Synthesis and anti-inflammatory activity of 2,6-di-tert-butylphenols with a heterocyclic group at the 4-position. III.

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Abstract
A series of 2,6-di-tert-butylphenols with azoles at the 4-position was synthesized and evaluated for anti-arthritic activity in adjuvant-induced arthritis (AA) assay. Some compounds were also examined for anti-inflammatory activity in carrageenin-induced rat paw edema assay (CIPE) and for analgesic activity in AcOH[acetic acid]-induced writhing assay in mice. 4-(3,5-Di-tert-butyl-4-hydroxyphenyl)-5-methyl-2-oxo-4-imidazoline (6b) (25 mg/kg, p.o. [orally]) had about the same activity as indomethacin (2 mg/kg, p.o.) in AA assay. Compound 6b (25 mg/kg, p.o.) was as potent as phenylbutazone (50 mg/kg, p.o.) and indomethacin (3 mg/kg, p.o.) in CIPE and showed low acute toxicity (> 1000 mg/kg, mouse, < 400 mg/kg, rat). Compound 6b had radical-scavenging activity in vivo and in vitro, and showed mild inhibitory activity on delayed-type hypersensitivity. 6b is a promising candidate as a new anti-arthritic agents.