Synthetic Studies on Diuretics. 5-(3, 3-N, S-Substituted-2-propenoyl)-2, 3-dihydro-2-benzo[b]furancarboxylic Acids

Abstract

6, 7-Dichloro-2, 3-dihydro-2-benzo[b]furancarboxylic acid derivatives having a 3, 3-N, S-disubstituted-2-propenoyl group at the 5-position were prepared by alkylation of 5-(thiocarbamoyl)acetyl derivatives of the 2, 3-dihydro-2-benzo[b]furancarboxylic acid ester or by acetal exchange reaction of 5-[3, 3-bis(alkylthio)-2-propenoyl] derivatives. Synthesis of 5-[4 and/or 5-(di)substituted-4-thiazolin-2-ylidene]acetyl-2, 3-dihydro-2-benzo[b]furancarboxylic acids was also achieved by the reaction of 2-halo-1-methoxyethyl isothiocyanate with the 5-acetyl derivative in the presence of base or through sulfide contraction of 2-[((6, 7-dichloro-2-methoxycarbonyl-2, 3-dihydrobenzo[b]furan-5-yl)carbonyl)methylthio]thiazolium bromide. Some of the compounds which were synthesized showed potent natriuretic activities in rats and mice. The structure-activity relationship is also discussed.