Nonsteroidal antiinflammatory agents. 2. Synthesis of 4',5-disubstituted 3-biphenylylacetic acids and their derivatives with antiinflammatory and analgesic activities

J Med Chem. 1981 Jan;24(1):43-7. doi: 10.1021/jm00133a010.

Abstract

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.

MeSH terms

  • Analgesics / chemical synthesis*
  • Animals
  • Anti-Inflammatory Agents / chemical synthesis*
  • Biphenyl Compounds / chemical synthesis
  • Biphenyl Compounds / pharmacology
  • Chemical Phenomena
  • Chemistry
  • Indomethacin / pharmacology
  • Lethal Dose 50
  • Male
  • Phenylacetates / chemical synthesis*
  • Phenylacetates / pharmacology
  • Rats

Substances

  • Analgesics
  • Anti-Inflammatory Agents
  • Biphenyl Compounds
  • Phenylacetates
  • Indomethacin