Derivatives of (phenylsulfonamido-methyl)nicotine and (phenylsulfonamido-methyl)thiazole as novel 11beta-hydroxysteroid dehydrogenase type 1 inhibitors: synthesis and biological activities in vitro.
Acta Pharmacol Sin
; 30(9): 1344-50, 2009 Sep.
Article
en En
| MEDLINE
| ID: mdl-19701236
ABSTRACT
AIM:
To design and synthese a novel class of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) inhibitors, featuring the (phenylsulfonamido-methyl)pyridine and (phenylsulfonamido-methyl)thiazole framework.METHODS:
Our initial lead 4-(phenylsulfonamido-methyl)benzamides were modified. Inhibition of human and mouse 11beta-HSD1 enzymatic activities by the new compounds was determined by a scintillation proximity assay (SPA) using microsomes containing 11beta-HSD1.RESULTS:
Sixteen new compounds (6a-6h, 7a-7h) were designed, synthesized and bioassayed. In dose-response studies, several compounds showed strong inhibitory activities with IC50 values at nanomolar or low nanomolar concentrations. Structure-activity relationships are also discussed with respect to molecular docking results.CONCLUSION:
This study provides two promising new templates for 11beta-HSD1 inhibitors.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 1
/
Nicotina
Límite:
Animals
/
Humans
Idioma:
En
Año:
2009
Tipo del documento:
Article