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Bioorg Med Chem Lett. 2010 Feb 1;20(3):1031-6. doi: 10.1016/j.bmcl.2009.12.044. Epub 2009 Dec 16.

Discovery and optimization of RO-85, a novel drug-like, potent, and selective P2X3 receptor antagonist.

Author information

1
Department of Medicinal Chemistry, Roche Palo Alto, 3431 Hillview Avenue, Palo Alto, CA 94304, USA. brotherton.pleiss@gmail.com

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.

PMID:
20045645
DOI:
10.1016/j.bmcl.2009.12.044
[Indexed for MEDLINE]

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