Abstract

A series of substituted 2,7-dimethylimidazo[1,2-a]pyridine-3-carboxamides derivatives 5a-5m were synthesized through multi-step reactions. To achieve the synthesis of the desired compounds monobromo and dibromo substituted 2-amino-γ-picoline was reacted with ethyl 2-chloroacetoacetate. The crude ethyl ester subjected to hydrolysis in presence of lithium hydroxide to get 2a and 2b, with imidazo[1,2-a]pyri- dine-3-carboxylic acid to get 3a-3b, on treatment with substituted amines 4a-4g to get desired product 5a-5m in presence of EDCI and HOBt. The substituted imidazo[1,2-a]pyridine-3-carboxamides are characterized by FTIR, 1H-NMR, 13C-NMR and mass spectra. These newly synthesized compounds were tested in vitro for their antimycobacterial activity. The preliminary results of antituberculosis study showed that most of the synthesized compounds 5a-5m demonstrated moderate to good antituberculosis activity. Among the tested compounds 5b, 5d and 5e were found to be the most active with minimum inhibitory concentration (MIC) of 12.5 μg/mL against Mycobacterium tuberculosis (H37 RV strain) ATCC No-27294.

Highlights

The imidazo[1,2-a]pyridines are found to possess various potential biological activities
The preliminary results of antituberculosis study showed that most of the synthesized compounds 5a-5m demonstrated moderate to good antituberculosis activity
Byth and co-workers [8] have synthesized various pyrimidine sulfonamide substituted imidazo[1,2-a]pyridine as cyclindependent kinase (CDK) inhibitors which led to the identification of potent and selective inhibitors of CDK2 and CDK1

Summary

Introduction

The imidazo[1,2-a]pyridines are found to possess various potential biological activities. Byth and co-workers [8] have synthesized various pyrimidine sulfonamide substituted imidazo[1,2-a]pyridine as cyclindependent kinase (CDK) inhibitors which led to the identification of potent and selective inhibitors of CDK2 and CDK1. Ott. and co-worker [11] [12] have synthesized a series of 2,3-substituted imidazo[1,2-a]pyridine derivatives which resemble (3S, 4S)pyrrolidine-N-hydroxy-3-carboxamide and (3R, 4R)pyran-N-hydroxy-3-carboxamide has been reported to have potent selectivity against tumor necrosis factor converting enzyme (TACE). The synthesis and tuberculosis activity of various substituted imidazo[1,2-a]pyridine-3-carboxamides have been reported [13]. Abrahams et al [14] described the synthesis and biological activity of imidazo[1,2-a] pyridine-3-carboxamides against Mycobacterium tuberculosis. Moraski et al synthesized a series of nine 2,7-dimethylimidazo[1,2-a]pyridine-3-car- boxamides and one 2,6-dime-thylimidazo[1,2-a]pyrimidine-3-carboxamide and evaluated for their in vitro antituberculosis activity against replicating, nonreplicating, multi- and extensive drug resistant Mtb strains [15]. Samala G. et al [17] synthesized 2-methylimidazo[1,2-a]-pyridine-3-carboxamides as Mycobacterium tuberculosis Pantothenate synthetase inhibitors

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Conclusion