Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1372078 | Bioorganic & Medicinal Chemistry Letters | 2010 | 6 Pages |
Despite the extensive literature describing the role of the ATP-gated P2X3 receptors in a variety of physiological processes the potential of antagonists as therapeutic agents has been limited by the lack of drug-like selective molecules. In this paper we report the discovery and optimization of RO-85, a novel drug-like, potent and selective P2X3 antagonist. High-throughput screening of the Roche compound collection identified a small hit series of heterocyclic amides from a large parallel synthesis library. Rapid optimization, facilitated by high-throughput synthesis, focusing on increasing potency and improving drug-likeness resulted in the discovery of RO-85.
Graphical abstractThe discovery and optimization of RO-85, a novel drug-like, potent and selective P2X3 antagonist is described.Figure optionsDownload full-size imageDownload as PowerPoint slide