Design, synthesis and pharmacological evaluation of 6-hydroxy-4-methylquinolin-2(1H)-one derivatives as inotropic agents. Journal of enzyme inhibition and medicinal chemistry [J Enzyme Inhib Med Chem] Journal article | | Title | Design, synthesis and pharmacological evaluation of 6-hydroxy-4-methylquinolin-2(1H)-one derivatives as inotropic agents. | | Author(s) | Sadeghian H, Seyedi SM, Saberi MR, Shafiee Nick R, Hosseini A, Bakavoli M, Taghi Mansouri SM, Parsaee H | | Institution | Department of Chemistry, Faculty of Sciences, Ferdowsi University of Mashhad, Mashhad, I. R. Iran. | | Source | J Enzyme Inhib Med Chem 2009 Apr 8. | | Abstract | Selective PDE3 inhibitors improve cardiac contractility and may be used in congestive heart failure. However, their proarrhythmic potential is the most important side effect. In this research we designed, synthesized and evaluated the potential cardiotonic activity of thirteen PDE3 inhibitors (4-[(4-methyl-2-oxo-1,2-dihydro-6-quinolinyl)oxy]butanamide analogs) using the spontaneously beating atria model. The design strategy was based on the structure of cilostamide, a selective PDE3 inhibitor. In each experiment, atrium of reserpine-treated rat was isolated and the contractile and chronotropic effects of a synthetic compounds were assessed. All experiments were carried out in comparison with IBMX, amrinone and cilostamide as standard compounds. The results showed that, among the new compounds, the best pharmacological profile was obtained with the compound 6-[4-(4-methylpiperazine-1-yl)-4-oxobutoxy]-4-methylquinolin-2(1H)-one, 4j, which displayed selectivity for increasing the force of contraction (165 +/- 4% change over the control) rather than the frequency rate (115 +/- 7% change over the control) at 100 muM and potent inhibitory activity of PDE3 with IC(50) = 0.20 muM. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19555170 |
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