2. Academic Validation
  3. 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. [email protected]
PMID: 18665582 DOI: 10.1021/jm800258p
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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