1,4-Dihydropyridine derivatives as calcium channel modulators: the role of 3-methoxy-flavone moiety.
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.
Budriesi
Roberta
R
Department of Pharmaceutical Sciences, University of Bologna, Via Belmeloro 6, 40126 Bologna, Italy.
Bisi
Alessandra
A
Ioan
Pierfranco
P
Rampa
Angela
A
Gobbi
Silvia
S
Belluti
Federica
F
Piazzi
Lorna
L
Valenti
Piero
P
Chiarini
Alberto
A
D000818:Animals; D002121:Calcium Channel Blockers / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004095:Dihydropyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D047309:Flavones / Q000737:chemistry*; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology; D014665:Vasodilator Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D047309:Flavones; D014665:Vasodilator Agents; C038806:1,4-dihydropyridine; D009543:Nifedipine