1,4-Dihydropyridine derivatives as calcium channel modulators: the role of 3-methoxy-flavone moiety

被引：52

作者：

Budriesi, R ^{[1
]}

Bisi, A ^{[1
]}

Ioan, P ^{[1
]}

Rampa, A ^{[1
]}

Gobbi, S ^{[1
]}

Belluti, F ^{[1
]}

Piazzi, L ^{[1
]}

Valenti, P ^{[1
]}

Chiarini, A ^{[1
]}

机构：

[1] Univ Bologna, Dept Pharmaceut Sci, I-40126 Bologna, Italy

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2005年 / 13卷 / 10期

关键词：

calcium entry blockers; 1,4-dihydropyridine; cardiac selectivity; in vitro assays;

D O I：

10.1016/j.bmc.2005.03.007

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 [生物化学与分子生物学]; 081704 [应用化学];

摘要：

It was earlier recognized that calcium antagonists, and in particular 1,4-dihydropyridines, exhibited distinct cardiovascular profiles. In addition two different splice variants of the L-type calcium channel were found in vascular and cardiac tissues. In this study, novel substituted 1,4-dihydropyridines with a 3-methoxy-flavone moiety were synthesized and structural modifications of the substituents in the dihydropyridine ring of nifedipine were carried out in order to find tissue specific compounds. The negative inotropic, chronotropic and vasorelaxant effects were investigated on guinea-pig left, right atria and aortic strips, respectively. The introduction of an heteroaromatic ring in 4-position of the 1,4-dihydropyridine nucleus led to compounds selective for cardiac tissues. Moreover, different residues in the 1,4-dihydropyridine ring could modulate the chronotropic versus inotropic activity. (c) 2005 Elsevier Ltd. All rights reserved.

引用

页码：3423 / 3430

页数：8

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