Investigation of biaryl heterocycles as inhibitors of Wee1 kinase.

Basic Information

ID: ALA4387719

Journal: Bioorg Med Chem Lett

Title: Investigation of biaryl heterocycles as inhibitors of Wee1 kinase.

Authors: Mastracchio A, Lai C, Torrent M, Bromberg K, Buchanan FG, Ferguson D, Bontcheva V, Johnson EF, Lasko L, Maag D, Shoemaker AR, Penning TD.

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.

CiteXplore: 31014911

DOI: 10.1016/j.bmcl.2019.04.017

Patent ID: