SYNTHESIS AND EVALUATION OF -([(2-OXO-1H-QUINOLIN-8-YL)OXY]METHYL)-SUBSTITUTED ALPHA-METHYLIDENE-GAMMA-BUTYROLACTONES

O-Alkylation of 8-hydroxy-1H-quinolin-2-one (1) afforded 8-(2-oxopropo xy)-1H-quinolin-2-one (2) which was immediately cyclized to form the t ricyclic 3-methyl-5H-pyrido[1,2,3-de][1,4]benzoxazine-5-one (3). The R eformatsky-type condensation of 3 furnished antiplatelet ylidene-5-oxo furan-2-yl)methoxy]-1H-quinolin-2-one (4). Its counterparts 7a - f, Ph -substituted at C(2) of the furan ring, were obtained from 1 via alkyl ation and the Reformatsky-type condensation. Although compound 4 was l ess active against platelet aggregation than 7a-f, it was the only com pound which exhibited significant inhibitory activity on high-K+ mediu m, Ca2+-induced vasoconstriction and was more active than most of its Ph-substituted counterparts against norepinephrine-induced vasoconstri ctions.