Makoto Okita

Synthesis of glucuronides of α,β-unsaturated carboxylic acids

Abstract A practical synthetic method for glucuronides of α,β-unsaturated carboxylic acids is described. An essential point of this method is the use of groups removable using non-reducing conditions for the protection of the glucuronic acid.

Hydroxyindole derivatives as inhibitors of IL-1 generation. I. Synthesis and pharmacological activities of (E)-3-(4-hydroxy-5-methoxyindole-7-yl)-2-methylpropenoic acid derivatives

Summary A series of ( E )-3-(4-hydroxy-5-methoxyindole-7-yl)-2-methylpropenoic acids was prepared and the inhibitory activities of its members on IL-1 generation were evaluated in an in vivo system using the rat carboxymethyl cellulose-lipopolysaccharide (CMC-LPS) air-pouch model. Many compounds in this new series were found to be inhibitors of IL-1 generation. Structure-activity relationships indicated that a methyl substituent at the 1- and 3-positions on the indole ring are important for activity and that a 3,4,5-trimethoxy-substituted 2-phenyl group on the indole ring is suitable to give compounds exhibiting inhibition after oral administration. Among the compounds evaluated, ( E )-3-[1,3-dimethyl-4-hydroxy-5-methoxy-2-(3,4,5-trimethoxyphenyl)indole-7-yl]-2-methylpropenoic acid ( 15m ), which inhibited IL-1 generation by human monocytes stimulated with various reagents such as LPS, opsonized zymosan and immune complexes, showed inhibitory activity in the rat CMC-LPS model after oral administration.