Structure guided design of a series of selective pyrrolopyrimidinone MARK inhibitors. Issue 1 (1st January 2017)

• Record Type: Journal Article
• Authors: Katz, Jason D.; Haidle, Andrew; Childers, Kaleen K.; Zabierek, Anna A.; Jewell, James P.; Hou, Yongquan; Altman, Michael D.; Szewczak, Alexander; Chen, Dapeng; Harsch, Andreas; Hayashi, Mansuo; Warren, Lee; Hutton, Michael; Nuthall, Hugh; Su, Hua-Poo; Munshi, Sanjeev; Stanton, Matt G.; Davies, Ian W.; Munoz, Ben; Northrup, Alan
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 27:Issue 1(2017)
• Page Start: 114
• Page End: 120
• Publication Date: 2017-01-01
• Subjects: MARK -- Kinase -- Tau -- Alzheimer's disease -- Pyrrolopyrimidinone; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2016.08.068
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: The initial structure activity relationships around an isoindoline uHTS hit will be described. Information gleaned from ligand co-crystal structures allowed for rapid refinements in both MARK potency and kinase selectivity. These efforts allowed for the identification of a compound with properties suitable for use as an in vitro tool compound for validation studies on MARK as a viable target for Alzheimer's disease.