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2,4-Diaminopyridine delta-opioid receptor agonists and their associated hERG pharmacology.
- Source :
-
Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2009 Mar 15; Vol. 19 (6), pp. 1702-6. Date of Electronic Publication: 2009 Feb 05. - Publication Year :
- 2009
-
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.
- Subjects :
- 4-Aminopyridine chemical synthesis
4-Aminopyridine pharmacology
Analgesics, Opioid pharmacology
Animals
Cell Line
Combinatorial Chemistry Techniques
Drug Design
ERG1 Potassium Channel
Electromyography methods
Ether-A-Go-Go Potassium Channels metabolism
Humans
Models, Chemical
Rats
Receptors, Opioid, delta chemistry
Structure-Activity Relationship
4-Aminopyridine analogs & derivatives
Chemistry, Pharmaceutical methods
Ether-A-Go-Go Potassium Channels chemistry
Receptors, Opioid, delta agonists
Subjects
Details
- Language :
- English
- ISSN :
- 1464-3405
- Volume :
- 19
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Bioorganic & medicinal chemistry letters
- Publication Type :
- Academic Journal
- Accession number :
- 19231185
- Full Text :
- https://doi.org/10.1016/j.bmcl.2009.01.106