Synthesis and evaluation of novel phenoxypropanolamine derivatives containing acetanilides as potent and selective beta3-adrenergic receptor agonists.
Bioorg Med Chem
; 17(9): 3283-94, 2009 May 01.
Article
em En
| MEDLINE
| ID: mdl-19362005
ABSTRACT
In the search for potent and selective human beta3-adrenergic receptor (AR) agonists as potential drugs for the treatment of obesity and noninsulin-dependent (type II) diabetes, a novel series of phenoxypropanolamine derivatives containing acetanilides were prepared and their biological activities were evaluated at the human beta3-, beta2-, and beta1-ARs. Several of the analogues (21a, 21b, and 27a) exhibited potent agonistic activity at the beta3-AR. Among the compounds described herein, the N-methyl-1-benzylimidazol-2-ylacetanilide derivative (21b) was found to be the most potent and selective beta3-AR agonist, with an EC(50) value of 0.28 microM and no agonistic activity for either the beta1- or beta2-AR. In addition, 21b showed significant hypoglycemic activity in a rodent diabetic model.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fenoxipropanolaminas
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Agonistas de Receptores Adrenérgicos beta 3
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Acetanilidas
Limite:
Animals
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Humans
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Male
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article