Document Detail

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.
MedLine Citation:
PMID:  18665582     Owner:  NLM     Status:  MEDLINE    
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.
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 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
Publication Detail:
Type:  Journal Article     Date:  2008-07-30
Journal Detail:
Title:  Journal of medicinal chemistry     Volume:  51     ISSN:  1520-4804     ISO Abbreviation:  J. Med. Chem.     Publication Date:  2008 Aug 
Date Detail:
Created Date:  2008-08-22     Completed Date:  2008-09-10     Revised Date:  2011-11-03    
Medline Journal Info:
Nlm Unique ID:  9716531     Medline TA:  J Med Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  5101-8     Citation Subset:  IM    
Department of Medicinal Chemistry, Arena Pharmaceuticals, 6166 Nancy Ridge Drive, San Diego, California 92121, USA.
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MeSH Terms
Adipocytes / drug effects
Fatty Acids, Nonesterified / blood
Hypolipidemic Agents / chemical synthesis,  pharmacology*,  therapeutic use
Lipolysis / drug effects
Mice, Inbred C57BL
Pyrazoles / chemical synthesis,  pharmacokinetics*
Receptors, G-Protein-Coupled / agonists*
Receptors, Nicotinic
Tetrazoles / chemical synthesis,  pharmacokinetics*
Vasodilation / drug effects
Reg. No./Substance:
0/3-(1H-tetrazol-5-yl)-1,4,5,6-tetrahydrocyclopentapyrazole; 0/Fatty Acids, Nonesterified; 0/HCAR2 protein, human; 0/HCAR3 protein, human; 0/Hypolipidemic Agents; 0/Pyrazoles; 0/Receptors, G-Protein-Coupled; 0/Receptors, Nicotinic; 0/Tetrazoles

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