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Design, synthesis and biological activity of phenoxyacetic acid derivatives as novel free fatty acid receptor 1 agonists.

Abstract：

:The free fatty acid receptor 1 (FFA1) is a novel antidiabetic target for the treatment of type 2 diabetes based on particular mechanism in amplifying glucose-stimulated insulin secretion. We have previously identified a series of phenoxyacetic acid derivatives. Herein, we describe the further chemical modification of this series directed by ligand efficiency and ligand lipophilicity efficiency. All of these efforts lead to the discovery of the promising candidate 16, an excellent FFA1 agonist with robust agonistic activity (43.6 nM), desired LE and LLE values. Moreover, compound 16 revealed a great potential for improving the hyperglycemia levels in both normal and type 2 diabetic mice without the risk of hypoglycemia even at the high dose of 40 mg/kg.

journal_name

Bioorg Med Chem

journal_title

Bioorganic & medicinal chemistry

authors

Li Z,Wang X,Xu X,Yang J,Xia W,Zhou X,Huang W,Qian H

doi

10.1016/j.bmc.2015.10.011

subject

Has Abstract

pub_date

2015-11-15 00:00:00

pages

7158-64

issue

22

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(15)30089-4

journal_volume

23

pub_type

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