Thieno[2,3-b]pyridines as negative allosteric modulators of metabotropic GluR5 receptors: Hit-to-lead optimization

[Display omitted] An HTS campaign of our corporate compound library resulted in thieno[2,3-b]pyridines derivative hits with mGluR5 negative allosteric modulator effects. During the hit-to-lead development our objective was to improve affinity, and to keep the ligand efficiency values at an acceptabl...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2014-08, Vol.24 (16), p.3845-3849
Main Authors: Nógrádi, Katalin, Wágner, Gábor, Domány, György, Bobok, Amrita, Magdó, Ildikó, Kiss, Béla, Kolok, Sándor, Fónagy, Katalin, Gyertyán, István, Háda, Viktor, Kóti, János, Gál, Krisztina, Farkas, Sándor, Keserű, György M., Greiner, István, Szombathelyi, Zsolt
Format: Article
Language:English
Subjects:
Allosteric Regulation - drug effects
Dose-Response Relationship, Drug
Humans
mGluR5
Molecular Structure
Negative allosteric modulator
Receptor, Metabotropic Glutamate 5 - antagonists & inhibitors
Structure-Activity Relationship
Thienopyridines - chemical synthesis
Thienopyridines - chemistry
Thienopyridines - pharmacology
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Summary:[Display omitted] An HTS campaign of our corporate compound library resulted in thieno[2,3-b]pyridines derivative hits with mGluR5 negative allosteric modulator effects. During the hit-to-lead development our objective was to improve affinity, and to keep the ligand efficiency values at an acceptable level. After different modifications of the linker resulted in a 2-sulfonyl-thieno[2,3-b]pyridines derivative, which fulfilled the lead criteria.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2014.06.057