5426-59-5Relevant articles and documents
Visible light induced tandem reactions: An efficient one pot strategy for constructing quinazolinones using in-situ formed aldehydes under photocatalyst-free and room-temperature conditions
Xie, Zongbo,Lan, Jin,Zhu, Haibo,Lei, Gaoyi,Jiang, Guofang,Le, Zhanggao
supporting information, p. 1427 - 1431 (2020/11/02)
A facile tandem route has been developed for constructing quinazolinones from various aminobenzamides and in-situ generated aldehydes. Visible light was found to play a dual role: first oxidizes the alcohol to the aldehyde and then facilitates its cyclization with o-substituted aniline. Furthermore, alcohols are perfect alternatives to aldehydes because they are greener, more available, more economical, more stable, and less toxic than aldehydes. The first reaction step continuously provides material for the second step, which effectively reduces loss through volatilization, oxidation, and polymerization of the aldehyde, while avoiding its toxicity. A variety of quinazolinones can be prepared in the presence of visible light without any additional photocatalyst. The developed synthesis protocol proceeds with the merits of mild conditions, broad substrate scope, operational simplicity, and high atom efficiency, with an eco-energy source under metal-free, photocatalyst-free, and ambient conditions.
Discovery and development of extreme selective inhibitors of the ITD and D835Y mutant FLT3 kinases
Baska, Ferenc,Sipos, Anna,?rfi, Zoltán,Nemes, Zoltán,Dobos, Judit,Szántai-Kis, Csaba,Szabó, Eszter,Szénási, Gábor,Dézsi, László,Hamar, Péter,Cserepes, Mihály T.,Tóvári, József,Garamv?lgyi, Rita,Krekó, Marcell,?rfi, László
, (2019/10/16)
Aberrant activation of FMS-like tyrosine receptor kinase 3 (FLT3) is implicated in the pathogenesis of acute myeloid leukemia (AML) in 20–30% of patients. In this study we identified a highly selective (phenylethenyl)quinazoline compound family as novel potent inhibitors of the FLT3-ITD and FLT3-D835Y kinases. Their prominent effects were confirmed by biochemical and cellular proliferation assays followed by mice xenograft studies. Our modelling experiments and the chemical structures of the compounds predict the possibility of covalent inhibition. The most effective compounds triggered apoptosis in FLT3-ITD AML cells but had either weak or no effect in FLT3-independent leukemic and non-leukemic cell lines. Our results strongly suggest that our compounds may become therapeutics in relapsing and refractory AML disease harboring various ITD and tyrosine kinase domain mutations, by their ability to overcome drug resistance.
Novel Quinazolinone Inhibitors of ALK2 Flip between Alternate Binding Modes: Structure-Activity Relationship, Structural Characterization, Kinase Profiling, and Cellular Proof of Concept
Hudson, Liam,Mui, James,Vázquez, Santiago,Carvalho, Diana M.,Williams, Eleanor,Jones, Chris,Bullock, Alex N.,Hoelder, Swen
, p. 7261 - 7272 (2018/09/04)
Structure-activity relationship and crystallographic data revealed that quinazolinone-containing fragments flip between two distinct modes of binding to activin receptor-like kinase-2 (ALK2). We explored both binding modes to discover potent inhibitors and characterized the chemical modifications that triggered the flip in binding mode. We report kinase selectivity and demonstrate that compounds of this series modulate ALK2 in cancer cells. These inhibitors are attractive starting points for the discovery of more advanced ALK2 inhibitors.
