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 ≥ 3g ≥ 3j ≥ 3a ≥ 31 = 3i ≥ 3c = 3b ≥ 3d ≥ 3h ≥ 3k. In bladder smooth muscle strips precontracted with 15 mmol/L KCl, the efficacy order was: pinacidil > 3h ≥ 3c≥ 3j ≥3g ≥31 ≥ 3i=3b > 3k ≥ 3f ≥ 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 ≥ 31 ≥ pinacidil ≥ 3k ≥ 3h ≥ 3a ≥ 3g > 3e ≥ 3i ≥ 3b ≥ 3f.