title: Synthesis and antimycobacterial activity of highly functionalized tetrahydro-4(1H)-pyridinones.
abstract: A series of 35 2e,3e,6e-triaryltetrahydro-4(1H)-pyridinones, 2e,3e,5e,6e-tetraaryltetrahydro-4(1H)-pyridinones and their N-nitroso and N-cyano analogs have been prepared. All these 35 compounds obtained were screened for their in vitro activity against Mycobacterium tuberculosis H37Rv (MTB). Among them, the N-nitrosopyridinones are found to be more active against MTB than the corresponding N-CN analogs, which, in turn, were slightly more active than NH analogs. In particular, the N-nitroso compounds, 3d, 4b and 4e with halogen-bearing phenyl rings at 2,6-positions showed maximum activity with MIC values of 3.97, 3.11 and 3.11 μM, being more efficacious than the first line anti-TB drugs, ciprofloxacin, ethambutol and pyrazinamide. A general trend has also been discerned in all the three classes of NH, N-CN and N-NO compounds, in each of which those bearing four aryl rings display higher activity than that having three analogously substituted aryl rings disclosing that lipophilicity could be an important factor underlying antimycobacterial activity.
authors.affiliation: Department of Organic Chemistry, School of Chemistry, Madurai Kamaraj University, Madurai 625 021, India.
authors.forename: Velanganni Paul Alex
authors.initials: VP
authors.lastname: Raja
authors.forename: Subbu
authors.initials: S
authors.lastname: Perumal
authors.forename: Perumal
authors.initials: P
authors.lastname: Yogeeswari
authors.forename: Dharmarajan
authors.initials: D
authors.lastname: Sriram
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D011728:Pyridones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D011728:Pyridones