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2,4-Diaminopyridine d-opioid receptor agonists and their associated hERG pharmacology
journal contribution
posted on 2023-06-08, 20:47 authored by 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 StammenA number of libraries were produced to explore the potential of 2,4-diaminopyridine lead 1. The resulting diaminopyridines proved to be potent and selective d-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.
History
Publication status
- Published
Journal
Bioorganic and Medicinal Chemistry LettersISSN
0960-894XPublisher
ElsevierExternal DOI
Issue
6Volume
19Page range
1702-1706Department affiliated with
- Chemistry Publications
Full text available
- No
Peer reviewed?
- Yes