Discovery of a potent and selective free fatty acid receptor 1 agonist with low lipophilicity and high oral bioavailability (original) (raw)
Christiansen, E. et al. (2013) Discovery of a potent and selective free fatty acid receptor 1 agonist with low lipophilicity and high oral bioavailability.Journal of Medicinal Chemistry, 56(3), pp. 982-992. (doi: 10.1021/jm301470a)
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Abstract
The free fatty acid receptor 1 (FFA1, also known as GPR40) mediates enhancement of glucosestimulated 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.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Hudson, Dr Brian and Milligan, Professor Graeme |
| Authors: | Christiansen, E., Due-Hansen, M.E., Urban, C., Grundmann, M., Schmidt, J., Hansen, S.V.F., Hudson, B.D., Zaibi, M., Markussen, S.B., Hagesaether, E., Milligan, G., Cawthorne, M.A., Kostenis, E., Kassack, M.U., and Ulven, T. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Molecular Biosciences |
| Journal Name: | Journal of Medicinal Chemistry |
| Publisher: | American Chemical Society |
| ISSN: | 0022-2623 |
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Deposit and Record Details
| ID Code: | 78018 |
|---|---|
| Depositing User: | Mr Stuart Morrison |
| Datestamp: | 15 Apr 2013 07:42 |
| Last Modified: | 28 Sep 2022 14:06 |
| Date of first online publication: | 8 January 2013 |