期刊
JOURNAL OF MEDICINAL CHEMISTRY
卷 52, 期 24, 页码 7962-7965出版社
AMER CHEMICAL SOC
DOI: 10.1021/jm901434t
关键词
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A series of 3-aryl-4-isoxazolecarboxamides identified from a high-throughput screening campaign as novel, potent small molecule agonists of the human TGR5 G-protein coupled receptor is described. Subsequent optimization resulted in the rapid identification of potent exemplars 6 and 7 which demonstrated improved GLP-1 secretion in vivo via an intracolonic dose coadministered with glucose challenge in a canine model. These novel TGR5 receptor agonists are potentially useful therapeutics for metabolic disorders such as type II diabetes and its associated complications.
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