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8719357 
Journal Article 
Synthesis and evaluation of 1,4-dihydropyridine derivatives with calcium channel blocking activity 
Bladen, C; Gündüz, MG; Şimşek, R; Şafak, C; Zamponi, GW 
2014 
1 
Pflügers Archiv: European Journal of Physiology
ISSN: 0031-6768
EISSN: 1432-2013 
466 
7 
1355-1363 
English 
24149495 
1,4-Dihydropyridines (DHPs) are an important class of L-type calcium channel blockers that are used to treat conditions such as hypertension and angina. Their primary target in the cardiovascular system is the Cav1.2 L-type calcium channel isoform, however, a number of DHPs also block low-voltage-activated T-type calcium channels. Here, we describe the synthesis of a series of novel DHP derivatives that have a condensed 1,4-DHP ring system (hexahydroquinoline) and report on their abilities to block both L- and T-type calcium channels. Within this series of compounds, modification of a key ester moiety not only regulates the blocking affinity for both L- and T-type channels, but also allows for the development of DHPs with 30-fold selectivity for T-type channels over the L-type. Our data suggest that a condensed dihydropyridine-based scaffold may serve as a pharmacophore for a new class of T-type selective inhibitors. 2013 Springer-Verlag. 
1,4-Dihydropyridine; Aldosterone secretion.; Calcium channels; Cardiovascular; Hypertension