Synthesis of 2-methyl-4-aryl-4,6,7,8-tetrahydro-5(1H)-quinolone derivatives and their effects on potassium channels.

In this study, twelve compounds having 2-methyl-4-aryl-4,6,7,8-tetrahydro-5(1H)-quinolone structure have been synthesized by the reaction of 4-aryl-3-butene-2-on derivatives with 1,3-cyclohexanedione analogs in the presence of ammonium acetate in methanol. The structures of the compounds have been elucidated by IR, 1H-NMR, 13C-NMR, mass spectroscopy and elementel analysis. Their potassium channel opener activities have been investigated on isolated rabbit bladder smooth muscle using pinacidil (CAS 85371-64-8) as standard. The test compounds and pinacidil caused concentration-dependent relaxation responses in bladder smooth muscle strips precontracted with 80 mmol/L KCl with the efficacy order: pinacidil > or = 3g > or = 3j > or = 3a > or = 3l = 3i > or = 3c = 3b > or = 3d > or = 3h > or = 3k. In bladder smooth muscle strips precontracted with 15 mmol/L KCl, the efficacy order was: pinacidil > 3h > or = 3c > or = 3j > or = 3g > or = 3l > or = 3i = 3b > or = 3k > or = 3f > or = 3a. The test compounds and pinacidil caused concentration-dependent inhibition of electrical field stimulation-evoked contractile responses in the bladder smooth muscle strips with the efficacy order: 3j > or = 3l pinacidil > or = 3k > or = 3h > or = 3a > or = 3g > or = 3c > or = 3i > or = 3b > or = 3f.