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...

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Bibliographic Details
Published in:Journal of medicinal chemistry 1981-08, Vol.24 (8), p.1006-1010
Main Authors: Tamura, Yasumitsu, Yoshimoto, Yoshihiko, Tada, Shinichi, Kunimoto, Katsutoshi, Matsumura, Shingo, Murayama, Masao, Shibata, Yoshihisa, Enomoto, Hiroshi
Format: Article
Language:English
Subjects:
Animals
Anti-Inflammatory Agents, Non-Steroidal
Drug Evaluation, Preclinical
Isomerism
Lethal Dose 50
Male
Mice
Phenylacetates - chemical synthesis
Phenylacetates - pharmacology
Rats
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Summary: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.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm00140a019