Development of novel azabenzofuran TRPA1 antagonists as in vivo tools.
Bioorg Med Chem Lett
; 24(15): 3464-8, 2014 Aug 01.
Article
em En
| MEDLINE
| ID: mdl-24953819
ABSTRACT
The transient receptor potential ankyrin 1 (TRPA1) channel is activated by noxious stimuli including chemical irritants and endogenous inflammatory mediators. Antagonists of this channel are currently being investigated for use as therapeutic agents for treating pain, airway disorders, and itch. A novel azabenzofuran series was developed that demonstrated in vitro inhibition of allyl isothiocyanate (AITC)-induced (45)Ca(2+) uptake with nanomolar potencies against both human and rat TRPA1. From this series, compound 10 demonstrated in vivo target coverage in an AITC-induced flinching model in rats while providing unbound plasma concentrations up to 16-fold higher than the TRPA1 rat IC50.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Bloqueadores dos Canais de Cálcio
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Desenho de Fármacos
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Canais de Potencial de Receptor Transitório
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Canais de Cátion TRPC
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Compostos Heterocíclicos com 3 Anéis
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Proteínas do Tecido Nervoso
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Bioorg Med Chem Lett
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2014
Tipo de documento:
Article