Nonsteroidal antiinflammatory agents. 3. Synthesis of the positional isomers of 4'-chloro-5-methoxy-3-biphenylylacetic acid and their antiinflammatory and analgesic activities.
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.
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004353:Drug Evaluation, Preclinical; D007536:Isomerism; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D010648:Phenylacetates / Q000138:chemical synthesis / Q000494:pharmacology*; D051381:Rats
D000894:Anti-Inflammatory Agents, Non-Steroidal; D010648:Phenylacetates; C006015:DKA 9