Discovery of a potent, selective, and orally bioavailable acidic 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) inhibitor: discovery of 2-[(3S)-1-[5-(cyclohexylcarbamoyl)-6-propylsulfanylpyridin-2-yl]-3-piperidyl]acetic acid (AZD4017).
J Med Chem
; 55(12): 5951-64, 2012 Jun 28.
Article
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| MEDLINE
| ID: mdl-22691057
ABSTRACT
Inhibition of 11ß-HSD1 is an attractive mechanism for the treatment of obesity and other elements of the metabolic syndrome. We report here the discovery of a nicotinic amide derived carboxylic acid class of inhibitors that has good potency, selectivity, and pharmacokinetic characteristics. Compound 11i (AZD4017) is an effective inhibitor of 11ß-HSD1 in human adipocytes and exhibits good druglike properties and as a consequence was selected for clinical development.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Piperidinas
/
Niacinamida
/
11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 1
/
Inhibidores Enzimáticos
/
Descubrimiento de Drogas
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
J Med Chem
Asunto de la revista:
QUIMICA
Año:
2012
Tipo del documento:
Article
País de afiliación:
Reino Unido