3-Nitro-4-amino benzoic acids and 6-amino nicotinic acids are highly selective agonists of GPR109b.
A series of 3-nitro-4-substituted-aminobenzoic acids were prepared and found to act as potent and highly selective agonists of the orphan human GPCR GPR109b, a low affinity receptor for niacin. No activity was observed at the closely homologous high affinity niacin receptor, GPR109a. A second series, comprising 6-amino-substituted nicotinic acids was, also prepared and several analogues showed comparable activity to the nitroaryl series.
Skinner
Philip J
PJ
Medicinal Chemistry, Arena Pharmaceuticals, 6166 Nancy Ridge Drive, San Diego, CA 92121, USA. pskinner@arenapharm.com
Cherrier
Martin C
MC
Webb
Peter J
PJ
Sage
Carleton R
CR
Dang
Huong T
HT
Pride
Cameron C
CC
Chen
Ruoping
R
Tamura
Susan Y
SY
Richman
Jeremy G
JG
Connolly
Daniel T
DT
Semple
Graeme
G
D000818:Animals; D001565:Benzoates / Q000819:agonists / Q000737:chemistry* / Q000378:metabolism; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D009525:Niacin / Q000378:metabolism; D009539:Nicotinic Acids / Q000819:agonists / Q000737:chemistry* / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000819:agonists* / Q000378:metabolism / Q000502:physiology; D011978:Receptors, Nicotinic / Q000378:metabolism / Q000502:physiology; D013329:Structure-Activity Relationship
D001565:Benzoates; C530636:HCAR2 protein, human; C473653:HCAR3 protein, human; D009539:Nicotinic Acids; D043562:Receptors, G-Protein-Coupled; D011978:Receptors, Nicotinic; D009525:Niacin