3-Phenyl-5-isothiazole carboxamides with potent mGluR1 antagonist activity.
Bioorg Med Chem Lett
; 22(7): 2514-7, 2012 Apr 01.
Article
em En
| MEDLINE
| ID: mdl-22386665
ABSTRACT
The disclosed 3-phenyl-5-isothiazole carboxamides are potent allosteric antagonists of mGluR1 with generally good selectivity relative to the related group 1 receptor mGluR5. Pharmacokinetic properties of a member of this series (1R,2R)-N-(3-(4-methoxyphenyl)-4-methylisothiazol-5-yl)-2-methylcyclopropanecarboxamide (14) are good, showing acceptable plasma and brain exposure after oral dosing. Oral administration of isothiazole 14 gave robust activity in the formalin model of persistent pain which correlated with CNS receptor occupancy.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Dor
/
Tiazóis
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Receptores de Glutamato Metabotrópico
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Antagonistas de Aminoácidos Excitatórios
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Amidas
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Analgésicos
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article