Discovery and optimization of RO-85, a novel drug-like, potent, and selective P2X3 receptor antagonist.
Bioorg Med Chem Lett
; 20(3): 1031-6, 2010 Feb 01.
Article
em En
| MEDLINE
| ID: mdl-20045645
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pirazóis
/
Tiofenos
/
Descoberta de Drogas
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Antagonistas do Receptor Purinérgico P2
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article