A facile synthesis and antimycobacterial evaluation of novel spiro-pyrido-pyrrolizines and pyrrolidines
An efficient synthesis of 1-methyl-3-[( E)-arylmethylidene]tetrahydro-4(1 H)-pyridinones was achieved by the reaction of 1-methyl-4-piperidone and aromatic aldehydes in the presence of pyrrolidine under solvent-free microwave irradiation. These dipolarophiles upon cycloaddition with nitrile oxide an...
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Published in: | European journal of medicinal chemistry 2009-09, Vol.44 (9), p.3821-3829 |
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Main Authors: | , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | An efficient synthesis of 1-methyl-3-[(
E)-arylmethylidene]tetrahydro-4(1
H)-pyridinones was achieved by the reaction of 1-methyl-4-piperidone and aromatic aldehydes in the presence of pyrrolidine under solvent-free microwave irradiation. These dipolarophiles upon cycloaddition with nitrile oxide and azomethine ylides afford stereoselectively novel spiro-isoxazolines, pyrrolizines and pyrrolidines respectively in excellent yields. The spiro compounds were screened for their
in vitro activity against
Mycobacterium tuberculosis H37Rv (MTB), multi-drug resistant
M. tuberculosis (MDR-TB) and
Mycobacterium smegmatis (MC
2) using agar dilution method. Among the synthesized compounds, 1-methyl-4-(2,4-dichlorophenyl)pyrrolo(spiro[2.3″]oxindole)spiro[3.3′]-1′-methylpiperidin-4′-one was found to be the most active with a minimum inhibitory concentration (MIC) of 1.76 and 0.88
μM against MTB and MDR-TB respectively.
1-Methyl-3-[(
E)-arylmethylidene]tetrahydro-4(1
H)-pyridinones upon cycloaddition with azomethine ylides afford novel spiro-pyrido-pyrrolizines and pyrrolidines in excellent yields stereoselectively. These spiro-heterocycles exhibit promising
in vitro antimycobacterial activity against
Mycobacterium tuberculosis.
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ISSN: | 0223-5234 1768-3254 |
DOI: | 10.1016/j.ejmech.2009.05.010 |