In vivo optimization of 2,3-diaminopyrazine Rho Kinase inhibitors for the treatment of glaucoma.
Bioorg Med Chem Lett
; 24(8): 1875-9, 2014 Apr 15.
Article
em En
| MEDLINE
| ID: mdl-24684843
ABSTRACT
A series of 2,3,6-pyrazine Rho Kinase inhibitors were optimized for in vivo activity for topical ocular dosing. Modifications of the 2-(piperazin-1-yl)pyrazine derivatives produced compounds with improved solubility and physicochemical properties. Modifications of the 6-pyrazine substituent led to improvements in in vitro potency. Compound 9 had the best in vitro and in vivo potency of EC50=260 nM with a 30% reduction of IOP in a non-human primate model at a dose of 0.33%.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pirazinas
/
Glaucoma
/
Inibidores de Proteínas Quinases
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Quinases Associadas a rho
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article