Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1369521 | Bioorganic & Medicinal Chemistry Letters | 2016 | 4 Pages |
Abstract
High throughput screening of our corporate compound library followed by hit-to-lead development resulted in a 4-aryl-3-arylsulfonyl-quinoline derivative lead (2) with mGluR5 negative allosteric modulator activity. During the lead optimization process, our objective was to improve affinity and metabolic stability. Modifications at the three targeted regions of the lead structure resulted in compounds with nanomolar affinity and acceptable metabolic stability. One of the most promising compounds (3), showing excellent in vivo efficacy, was selected for preclinical development and subsequent phase I clinical studies.
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Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
János Galambos, György Domány, Katalin Nógrádi, Gábor Wágner, György M. Keserű, Amrita Bobok, Sándor Kolok, Mónika L. Mikó-Bakk, Mónika Vastag, Katalin Sághy, János Kóti, Zoltán Szakács, Zoltán Béni, Krisztina Gál, Zsolt Szombathelyi, István Greiner,