Author/Authors :
Philip J. Skinner، نويسنده , , Martin C. Cherrier، نويسنده , , Peter J. Webb، نويسنده , , Young-Jun Shin، نويسنده , , Tawfik Gharbaoui، نويسنده , , Andrew Lindstrom، نويسنده , , Vu Hong Thang، نويسنده , , Susan Y. Tamura، نويسنده , , Huong T. Dang، نويسنده , , Cameron C. Pride، نويسنده , , Ruoping Chen، نويسنده , , Jeremy G. Richman، نويسنده , , Daniel T. Connolly، نويسنده , , Graeme Semple، نويسنده ,
Abstract :
A series of 5-alkyl pyrazole-3-carboxylic acids were prepared and found to act as potent and selective agonists of the human GPCR, GPR109a, the high affinity nicotinic acid receptor. No activity was observed at the highly homologous low affinity niacin receptor, GPR109b. A further series of 4-fluoro-5-alkyl pyrazole-3-carboxylic acids were shown to display similar potency. One example from the series was shown to have improved properties in vivo compared to niacin.
Keywords :
PUMA-G , Niacin , GPR109A , lipolysis , Selectfluor , free fatty acids , GPCRs , Pyrazole carboxylic acids , Cutaneous flushing , HM74 , HM74a , GPR109b
