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.
MeSH terms
-
Acids / chemistry*
-
Animals
-
Fatty Acids / metabolism
-
Fluorine / chemistry*
-
Ligands
-
Male
-
Mice
-
Molecular Structure
-
Nicotinic Agonists / chemical synthesis
-
Nicotinic Agonists / chemistry*
-
Nicotinic Agonists / pharmacology*
-
Pyrazoles / chemical synthesis
-
Pyrazoles / chemistry*
-
Pyrazoles / pharmacology*
-
Rats
-
Receptors, G-Protein-Coupled / agonists*
-
Receptors, G-Protein-Coupled / metabolism
-
Receptors, Nicotinic / metabolism
-
Structure-Activity Relationship
Substances
-
Acids
-
Fatty Acids
-
Ligands
-
Nicotinic Agonists
-
Pyrazoles
-
Receptors, G-Protein-Coupled
-
Receptors, Nicotinic
-
Fluorine
-
pyrazole