Hydroxyindole derivatives as inhibitors of IL-1 generation. II. Synthesis and pharmacological activities of (E)3-(7-hydroxy-6-methoxyindole-4-yl)-2-methylpropenoic acid derivatives

Article abstract of DOI:10.1016/0223-5234(96)89134-3

A series of (E)-3-(7-hydroxy-6-methoxyindole-4-yl)-2-methylpropenoic acid derivatives was prepared and the inhibitory activities of its members on IL-1 generation were evaluated in an in vitro system using exudate cells from the rat carboxy-methyl cellulose (CMC) induced air-pouch model. All the compounds in this new series were found to be inhibitors of IL-1 generation. In particular, the methoxy-substituted 2-phenyl compounds 28d-f were the most potent inhibitors of IL-1 generation (eg, 28d: IC₅₀ = 0.8 μ,M). The compounds in this series also inhibited IL-1α and IL-1β generations in an in vitro system using human monocytes stimulated with LPS (eg, 28b: IC₅₀ = 1.4 μM (IL-1α) and 0.9 μM (IL-1β)).