Synthesis and analgesic activity of hydrochlorides and quaternary ammoniums of epibatidine incorporated with amino acid ester

Bioorg Med Chem Lett. 2003 Dec 15;13(24):4327-9. doi: 10.1016/j.bmcl.2003.09.047.

Abstract

Hydrochloride derivatives 5a-c and quaternary ammonium derivatives 6a-c of epibatidine incorporated with amino acid ester were synthesized and evaluated for their in vivo analgesic activity and toxicity. Among all tested compounds, compound 6c has the most potent analgesic activity. The quaternary ammonium salts 6a and 6c showed better analgesic activity than the corresponding hydrochlorides 5a and 5c. Both 5a-c and 6a-c showed significantly lower toxicity than epibatidine itself.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids
  • Analgesics, Non-Narcotic / chemical synthesis*
  • Analgesics, Non-Narcotic / chemistry
  • Analgesics, Non-Narcotic / pharmacology
  • Animals
  • Bridged Bicyclo Compounds, Heterocyclic / chemical synthesis*
  • Bridged Bicyclo Compounds, Heterocyclic / chemistry
  • Bridged Bicyclo Compounds, Heterocyclic / pharmacology
  • Dose-Response Relationship, Drug
  • Hydrochloric Acid / pharmacology
  • Mice
  • Pain / prevention & control
  • Pyridines / chemical synthesis*
  • Pyridines / chemistry
  • Pyridines / pharmacology
  • Quaternary Ammonium Compounds / chemical synthesis*
  • Quaternary Ammonium Compounds / chemistry
  • Quaternary Ammonium Compounds / pharmacology
  • Structure-Activity Relationship

Substances

  • Amino Acids
  • Analgesics, Non-Narcotic
  • Bridged Bicyclo Compounds, Heterocyclic
  • Pyridines
  • Quaternary Ammonium Compounds
  • epibatidine
  • Hydrochloric Acid