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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Published in	Bioorganic & medicinal chemistry letters Vol. 20; no. 18; pp. 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	Journal Article
Language	English
Published	Amsterdam Elsevier Ltd 15.09.2010 Elsevier
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 Flushing Lead identification GPR109A GPR109B GPCR Niacin Lipolysis Pyrido pyrimidinone Nicotinic acid receptor Agonist Ether Nitrogen heterocycle Benzene derivatives Lactam Selectivity In vitro Structure activity relation G protein coupled receptor Bicyclic compound Affinity Fluorine Organic compounds Chemical synthesis
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ISSN	0960-894X 1464-3405 1464-3405
DOI	10.1016/j.bmcl.2010.07.108

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Abstract	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.
AbstractList	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.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. 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.
Author	Hertel, Cornelia Dehmlow, Henrietta Narquizian, Robert Ricklin, Fabienne Kühne, Holger Conte, Aurelia Röver, Stephan Kratochwil, Nicole A. Hainzl, Dominik Panousis, Constantinos G. Grether, Uwe Peters, Jens-Uwe Otteneder, Michael
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Keywords	Flushing Lead identification GPR109A GPR109B GPCR Niacin Lipolysis Pyrido pyrimidinone Nicotinic acid receptor Agonist Ether Nitrogen heterocycle Benzene derivatives Lactam Selectivity In vitro Structure activity relation G protein coupled receptor Bicyclic compound Affinity Fluorine Organic compounds Chemical synthesis
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Snippet	Pyrido pyrimidinones are selective agonists of the human high affinity niacin receptor GPR109A (HM74A). They show no activity on the highly homologous low...
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SubjectTerms	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
Title	Pyrido pyrimidinones as selective agonists of the high affinity niacin receptor GPR109A: Optimization of in vitro activity
URI	https://dx.doi.org/10.1016/j.bmcl.2010.07.108 https://www.ncbi.nlm.nih.gov/pubmed/20724150 https://www.proquest.com/docview/754011039 https://www.proquest.com/docview/954588917
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