title: Thieno[2,3-b]pyridines as negative allosteric modulators of metabotropic GluR5 receptors: Lead optimization.
abstract: An HTS campaign of our corporate compound library, and hit-to lead development resulted in thieno[2,3-b]pyridine derivative leads with mGluR5 negative allosteric modulator effects. During the lead optimization process, our objective was to improve affinity and metabolic stability. Modification of the first two targeted regions resulted in compounds with nanomolar affinity, then optimal substitution of the third region improved metabolic stability. One of the most promising compounds showed excellent in vivo efficacy and is a potential development candidate.
authors: Gedeon Richter Plc, Budapest 10, PO Box 27, H-1475, Hungary.
authors: Katalin
authors: K
authors: Nógrádi
authors: Gedeon Richter Plc, Budapest 10, PO Box 27, H-1475, Hungary. Electronic address: gaborwagner75@gmail.com.
authors: Gábor
authors: G
authors: Wágner
authors: Gedeon Richter Plc, Budapest 10, PO Box 27, H-1475, Hungary.
authors: György
authors: G
authors: Domány
authors: Gedeon Richter Plc, Budapest 10, PO Box 27, H-1475, Hungary.
authors: Amrita
authors: A
authors: Bobok
authors: Gedeon Richter Plc, Budapest 10, PO Box 27, H-1475, Hungary.
authors: Ildikó
authors: I
authors: Magdó
authors: Gedeon Richter Plc, Budapest 10, PO Box 27, H-1475, Hungary.
authors: Sándor
authors: S
authors: Kolok
authors: Gedeon Richter Plc, Budapest 10, PO Box 27, H-1475, Hungary.
authors: Mónika L
authors: ML
authors: Mikó-Bakk
authors: Gedeon Richter Plc, Budapest 10, PO Box 27, H-1475, Hungary.
authors: Mónika
authors: M
authors: Vastag
authors: Gedeon Richter Plc, Budapest 10, PO Box 27, H-1475, Hungary.
authors: Katalin
authors: K
authors: Sághy
authors: Gedeon Richter Plc, Budapest 10, PO Box 27, H-1475, Hungary.
authors: István
authors: I
authors: Gyertyán
authors: Gedeon Richter Plc, Budapest 10, PO Box 27, H-1475, Hungary.
authors: János
authors: J
authors: Kóti
authors: Gedeon Richter Plc, Budapest 10, PO Box 27, H-1475, Hungary.
authors: Krisztina
authors: K
authors: Gál
authors: Gedeon Richter Plc, Budapest 10, PO Box 27, H-1475, Hungary.
authors: Sándor
authors: S
authors: Farkas
authors: Gedeon Richter Plc, Budapest 10, PO Box 27, H-1475, Hungary.
authors: György M
authors: GM
authors: Keserű
authors: Gedeon Richter Plc, Budapest 10, PO Box 27, H-1475, Hungary.
authors: István
authors: I
authors: Greiner
authors: Gedeon Richter Plc, Budapest 10, PO Box 27, H-1475, Hungary.
authors: Zsolt
authors: Z
authors: Szombathelyi
mesh_terms: D000494:Allosteric Regulation; D000818:Animals; D057166:High-Throughput Screening Assays; D006801:Humans; D011485:Protein Binding; D011743:Pyrimidines / Q000737:chemistry* / Q000378:metabolism; D051381:Rats; D064529:Receptor, Metabotropic Glutamate 5 / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D011743:Pyrimidines; D064529:Receptor, Metabotropic Glutamate 5; C000601850:thieno(2,3-d)pyrimidine
keywords: Negative allosteric modulator; Thieno[2,3-b]pyridines; mGluR5