Studies on the Synthesis and Anti-Inflammatory Activity of 2, 6-Di-tert-butylphenols with a Heterocyclic Group at the 4-Position. II

2, 6-Di-tert-butylphenols with an imidazo [2, 1-b] thiazole or 2, 3-dihydroimidazo [2, 1-b] thiazole group at the 4-position were prepared. Substituents were introduced at the 5-position of 6-(3, 5-ditert-butyl-4-hydroxyphenyl)-2, 3-dihydroimidazo [2, 1-b] thiazole (Ia) by means of the Vilsmeier reaction and Mannich reaction. 6-(3, 5-Di-tert-butyl-4-hydroxyphenyl)-2, 3-dihydroimidazo [2, 1-b] thiazole 1-oxide (IVa) and the 1, 1-dioxide (IVb) were obtained by oxidation of Ia. The above compounds were examined for anti-inflammatory activity in adjuvant-induced arthritis in rats, and some compounds were further tested for activity in the carrageenin-induced rat paw edema assay and in the AcOH-induced writhing assay in mice. Some of the compounds showed potent anti-inflammatory and analgesic activities. The most potent compound, IVa (25 mg/kg, p. o.), had about the same anti-inflammatory activity as indomethacin (2 mg/kg, p. o.), but IVa (50 mg/kg, p. o.) had weaker analgesic activity than aminopyrine (50 mg/kg, p. o.).