Synthesis and pharmacological evaluation of some N-[pyridyl(phenyl)carbonylamino]methyl-1,2,3,6-tetrahydropyrid ines.

Reaction of some picolines 5 with 1-chloro-2,4-dinitrobenzene (6) in acetone furnished methyl-substituted 2,4-dinitrophenylpyridinium chlorides 7. Further reaction with phenyl(pyridyl)carbonyl hydrazides 8 at room temperature furnished isolable 2,4-dinitroanilino derivatives 9, which were then refluxed in a water:dioxane mixture (1:4, v/v) to furnish the methyl-substituted phenyl(pyridyl)carbonyl iminopyridinium ylides 10. Reduction of the ylides with NaBH4 finally gave rise to the desired methyl-substituted phenyl(pyridyl)carbonylamino-1,2,3,6-tetrahydropyridines 11. The anti-inflammatory activities of 11a-11l were determined with the carrageenan-soaked sponge model of inflammation in Sprague-Dawley rats, and the analgesic effects of these derivatives were assessed by suppression of acetic acid-induced writhing in male Swiss albino mice. All compounds tested showed moderate to good anti-inflammatory and analgesic effects compared with indomethacin. Compound 11k was the most active analgesic, and 11h was the most effective anti-inflammatory agent among the methyl-substituted tetrahydropyridines.