Antimycobacterial activity of spirooxindolo-pyrrolidine, pyrrolizine and pyrrolothiazole hybrids obtained by a three-component regio- and stereoselective 1,3-dipolar cycloaddition

MedChemComm
2011.0

Abstract

Spirooxindolo-pyrrolidine, pyrrolizine and pyrrolothiazole hybrid compounds were obtained in excellent yields from the regio- and stereoselective reaction between β-nitrostyrenes and non-stabilized azomethine ylides, generated in situ from isatin and phenylglycine/proline/thiaproline. These compounds were evaluated for their in vitro activity against Mycobacterium tuberculosis H37Rv (MTB). Eleven compounds were more active than pyrazinamide and one of them, namely 6'-(3-nitrophenyl)-7'-nitro-3',6',7',7a'-tetrahydro-1'H-spiro[indoline-3,5'-pyrrolo[1,2-c]thiazol]-2-one, displayed a 7.6 mM MIC value, which represents a potency similar to that of the first-line anti-TB drug ethambutol and 6.7 times higher than that of pyrazinamide.

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