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 …
G Semple, PJ Skinner, T Gharbaoui… - Journal of medicinal …, 2008 - ACS Publications
G Semple, PJ Skinner, T Gharbaoui, YJ Shin, JK Jung, MC Cherrier, PJ Webb, SY Tamura…
Journal of medicinal chemistry, 2008•ACS PublicationsThe discovery and profiling of 3-(1 H-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.
(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.
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.
ACS Publications