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.
Redda
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KK
College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee 32307.
Rao
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KN
Heiman
A S
AS
Melles
H
H
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D008297:Male; D051379:Mice; D011725:Pyridines / Q000138:chemical synthesis* / Q000494:pharmacology; D011726:Pyridinium Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011725:Pyridines; D011726:Pyridinium Compounds