Nonsteroidal antiinflammatory agents. 2. Synthesis of 4',5-disubstituted 3-biphenylylacetic acids and their derivatives with antiinflammatory and analgesic activities.
A series of 5',5-disubstituted 3-biphenylylacetic acids (5a-n) and several alpha-methyl derivatives (5o-v) were prepared as analogues of a newly developed nonsteroidal antiinflammatory agent, 5'-chloro-5-methoxy-3-biphenylylacetic acid [1 (DKA-9), R = 4-C1Ph; R' = Me], and evaluated for antiinflammatory and analgesic activities using both carrageenan rat paw edema and AcOH writhing assays. Among them, 5-fluoro-3-biphenylylacetic acid (5m) showed the highest antiinflammatory activity, while 2-(3-biphenylyl)propionic acid (5o) showed the highest analgesic activity. However, they were less potent than 1 (R = 4-C1Ph; R' = Me) in these assays.
D000700:Analgesics / Q000138:chemical synthesis*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis*; D001713:Biphenyl Compounds / Q000138:chemical synthesis / Q000494:pharmacology; D055598:Chemical Phenomena; D002621:Chemistry; D007213:Indomethacin / Q000494:pharmacology; D007928:Lethal Dose 50; D008297:Male; D010648:Phenylacetates / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats
D000700:Analgesics; D000893:Anti-Inflammatory Agents; D001713:Biphenyl Compounds; D010648:Phenylacetates; D007213:Indomethacin