| Abstract: | O-Alkylation of 8-hydroxy-1H-quinolin-2-one ( 1 ) afforded 8-(2-oxopropoxy)-1H-quinolin-2-one ( 2 ) which was immediately cyclized to form the tricyclic 2,3-dihydro-3-hydroxy-3-methyl-5H-pyrido[1,2,3-de][1,4]benzoxazine,-5-one ( 3). The Reformatsky-type condensation of 3 furnished antiplatelet 8-[(2,3,4,5-tetrahydro-2-methyl-4-methylidene-5-oxofuran-2-yl)melhoxy]-1H-quinolin-2-one ( 4 ). Its counterparts 7a – f , Ph-substituted at C(2) of the furan ring, were obtained from 1 via alkylation and the Reformatsky-type condensation. Although compound 4 was less active against platelet aggregation than 7a – f , it was the only compound which exhibited significant inhibitory activity on high-K+ medium, Ca2+-induced vasoconstriction and was more active than most of its Ph-substituted counterparts against norepinephrine-induced vasoconstrictions. |
