Studies on 2-Oxoquinoline Derivatives as Blood Platelet Aggregation Inhibitors. IV. Synthesis and Biological Activity of the Metabolites of 6-[4-(1-Cyclohexyl-1H-5-tetrazolyl) butoxy]-2-oxo-1, 2, 3, 4-tetrahydroquinoline (OPC-13013)

Abstract

The metabolites of 6-[4-(1-cyclohexyl-1H-5-tetrazolyl) butoxy]-2-oxo-1, 2, 3, 4-tetrahydroquinoline (OPC-13013) (1), which has a potent inhibitory activity toward blood platelet aggregation and a cerebral vasodilating activity, were synthesized to confirm their structures and to examine their inhibitory activity. The structures of four major metabolites (2a-c and 3) and a specific metabolite (4) found only in man were identified unequivocally by means of comparisons with the synthetic compounds. The inhibitory activity of 3, 4-dehydro-OPC-13013 (3) was about three times higher than that of 1, whereas two metabolites (2a and 2c) had activity almost equal to that of 1.