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

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.