Structure-Guided Discovery of Aminoquinazolines as Brain-Penetrant and Selective LRRK2 Inhibitors

Autor: Mitchell H. Keylor, Anmol Gulati, Solomon D. Kattar, Rebecca E. Johnson, Ryan W. Chau, Kaila A. Margrey, Michael J. Ardolino, Cayetana Zarate, Kelsey E. Poremba, Vladimir Simov, Gregori J. Morriello, John J. Acton, Barbara Pio, Xin Yan, Rachel L. Palte, Spencer E. McMinn, Lisa Nogle, Charles A. Lesburg, Donovon Adpressa, Shishi Lin, Santhosh Neelamkavil, Ping Liu, Jing Su, Laxminarayan G. Hegde, Janice D. Woodhouse, Robert Faltus, Tina Xiong, Paul J. Ciaccio, Jennifer Piesvaux, Karin M. Otte, Harold B. Wood, Matthew E. Kennedy, David Jonathan Bennett, Erin F. DiMauro, Matthew J. Fell, Peter H. Fuller
Rok vydání: 2021
Předmět:
Zdroj: Journal of medicinal chemistry. 65(1)
ISSN: 1520-4804
Popis: The leucine-rich repeat kinase 2 (LRRK2) protein has been genetically and functionally linked to Parkinson's disease (PD), a disabling and progressive neurodegenerative disorder whose current therapies are limited in scope and efficacy. In this report, we describe a rigorous hit-to-lead optimization campaign supported by structural enablement, which culminated in the discovery of brain-penetrant, candidate-quality molecules as represented by compounds
Databáze: OpenAIRE