Budriesi Roberta, Bisi Alessandra, Ioan Pierfranco, Rampa Angela, Gobbi Silvia, Belluti Federica, Piazzi Lorna, Valenti Piero, Chiarini Alberto
Department of Pharmaceutical Sciences, University of Bologna, Via Belmeloro 6, 40126 Bologna, Italy.
Bioorg Med Chem. 2005 May 16;13(10):3423-30. doi: 10.1016/j.bmc.2005.03.007.
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.
人们较早认识到钙拮抗剂，尤其是1,4 - 二氢吡啶类，具有独特的心血管作用特征。此外，在血管和心脏组织中发现了L型钙通道的两种不同剪接变体。在本研究中，合成了具有3 - 甲氧基黄酮部分的新型取代1,4 - 二氢吡啶，并对硝苯地平二氢吡啶环上的取代基进行结构修饰，以寻找组织特异性化合物。分别在豚鼠左、右心房和主动脉条上研究了其负性肌力、负性变时和血管舒张作用。在1,4 - 二氢吡啶核的4 - 位引入杂芳环可得到对心脏组织有选择性的化合物。此外，1,4 - 二氢吡啶环上的不同取代基可调节变时活性与变力活性。
