Fused bicycles as arylketone bioisosteres leading to potent, orally active thiadiazole H3 antagonists.
Bioorg Med Chem Lett
; 22(9): 3354-7, 2012 May 01.
Article
em En
| MEDLINE
| ID: mdl-22464130
ABSTRACT
A structure-activity relationship study was undertaken to address the lack of oral exposure of the H3 antagonist 1, which incorporated an arylketone. Among a number of sub-series, the 4H-pyrido[1,2-a]pyrimidin-4-one analog 21 showed an improved PK profile in rat and mouse and was active in an obesity model. The pyrimidin-4-one proved to be a novel and useful ketone bioisostere.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Tiadiazóis
/
Antagonistas dos Receptores Histamínicos H3
Limite:
Animals
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article