3-(1H-Tetrazol-5-yl)-1,4,5,6-tetrahydro-cyclopentapyrazole (MK-0354): A Partial Agonist of the Nicotinic Acid Receptor, G-Protein Coupled Receptor 109a, with Antilipolytic but No Vasodilatory A

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• 作者：Graeme Semple ; Philip J. Skinner ; Tawfik Gharbaoui ; Young-Jun Shin ; Jae-Kyu Jung ; Martin C. Cherrier ; Peter J. Webb ; Susan Y. Tamura ; P. Douglas Boatman ; Carleton R. Sage ; Thomas O. Schrader ; Ruoping
• 刊名：Journal of Medicinal Chemistry
• 出版年：2008
• 出版时间：August 28, 2008
• 年：2008
• 卷：51
• 期：16
• 页码：5101-5108
• 全文大小：184K
• 年卷期：v.51,no.16(August 28, 2008)
• ISSN：1520-4804

文摘

The discovery and profiling of 3-(1H-tetrazol-5-yl)-1,4,5,6-tetrahydro-cyclopentapyrazole (5a, MK-0354), a partial agonist of GPR109a, is described. Compound 5a retained the plasma free fatty acid lowering effects in mice associated with GPR109a agonism, but did not induce vasodilation at the maximum feasible dose. Moreover, preadministration of 5a blocked the flushing effect induced by nicotinic acid but not that induced by PGD₂. This profile made 5a a suitable candidate for further study for the treatment of dyslipidemia.