Synthetic studies on diuretics. 5-(3,3-N,S-substituted-2-propenoyl)-2,3-dihydro-2- benzo[b]furancarboxylic acids.
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.
Ohsugi
E
E
Fujioka
T
T
Harada
H
H
Nakamura
M
M
Maeda
R
R
D000818:Animals; D002090:Butyrophenones / Q000138:chemical synthesis* / Q000494:pharmacology; D055598:Chemical Phenomena; D002621:Chemistry; D004232:Diuretics / Q000138:chemical synthesis*; D005663:Furans / Q000138:chemical synthesis* / Q000494:pharmacology; D051379:Mice; D009318:Natriuresis / Q000187:drug effects; D011427:Propiophenones / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats
D002090:Butyrophenones; D004232:Diuretics; D005663:Furans; D011427:Propiophenones