Arzneimittelforschung 2008; 58(12): 659-665
DOI: 10.1055/s-0031-1296568
Antiemetics · Gastrointestinal Drugs · Uricosuric Drugs · Urologic Drugs
Editio Cantor Verlag Aulendorf (Germany)

Synthesis of 2-Methyl-4-aryl-4,6,7,8-tetrahydro-5(1H)-quinolone Derivatives and their Effects on Potassium Channels

Gökçe Sevim Öztürk
1  Department of Pharmacology, Faculty of Medicine, Gazi University, Ankara, Turkey
,
Mert Vural
1  Department of Pharmacology, Faculty of Medicine, Gazi University, Ankara, Turkey
,
Miyase Gözde Gündüz
1  Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey
,
Rahime Şimşek
1  Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey
,
Yusuf Sanoğlu
1  Department of Pharmacology, Faculty of Medicine, Gazi University, Ankara, Turkey
,
Cihat Şafak
1  Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey
› Author Affiliations
Further Information

Publication History

Publication Date:
19 December 2011 (online)

Abstract

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 ≥ 3l ≥ 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 ≥3l ≥ 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 ≥ 3l ≥ pinacidil ≥ 3k ≥ 3h ≥ 3a ≥ 3g ≥ 3c ≥ 3i ≥ 3b ≥ 3f.