Discovery of potent and selective agonists for the free fatty acid receptor 1 (FFA(1)/GPR40), a potential target for the treatment of type II diabetes

A series of 4-phenethynyldihydrocinnamic acid agonists of the free fatty acid receptor 1 (FFA(1)) has been discovered and explored. The preferred compound 20 (TUG-424, EC(50) = 32 nM) significantly increased glucose-stimulated insulin secretion at 100 nM and may serve to explore the role of FFA(1) i...

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Published in:Journal of medicinal chemistry 2008-11, Vol.51 (22), p.7061-7064
Main Authors: Christiansen, Elisabeth, Urban, Christian, Merten, Nicole, Liebscher, Kathrin, Karlsen, Kasper K, Hamacher, Alexandra, Spinrath, Andreas, Bond, Andrew D, Drewke, Christel, Ullrich, Susanne, Kassack, Matthias U, Kostenis, Evi, Ulven, Trond
Format: Article
Language:English
Subjects:
Animals
Cinnamates - chemical synthesis
Cinnamates - chemistry
Cinnamates - pharmacology
Crystallography, X-Ray
Diabetes Mellitus, Type 2 - drug therapy
Dose-Response Relationship, Drug
Drug Discovery
Glucose - antagonists & inhibitors
Glucose - pharmacology
Humans
Insulin - metabolism
Insulin Secretion
Mice
Models, Molecular
Molecular Structure
Rats
Receptors, G-Protein-Coupled - agonists
Stereoisomerism
Structure-Activity Relationship
Time Factors
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Summary:A series of 4-phenethynyldihydrocinnamic acid agonists of the free fatty acid receptor 1 (FFA(1)) has been discovered and explored. The preferred compound 20 (TUG-424, EC(50) = 32 nM) significantly increased glucose-stimulated insulin secretion at 100 nM and may serve to explore the role of FFA(1) in metabolic diseases such as diabetes or obesity.
ISSN:1520-4804
DOI:10.1021/jm8010178