Synthesis of N-[[(substituted-phenyl)carbonyl]amino]-1,2,3,6-tetrahydropyridines with analgesic and hyperglycemic activity

J Med Chem. 1982 Jun;25(6):720-3. doi: 10.1021/jm00348a021.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics / chemical synthesis*
  • Animals
  • Anti-Inflammatory Agents / chemical synthesis
  • Blood Glucose / metabolism
  • Chemical Phenomena
  • Chemistry
  • Female
  • Hypoglycemic Agents / chemical synthesis*
  • Male
  • Mice
  • Pyridines / chemical synthesis*
  • Pyridines / pharmacology
  • Rats
  • Rats, Inbred Strains
  • Solubility

Substances

  • Analgesics
  • Anti-Inflammatory Agents
  • Blood Glucose
  • Hypoglycemic Agents
  • Pyridines