Referenced in: none

Automatically associated channels: Kir2.3

Title: Stereochemical requirements for the mineralocorticoid receptor antagonist activity of dihydropyridines.

Authors: Graciela B Arhancet, Scott S Woodard, Jessica D Dietz, Danny J Garland, Grace M Wagner, Kaliappan Iyanar, Joe T Collins, James R Blinn, Randal E Numann, Xiao Hu, Horng-Chih Huang

Journal, date & volume: J. Med. Chem., 2010 May 27 , 53, 4300-4

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/20408553

Abstract
A number of known 1,4-dihydropyridine CCBs were identified as having comparable potency to the steroidal MR antagonist eplerenone. Chiral resolution of mebudipine revealed that MR and CCB activity reside in opposite enantiomers. Small molecule X-ray crystal structures showed that the C4 stereochemistry of optimized selective MR analogues, e.g. 5, is consistent with MR-active mebudipine. Molecular modeling supports a binding pose consistent with that previously proposed for DHP diesters.