Anti-inflammatory activity of newly synthesized 2,6-bis-(1,1-dimethylethyl)phenol derivatives

Four new 2,6-bis-(1,1-dimethylethyl)phenol derivatives were synthesized and evaluated for their anti-inflammatory activity, in comparison with indomethacin and vitamin E, using the carrageenan paw oedema assay in rats. Among the tested compounds, the 4-(6,7-dichloro-4H-1,2,4-benzothiadiazine-3-yl)-2,6-bis-(1,1- dimethylethyl)-phenol-S,S-dioxide (4) was the most active compound markedly reducing oedema formation. Moreover compound 4 potentiated, particularly in the early phase of carrageenan paw swelling (2-4 h), the antiphlogistic effect of indomethacin. This compound, on the other hand, did not show ulcerogenic activity at therapeutic doses and did not potentiate the gastric damage induced by high doses of indomethacin. In vitro, the studied compounds (1-4) showed to be moderately active as scavengers of 2,2-diphenyl-1-(2,4,6-trinitrophenyl)hydrazil, 4 being the most active among them. Compound 4, on the contrary, was practically inactive on liposome peroxidation where compounds 1, 2, 3, which are modest anti-inflammatory agents, exerted a good or moderate effect.