Discovery of novel pyrrole-based scaffold as potent and orally bioavailable free fatty acid receptor 1 agonists for the treatment of type 2 diabetes.
Bioorg Med Chem
; 24(9): 1981-7, 2016 May 01.
Article
in En
| MEDLINE
| ID: mdl-27020683
ABSTRACT
The free fatty acid receptor 1 (FFA1) has gained significant interest as a novel antidiabetic target. Most of FFA1 agonists reported in the literature bearing a common biphenyl scaffold, which was crucial for toxicity verified by the researchers of Daiichi Sankyo. Herein, we describe the systematic exploration of non-biphenyl scaffold and further chemical modification of the optimal pyrrole scaffold. All of these efforts led to the identification of compound 11 as a potent and orally bioavailable FFA1 agonist without the risk of hypoglycemia. Further molecular modeling studies promoted the understanding of ligand-binding pocket and might help to design more promising FFA1 agonists.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pyrroles
/
Receptors, G-Protein-Coupled
/
Diabetes Mellitus, Type 2
Limits:
Animals
Language:
En
Journal:
Bioorg Med Chem
Journal subject:
BIOQUIMICA
/
QUIMICA
Year:
2016
Document type:
Article