PubMed 23586669

Referenced in Channelpedia wiki pages of: none

Automatically associated channels: Cav1.2 , Cav1.3

Title: Ligand based approach to L-type calcium channel by imidazo[2,1-b]thiazole-1,4-dihydropyridines: from heart activity to brain affinity.

Authors: Alessandra Locatelli, Sandro Cosconati, Matteo Micucci, Alberto Leoni, Luciana Marinelli, Andrea Bedini, Pierfranco Ioan, Santi Mario Spampinato, Ettore Novellino, Alberto Chiarini, Roberta Budriesi

Journal, date & volume: J. Med. Chem., 2013 May 23 , 56, 3866-77

PubMed link:

The synthesis, characterization, and functional in vitro assay in cardiac and smooth muscle (vascular and nonvascular) of a series of 4-imidazo[2,1-b]thiazole-1,4-dihydropyridines are reported. To define the calcium blocker nature of the imidazo[2,1-b]thiazole-1,4-DHPs and their selectivity on Cav1.2 and Cav1.3 isoforms, we performed binding studies on guinea pig atrial and ventricular membranes on intact cells expressing the cloned Cav1.2a subunit and on rat brain cortex. To get major insights into the reasons for the affinity for Cav1.2 and/or Cav1.3, molecular modeling studies were also undertaken. Some physicochemical and pharmacokinetic properties of selected compounds were calculated and compared. All the biological data collected and reported herein allowed us to rationalize the structure-activity relationship of the 4-imidazo[2,1-b]thiazole-1,4-DHPs and to identify which of these enhanced the activity at the central level.