1. Academic Validation
  2. 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 activity in mice

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 activity in mice

  • J Med Chem. 2008 Aug 28;51(16):5101-8. doi: 10.1021/jm800258p.
Graeme Semple 1 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 Chen Steven L Colletti James R Tata M Gerard Waters Kang Cheng Andrew K Taggart Tian-Quan Cai Ester Carballo-Jane Dominic P Behan Daniel T Connolly Jeremy G Richman
Affiliations

Affiliation

  • 1 Department of Medicinal Chemistry, Arena Pharmaceuticals, 6166 Nancy Ridge Drive, San Diego, California 92121, USA. gsemple@arenapharm.com
Abstract

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.

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