Channelpedia

PubMed 24149495


Referenced in Channelpedia wiki pages of: none

Automatically associated channels: Cav1.2



Title: Synthesis and evaluation of 1,4-dihydropyridine derivatives with calcium channel blocking activity.

Authors: Chris Bladen, Miyase Gözde Gündüz, Rahime Simşek, Cihat Safak, Gerald W Zamponi

Journal, date & volume: Pflugers Arch., 2014 Jul , 466, 1355-63

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/24149495


Abstract
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.