A knowledge-based, structural-aided discovery of a novel class of 2-phenylimidazo[1, 2-a]pyridine-6-carboxamide H-PGDS inhibitors. (1st September 2021)

• Record Type: Journal Article
• Authors: Schulte, Christie A.; Deaton, David N.; Diaz, Elsie; Do, Young; Gampe, Robert T.; Guss, Jeffrey H.; Hancock, Ashley P.; Hobbs, Heather; Hodgson, Simon T.; Holt, Jason; Jeune, Michael R.; Kahler, Kirsten M.; Kramer, H. Fritz; Le, Joelle; Mortenson, Paul N.; Musetti, Caterina; Nolte, Robert T.; Orband-Miller, Lisa A.; Peckham, Gregory E.; Petrov, Kim G.; Pietrak, Beth L.; Poole, Chuck; Price, Daniel J.; Saxty, Gordon; Shillings, Anthony; Smalley, Terrence L.; Somers, Don O.; Stewart, Eugene L.; Stuart, J. Darren; Thomson, Stephen A.
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 47(2021)
• Publication Date: 2021-09-01
• Subjects: Hematopoietic prostaglandin D2 synthase -- H-PGDS -- PGD2 -- Virtual screen; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2021.128113
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Through an internal virtual screen performed at GlaxoSmithKline a distinct class of 2-phenylimidazo[1, 2-a]pyridine-6-carboxamide H-PGDS inhibitors were discovered. Careful evaluation of crystal structures and SAR led to a novel, potent, and orally active imidazopyridine inhibitor of H-PGDS, 20b . Herein, describes the identification of 2 classes of inhibitors, their syntheses, and their challenges. Abstract: Through an internal virtual screen at GlaxoSmithKline a distinct class of 2-phenylimidazo[1, 2-a]pyridine-6-carboxamide H-PGDS inhibitors were discovered. Careful evaluation of crystal structures and SAR led to a novel, potent, and orally active imidazopyridine inhibitor of H-PGDS, 20b . Herein, describes the identification of 2 classes of inhibitors, their syntheses, and their challenges.