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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Veröffentlicht in:	Bioorganic & medicinal chemistry letters 2010-09, Vol.20 (18), p.5426-5430
Hauptverfasser:	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:	Artikel
Sprache:	eng
Schlagworte:	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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Zusammenfassung:	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