Discovery of a potent and selective free fatty acid receptor 1 agonist with low lipophilicity and high oral bioavailability
Research output: Contribution to journal › Journal article › Research › peer-review
The free fatty acid receptor 1 (FFA1, also known as GPR40) mediates enhancement of glucose-stimulated insulin secretion and is emerging as a new target for the treatment of type 2 diabetes. Several FFA1 agonists are known, but the majority of these suffer from high lipophilicity. We have previously reported the FFA1 agonist 3 (TUG-424). We here describe the continued structure-activity exploration and optimization of this compound series, leading to the discovery of the more potent agonist 40, a compound with low lipophilicity, excellent in vitro metabolic stability and permeability, complete oral bioavailability, and appreciable efficacy on glucose tolerance in mice.
Original language | English |
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Journal | Journal of Medicinal Chemistry |
Volume | 56 |
Issue number | 3 |
Pages (from-to) | 982-992 |
Number of pages | 11 |
ISSN | 0022-2623 |
DOIs | |
Publication status | Published - 14 Feb 2013 |
Externally published | Yes |
- Administration, Oral, Animals, Biological Availability, Drug Discovery, Magnetic Resonance Spectroscopy, Mice, Models, Molecular, Receptors, G-Protein-Coupled, Spectrometry, Mass, Electrospray Ionization, Structure-Activity Relationship
Research areas
ID: 189162297