Title : ( Design, synthesis and pharmacological evaluation of 6-hydroxy-4-methylquinolin-2(1H)-one derivatives as inotropic agents )
Authors: Hamid Sadeghian , Seyed Mohammad Seyedi , Mohammad Reza Saberi , Reza Shafiee Nick , Azar Hosseini , Mehdi Bakavoli , Seyed Mohammad Taghi Mansouri , Heydar Parsaee ,
Full TextAbstract
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 μM and potent inhibitory activity of PDE3 with IC50 = 0.20 μM.
Keywords
, PDE3 inhibitor, cilostamide, inotropic activity, Rat atria, Isoprenaline, Docking, SAR
@article{paperid:1019662,
author = {Sadeghian, Hamid and Seyedi, Seyed Mohammad and Mohammad Reza Saberi and Reza Shafiee Nick and Azar Hosseini and Bakavoli, Mehdi and Seyed Mohammad Taghi Mansouri and Heydar Parsaee},
title = {Design, synthesis and pharmacological evaluation of 6-hydroxy-4-methylquinolin-2(1H)-one derivatives as inotropic agents},
journal = {Journal of Enzyme Inhibition and Medicinal Chemistry},
year = {2009},
volume = {24},
number = {4},
month = {August},
issn = {1475-6366},
pages = {918--929},
numpages = {11},
keywords = {PDE3 inhibitor; cilostamide; inotropic activity; Rat atria; Isoprenaline; Docking; SAR},
}
%0 Journal Article
%T Design, synthesis and pharmacological evaluation of 6-hydroxy-4-methylquinolin-2(1H)-one derivatives as inotropic agents
%A Sadeghian, Hamid
%A Seyedi, Seyed Mohammad
%A Mohammad Reza Saberi
%A Reza Shafiee Nick
%A Azar Hosseini
%A Bakavoli, Mehdi
%A Seyed Mohammad Taghi Mansouri
%A Heydar Parsaee
%J Journal of Enzyme Inhibition and Medicinal Chemistry
%@ 1475-6366
%D 2009
