Discovery and optimization of N-(3-(1,3-dioxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-4-yloxy)phenyl)benzenesulfonamides as novel GPR119 agonists

Discovery and optimization of N-(3-(1,3-dioxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-4-yloxy)phenyl)benzenesulfonamides as novel GPR119 agonists

The discovery and optimization of novel N-(3-(1,3-dioxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-4-yloxy)phenyl)benzenesulfonamide GPR119 agonists is described. Modification of the pyridylphthalimide motif of the molecule with R(1)=-Me and R(2)=-(i)Pr substituents, incorporated with a 6-fluoro substitut...

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Veröffentlicht in:Bioorganic & medicinal chemistry letters 2014-01, Vol.24 (1), p.156-160
Hauptverfasser: Yu, Ming, Ken Zhang, Jian, Wang, Yingcai, Zhu, Jiang, Kayser, Frank, Medina, Julio C, Siegler, Karen, Conn, Marion, Shan, Bei, Grillo, Mark P, Coward, Peter, Jim Liu, Jiwen
Format: Artikel
Sprache:eng
Schlagworte:
Animals
Dose-Response Relationship, Drug
Drug Discovery
Humans
Microsomes, Liver - chemistry
Microsomes, Liver - metabolism
Molecular Structure
Pyridines - chemistry
Pyridines - metabolism
Pyridines - pharmacology
Rats
Receptors, G-Protein-Coupled - agonists
Structure-Activity Relationship
Sulfonamides - chemistry
Sulfonamides - metabolism
Sulfonamides - pharmacology
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Zusammenfassung:The discovery and optimization of novel N-(3-(1,3-dioxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-4-yloxy)phenyl)benzenesulfonamide GPR119 agonists is described. Modification of the pyridylphthalimide motif of the molecule with R(1)=-Me and R(2)=-(i)Pr substituents, incorporated with a 6-fluoro substitution on the central phenyl ring offered a potent and metabolically stable tool compound 22.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2013.11.053