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 significant...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2010-09, Vol.20 (18), p.5426-5430
Main Authors: Peters, Jens-Uwe, Kühne, Holger, Dehmlow, Henrietta, Grether, Uwe, Conte, Aurelia, Hainzl, Dominik, Hertel, Cornelia, Kratochwil, Nicole A., Otteneder, Michael, Narquizian, Robert, Panousis, Constantinos G., Ricklin, Fabienne, Röver, Stephan
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Flushing
General and cellular metabolism. Vitamins
GPCR
GPR109A
GPR109B
Lead identification
Lipolysis
Medical sciences
Microsomes, Liver - metabolism
Niacin
Niacin - metabolism
Pharmacology. Drug treatments
Pyrido pyrimidinone
Pyrimidinones - administration & dosage
Pyrimidinones - chemistry
Pyrimidinones - metabolism
Pyrimidinones - pharmacology
Rats
Rats, Wistar
Receptors, G-Protein-Coupled - agonists
Receptors, G-Protein-Coupled - metabolism
Receptors, Nicotinic - metabolism
Structure-Activity Relationship
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Summary: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. 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.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2010.07.108