Investigation of biaryl heterocycles as inhibitors of Wee1 kinase. Issue 12 (15th June 2019)

• Record Type: Journal Article
• Authors: Mastracchio, Anthony; Lai, Chunqiu; Torrent, Maricel; Bromberg, Kenneth; Buchanan, Fritz G.; Ferguson, Debra; Bontcheva, Velitchka; Johnson, Eric F.; Lasko, Loren; Maag, David; Shoemaker, Alexander R.; Penning, Thomas D.
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 29:Issue 12(2019)
• Page Start: 1481
• Page End: 1486
• Publication Date: 2019-06-15
• Subjects: Wee1 -- Cdk1 -- Cdc2 -- G1 checkpoint -- G2/M checkpoint; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2019.04.017
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: In continuation of our previous research towards the discovery of potent, selective and drug-like Wee1 inhibitors, 2 novel series of biaryl heterocycles were designed, synthesized and evaluated. The new biaryl cores were designed to enable structure−activity exploration of substituents at C-8 or N-8 which were used for tuning compound properties and to improve compound profiles. The lead molecule 33 demonstrated a desirable pharmacokinetic profile and potentiated the anti-proliferative activity of irinotecan in vivo when dosed orally in the human breast MX-1 xenograft model.