Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10591512 | Bioorganic & Medicinal Chemistry Letters | 2013 | 6 Pages |
Abstract
The discovery of a series of 5-HT4 receptor agonists based on a novel 2-alkylbenzimidazole aromatic core is described. Optimization of the 2-substituent of the benzimidazole ring led to a series of agonists with subnanomolar binding affinity and moderate-to-high intrinsic activity relative to that of 5-HT. Consistent with our previously described multivalent design approach to this target, subsequent optimization of the linker and secondary binding group regions of the series afforded compound 18 (TD-8954), a potent and selective 5-HT4 receptor agonist in vitro with demonstrated prokinetic activity in multiple species.
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Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
R. Murray McKinnell, Scott R. Armstrong, David T. Beattie, Paul R. Fatheree, Daniel D. Long, Daniel G. Marquess, Jeng-Pyng Shaw, Ross G. Vickery,