Design of Potent and Orally Active GPR119 Agonists for the Treatment of Type II Diabetes.
ACS Med Chem Lett
; 6(8): 936-41, 2015 Aug 13.
Article
em En
| MEDLINE
| ID: mdl-26288697
ABSTRACT
We report herein the design and synthesis of a series of potent and selective GPR119 agonists. Our objective was to develop a GPR119 agonist with properties that were suitable for fixed-dose combination with a DPP4 inhibitor. Starting from a phenoxy analogue (1), medicinal chemistry efforts directed toward reducing half-life and increasing solubility led to the synthesis of a series of benzyloxy analogues. Compound 28 was chosen for further profiling because of its favorable physicochemical properties and excellent GPR119 potency across species. This compound exhibited a clean off-target profile in counterscreens and good in vivo efficacy in mouse oGTT.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
ACS Med Chem Lett
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Estados Unidos