- Thieno[2,3-b]pyridines as negative allosteric modulators of metabotropic GluR5 receptors: hit-to-lead optimization.
Thieno[2,3-b]pyridines as negative allosteric modulators of metabotropic GluR5 receptors: hit-to-lead optimization.
Bioorganic & medicinal chemistry letters (2014-07-16)
Katalin Nógrádi, Gábor Wágner, György Domány, Amrita Bobok, Ildikó Magdó, Béla Kiss, Sándor Kolok, Katalin Fónagy, István Gyertyán, Viktor Háda, János Kóti, Krisztina Gál, Sándor Farkas, György M Keserű, István Greiner, Zsolt Szombathelyi
PMID25017030
ABSTRACT
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.
MATERIALS