Nonsteroidal antiinflammatory agents. 3. Synthesis of the positional isomers of 4'-chloro-5-methoxy-3-biphenylylacetic acid and their antiinflammatory and analgesic activities

J Med Chem. 1981 Aug;24(8):1006-10. doi: 10.1021/jm00140a019.

Abstract

The positional isomers 3a-i of 4'-chloro-5-methoxy-3-biphenylylacetic acid [1 (DKA-9), R = 4-ClPh; R' = MeO] which is a newly developed nonsteroidal antiinflammatory agent, have been prepared and evaluated for antiinflammatory and analgesic activities using both the carrageenan-induced rat paw edema and AcOH writhing assays. The 3- and 4-biphenylylacetic acids 3a,d, which closely resemble 1 (R = 4-ClPh, R' = MeO) structurally, showed, by far, excellent activities compared with the other isomers in these assays. However, none of the compounds tested was more active than 1 (R = 4-ClPh; R' = MeO). In this series of compounds, structural requirements for good antiinflammatory activity seemed to be parallel to those for analgesic activity.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal*
  • Drug Evaluation, Preclinical
  • Isomerism
  • Lethal Dose 50
  • Male
  • Mice
  • Phenylacetates / chemical synthesis
  • Phenylacetates / pharmacology*
  • Rats

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Phenylacetates
  • DKA 9