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ID: ALA1159093
Journal: Bioorg Med Chem Lett
Title: Discovery and optimization of RO-85, a novel drug-like, potent, and selective P2X3 receptor antagonist.
Authors: Brotherton-Pleiss CE, Dillon MP, Ford AP, Gever JR, Carter DS, Gleason SK, Lin CJ, Moore AG, Thompson AW, Villa M, Zhai Y.
Abstract: Despite the extensive literature describing the role of the ATP-gated P2X(3) 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 P2X(3) 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.
CiteXplore: 20045645