Referenced in: none

Automatically associated channels: Kv11.1

Title: 2,4-Diaminopyridine delta-opioid receptor agonists and their associated hERG pharmacology.

Authors: Dafydd R Owen, Margarita Rodriguez-Lens, Martin D Corless, Steven M Gaulier, Valerie A Horne, Ross A Kinloch, Graham N Maw, David W Pearce, Huw Rees, Tracy J Ringer, Thomas Ryckmans, Blanda L C Stammen

Journal, date & volume: Bioorg. Med. Chem. Lett., 2009 Mar 15 , 19, 1702-6

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/19231185

Abstract
A number of libraries were produced to explore the potential of 2,4-diaminopyridine lead 1. The resulting diaminopyridines proved to be potent and selective delta-opioid receptor agonists. Several rounds of lead optimisation using library chemistry identified compound 17 which went on to show efficacy in an electromyography model of neuropathic pain. The structure-activity relationship of the series against the hERG ion channel proved to be a key selectivity hurdle for the series.