Pyrido pyrimidinones as selective agonists of the high affinity niacin receptor GPR109A: optimization of in vitro activity.
Pyrido pyrimidinones are selective agonists of the human high affinity niacin receptor GPR109A (HM74A). They show no activity on the highly homologous low affinity receptor GPR109B (HM74). Starting from a high throughput screening hit the in vitro activity of the pyrido pyrimidinones was significantly improved providing lead compounds suitable for further optimization.
Peters
Jens-Uwe
JU
Pharma Research, F. Hoffmann-La Roche Ltd, 4070 Basel, Switzerland.
Kühne
Holger
H
Dehmlow
Henrietta
H
Grether
Uwe
U
Conte
Aurelia
A
Hainzl
Dominik
D
Hertel
Cornelia
C
Kratochwil
Nicole A
NA
Otteneder
Michael
M
Narquizian
Robert
R
Panousis
Constantinos G
CG
Ricklin
Fabienne
F
Röver
Stephan
S
D000818:Animals; D008862:Microsomes, Liver / Q000378:metabolism; D009525:Niacin / Q000378:metabolism*; D011744:Pyrimidinones / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled / Q000819:agonists* / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000378:metabolism*; D013329:Structure-Activity Relationship
C530636:HCAR2 protein, human; C554445:Hcar2 protein, rat; D011744:Pyrimidinones; D043562:Receptors, G-Protein-Coupled; D011978:Receptors, Nicotinic; D009525:Niacin