Synthesis of N-[[(substituted-phenyl)carbonyl]amino]-1,2,3,6-tetrahydropyridines with analgesic and hyperglycemic activity.
A group of N-[(phenylcarbonyl)amino]1-2,3,6-tetrahydropyridines, 5, were synthesized to determine the effect that changes in aromatic substitution on the phenyl ring have on analgesic, hyperglycemic, and antiinflammatory activities. All of the N-[(phenylcarbonyl)amino]-1,2,3,6-tetrahydropyridines 5 exhibited potent analgesic activity, relative to morphine, irrespective of the position and physicochemical properties of the aromatic substituent. Pretreatment with naloxone did not alter the analgesic activity of the 4-fluorophenyl derivative 5P. N-[[(2-Fluorophenyl)-carbonyl]amino]-1,2,3,6-tetrahydropyridine (5n) was one of the most active hyperglycemic agents, elevating blood glucose 213 and 127% at 2 and 4 h after a 100 mg/kg po dose. Incorporation of aromatic substituents into the 3 and 4 positions of 1 abolished antiinflammatory activity.
D000700:Analgesics / Q000138:chemical synthesis*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis; D001786:Blood Glucose / Q000378:metabolism; D055598:Chemical Phenomena; D002621:Chemistry; D005260:Female; D007004:Hypoglycemic Agents / Q000138:chemical synthesis*; D008297:Male; D051379:Mice; D011725:Pyridines / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012995:Solubility
D000700:Analgesics; D000893:Anti-Inflammatory Agents; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D011725:Pyridines