Structure-activity relationships among analogues of pemedolac, cis-1-ethyl-1,3,4,9-tetrahydro-4-(phenylmethyl)pyrano[3,4-b]indo le-1-a cetic acid, a potent analgesic agent

J Med Chem. 1988 Nov;31(11):2211-7. doi: 10.1021/jm00119a024.

Abstract

The syntheses of analogues of pemedolac (cis-1-ethyl-1,3,4,9-tetrahydro-4-(phenylmethyl)pyrano[3,4-b]indol e-1-acetic acid), a potent analgesic, are described. They were tested for analgesic and antiinflammatory effects in vivo and for inhibition of prostaglandin production in vitro. Analysis of structure-activity relationships shows that analgesic activity in this series is associated with 1S-cis stereochemistry, the presence of a pi-system (allyl or benzyl) at position 4, and a log P value greater than 4.0.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis*
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Edema / prevention & control
  • In Vitro Techniques
  • Indoleacetic Acids* / chemical synthesis
  • Indoleacetic Acids* / pharmacology
  • Male
  • Prostaglandins / biosynthesis
  • Rats
  • Rats, Inbred Strains
  • Structure-Activity Relationship

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Indoleacetic Acids
  • Prostaglandins
  • pemedolac