Discovery of novel pyrrole-based scaffold as potent and orally bioavailable free fatty acid receptor 1 agonists for the treatment of type 2 diabetes.
Basic Information
ID: ALA3779832
Journal: Bioorg Med Chem
Title: Discovery of novel pyrrole-based scaffold as potent and orally bioavailable free fatty acid receptor 1 agonists for the treatment of type 2 diabetes.
Authors: Li Z, Pan M, Su X, Dai Y, Fu M, Cai X, Shi W, Huang W, Qian H.
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.
CiteXplore: 27020683
DOI: 10.1016/j.bmc.2016.03.014
Patent ID: ┄