Identification of 5H-chromeno[3, 4-c]pyridine and 6H-isochromeno[3, 4-c]pyridine derivatives as potent and selective dual ROCK inhibitors. Issue 21 (1st November 2020)

• Record Type: Journal Article
• Authors: Hu, Zilun; Wang, Cailan; Sitkoff, Doree; Cheadle, Nathan L.; Xu, Songmei; Muckelbauer, Jodi K.; Adam, Leonard P.; Wexler, Ruth R.; Quan, Mimi L.
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 30:Issue 21(2020)
• Publication Date: 2020-11-01
• Subjects: Rho kinase -- ROCK inhibitor -- Chromenopyridine -- Chromenopyrimidine; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2020.127474
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: A novel series of 5 H -chromeno[3, 4- c ]pyridine, 6 H -isochromeno[3, 4- c ]pyridine and 6 H -isochromeno[4, 3- d ]pyrimidine derivatives as dual ROCK1 and ROCK2 inhibitors is described. Optimization led to compounds with sub-nanomolar inhibitory affinity for both kinases and excellent kinome selectivity. Compound 19 exhibited ROCK1 and ROCK2 IC50 of 0.67 nM and 0.18 nM respectively.