3-acetyl-5-acylpyridin-2(1H)-ones and 3-acetyl-7,8-dihydro-2,5(1H,6H)-quinolinediones:: synthesis, cardiotonic activity and computational studies

被引：30
|
作者：
Lo Presti, E
Boggia, R
Feltrin, A
Menozzi, G
Dorigo, P
Mosti, L
机构：
[1] Univ Genoa, Dipartimento Sci Farmaceut, I-16132 Genoa, Italy
[2] Univ Genoa, Dipartimento Chim & Tecnol Farmaceut & Alimentari, I-16146 Genoa, Italy
[3] Tecnofarmaci SCPA, I-00040 Rome, Italy
[4] Univ Padua, Dipartimento Farmacol, I-35131 Padua, Italy
来源：
FARMACO | 1999年 / 54卷 / 07期
关键词：
pyridone derivatives; quinolinediones derivatives; inotropic activity; chronotropic activity; molecular electrostatic potentials (MEPs);
D O I：
10.1016/S0014-827X(99)00053-1
中图分类号：
R9 [药学];
学科分类号：
1007 ;
摘要：
A series of milrinone analogues, namely 6-substituted 3-acetyl-5-acylpyridin-2(1H)-ones 4a-c, e, f and 7-substituted or unsubstituted 3-acetyl-7,8-dihydro-2,5(1H,6H)-quinolinediones 4g-j, in which the cyano group was replaced by the acetyl function, was prepared. In a preliminary pharmacological investigation on spontaneously beating atria from reserpine-treated guinea-pigs, all new compounds did not induce any inotropic effect equivalent or higher than that of the milrinone chosen as the reference compound. In order to rationalise how the structure modifications influence the activity and the selectivity of the title compounds, a computational study has been performed. The important role of the substituents in position-3 and -6 on the pyridone nucleus has been highlighted. (C) 1999 Elsevier Science S.A. All rights reserved.
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页码：465 / 474
页数：10
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