A facile synthesis and discovery of highly functionalized tetrahydro-pyridines and pyridines as antimycobacterial agents.

Abstract

The four-component reaction of ethyl-3-oxo-4-(arylsulfanyl)butanoate, substituted aromatic aldehydes and ammonium acetate afforded novel ethyl 4-hydroxy-2,6-diaryl-5-(arylsulfanyl)-1,2,5,6-tetrahydro-3-pyridinecarboxylates. These tetrahydro-pyridine esters upon dehydrogenation with dichlorodicyanobenzoquinone (DDQ) afforded highly functionalized pyridines in excellent yields. These novel heterocycles were screened for their in vitro activity against Mycobacterium tuberculosis H37Rv using agar dilution method. Among the compounds screened, ethyl 2,6-di(2-bromophenyl)-4-hydroxy-5-(phenylsulfanyl)-3-pyridinecarboxylate was found to be the most active with a minimum inhibitory concentration of 1.33 microM against Mycobacterium tuberculosis and is 5.74 and 38.17 times more potent than the first line anti-tuberculosis (TB) drugs, ethambutol and pyrazinamide respectively.

• Authors: Suresh Kumar Raju, Michael Rajesh Stephen, Perumal Subbu, Banerjee Debjani, Yogeeswari Perumal, Sriram Dharmarajan
• Journal: Chemical & pharmaceutical bulletin (Chem Pharm Bull (Tokyo)) Vol. 58 Issue 5 Pg. 602-10 (May 2010) ISSN: 1347-5223 [Electronic] Japan
• PMID: 20460783 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Bacterial Agents
• Pyridines
• ethyl 2,6-di(2-bromophenyl)-4-hydroxy-5-(phenylsulfanyl)-3-pyridinecarboxylate
• Pyrazinamide
• Ethambutol

Topics

• Anti-Bacterial Agents (chemical synthesis, chemistry, pharmacology)
• Ethambutol (pharmacology)
• Humans
• Microbial Sensitivity Tests
• Mycobacterium tuberculosis (drug effects)
• Pyrazinamide (pharmacology)
• Pyridines (chemical synthesis, chemistry, pharmacology)