Novel nonopioid non-antiinflammatory analgesics: 3-(aminoalkyl)- and 3-[(4-aryl-1-piperazinyl)alkyl]oxazolo[4,5-b]pyridin-2(3H)-ones

J Med Chem. 1993 Feb 19;36(4):497-503. doi: 10.1021/jm00056a010.

Abstract

A series of 3-(aminoalkyl)- and 3-[(4-aryl-1-piperazinyl)alkyl]oxazolo[4,5-b]pyridin-2(3H)-ones were prepared from their respective oxazolo[4,5-b]pyridin-2(3H)-ones. Several members of this group were found to possess potent analgesic activity in the mouse during a p-phenylquinone writhing induced test. Among them, phenylpiperazine compounds with two-carbon length alkyl chains, 2a and 2b, appeared by high analgesic with little toxicity having neither an antiinflammatory effect nor opioid receptor affinity. The synthesis and structure-affinity relationships for this series are detailed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Analgesics / chemical synthesis*
  • Animals
  • Anti-Inflammatory Agents
  • Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis*
  • Anti-Inflammatory Agents, Non-Steroidal / toxicity
  • Benzoquinones
  • Male
  • Mice
  • Molecular Sequence Data
  • Molecular Structure
  • Oxazoles / chemical synthesis*
  • Oxazoles / toxicity
  • Pain Measurement
  • Pyridones / chemical synthesis*
  • Pyridones / toxicity
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Opioid / metabolism
  • Structure-Activity Relationship

Substances

  • Analgesics
  • Anti-Inflammatory Agents
  • Anti-Inflammatory Agents, Non-Steroidal
  • Benzoquinones
  • Oxazoles
  • Pyridones
  • Receptors, Opioid
  • S 12813
  • 3-(2-(4-(3-(trifluoromethyl)phenyl)-1-piperazinyl)ethyl)oxazolo(4,5-b)pyridin-2(3H)-one
  • phenylbenzoquinone