5-N,N-Disubstituted 5-aminopyrazole-3-carboxylic acids are highly potent agonists of GPR109b.
A series of 5-N,N-disubstituted-5-aminopyrazole-3-carboxylic acids were prepared and found to act as highly potent and selective agonists of the G-Protein Coupled Receptor (GPCR) GPR109b, a low affinity receptor for niacin and some aromatic d-amino acids. Little activity was observed at the highly homologous higher affinity niacin receptor, GPR109a.
Skinner
Philip J
PJ
Medicinal Chemistry, Arena Pharmaceuticals, 6166 Nancy Ridge Drive, San Diego, CA, 92121, USA. philip.j.skinner@gmail.com
Webb
Peter J
PJ
Sage
Carleton R
CR
Dang
T Huong
TH
Pride
Cameron C
CC
Chen
Ruoping
R
Tamura
Susan Y
SY
Richman
Jeremy G
JG
Connolly
Daniel T
DT
Semple
Graeme
G
D000818:Animals; D050197:Atherosclerosis / Q000188:drug therapy; D016466:CHO Cells; D002264:Carboxylic Acids / Q000138:chemical synthesis* / Q000494:pharmacology; D002626:Chemistry, Pharmaceutical / Q000379:methods; D006224:Cricetinae; D003412:Cricetulus; D015195:Drug Design; D050171:Dyslipidemias / Q000188:drug therapy; D006801:Humans; D008024:Ligands; D008075:Lipoproteins, HDL / Q000737:chemistry; D008077:Lipoproteins, LDL / Q000737:chemistry; D008956:Models, Chemical; D009525:Niacin / Q000737:chemistry; D011720:Pyrazoles / Q000494:pharmacology; D043562:Receptors, G-Protein-Coupled / Q000819:agonists* / Q000378:metabolism; D011978:Receptors, Nicotinic
D002264:Carboxylic Acids; C473653:HCAR3 protein, human; D008024:Ligands; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D011720:Pyrazoles; D043562:Receptors, G-Protein-Coupled; D011978:Receptors, Nicotinic; D009525:Niacin