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.
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.
Mobilio
D
D
Ayerst Laboratories Research Inc., Princeton, New Jersey 08543-8000.
Humber
L G
LG
Katz
A H
AH
Demerson
C A
CA
Hughes
P
P
Brigance
R
R
Conway
K
K
Shah
U
U
Williams
G
G
Labbadia
F
F
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000494:pharmacology; D004487:Edema / Q000517:prevention & control; D066298:In Vitro Techniques; D007210:Indoleacetic Acids / Q000138:chemical synthesis / Q000494:pharmacology; D008297:Male; D011453:Prostaglandins / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007210:Indoleacetic Acids; D011453:Prostaglandins; C056040:pemedolac