Quinoline and thiazolopyridine allosteric inhibitors of MALT1. Issue 14 (15th July 2019)

• Record Type: Journal Article
• Authors: Scott, David A.; Hatcher, John M.; Liu, Hongyan; Fu, Mingpeng; Du, Guangyan; Fontán, Lorena; Us, Ilkay; Casalena, Gabriella; Qiao, Qi; Wu, Hao; Melnick, Ari; Gray, Nathanael S.
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 29:Issue 14(2019)
• Page Start: 1694
• Page End: 1698
• Publication Date: 2019-07-15
• Subjects: MALT1 -- Protease inhibitors -- Allosteric -- B-cell lymphomas; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2019.05.040
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: Quinolines and thiazolopyridines were developed as allosteric inhibitors of MALT1, with good cellular potency and exquisite selectivity. Mouse pharmacokinetic (PK) profiling showed these to have low in vivo clearance, and moderate oral exposure. The thiazolopyridines were less lipophilic than the quinolines, and one thiazolopyridine example was active in our hIL10 mouse pharmacodynamic (PD) model upon oral dosing.