Discovery of a series of benzopyrimidodiazepinone TNK2 inhibitors via scaffold morphing.
Basic Information
ID: ALA4699457
Journal: Bioorg Med Chem Lett
Title: Discovery of a series of benzopyrimidodiazepinone TNK2 inhibitors via scaffold morphing.
Authors: Li Z,Powell CE,Groendyke BJ,Gero TW,Feru F,Feutrill J,Chen B,Li B,Szabo H,Gray NS,Scott DA
Abstract: The protein kinase TNK2 (ACK1) is an emerging drug target for a variety of indications, in particular for cancer where it plays a key role transmitting cell survival, growth and proliferative signals via modification of multiple downstream effectors by unique tyrosine phosphorylation events. Scaffold morphing based on our previous TNK2 inhibitor XMD8-87 identified urea 17 from which we developed the potent and selective compound 32. A co-crystal structure was obtained showing 32 interacting primarily with the main chain atoms of an alanine residue of the hinge region. Additional H-bonds exist between the urea NHs and the Thr205 and Asp270 residues.
CiteXplore: 32739400
DOI: 10.1016/j.bmcl.2020.127456
Patent ID: ┄