[发明专利]含2‑甲基‑4‑氧代喹唑啉‑6‑基的查耳酮类似物及其制备方法和用途

说明书

技术领域

本发明涉及药物化学领域，更具体地说涉及含2-甲基-4-氧代喹唑啉-6-基的查耳酮类似物，及其制备方法和和它们在抗肿瘤药物中的应用。

背景技术

1,3-二芳基-2-丙烯-1-酮(1,3-diaryl-2-propen-1-ones)，俗称查耳酮(chalcone)，是植物中一类重要的次级代谢产物以及合成黄酮和异黄酮的天然前体。查耳酮由A、B两个芳香环，以及连接两环的α,β-不饱和羰基体系所构成。文献中通常将与羰基相连接的芳环称为A环，而与碳-碳双键相连的称为B环。研究表明，天然或合成的查耳酮类化合物具有广泛的药理学活性，其中包括抗肿瘤活性[Zhu,C.；Zuo,Y.；Wang,R.；Liang,B.；Yue,X.；Wen,G.；Shang,N.；Huang，L.；Chen，Y.；Du，J.；Bu，X.Discovery of potent cytotoxic ortho-aryl chalcones as new scaffold targeting tubulin and mitosis with affinity-based fluorescence.J.Med.Chem.2014,57,6364-6382][Venkateswararao,E.；Sharma,V.K.；Yun,J.；Kim,Y.；Jung,S.H.Anti-proliferative effect of chalcone derivatives through inactivation of NF-κB in human cancer cells.Bioor.Med.Chem.2014,22,3386–3392][Mai,C.W.；Yaeghoobi,M.；Abd-Rahman，N.；Kang,Y.B.；Pichika,M.R.Chalcones with electron-withdrawing and electron-donating substituents:Anticancer activity against TRAIL resistant cancer cells,structure-activity relationship analysis and regulation of apoptotic proteins.Eur.J.Med.Chem.2014,77,378-387][Singh,P.；Anand,A.；Kumar.V.Recent developments in biological activities of chalcones:A mini review.Eur.J.Med.Chem.2014,85,758–777][Sahu,U.；Panda,N.C.；Ravikumar,B.V.V.；Kumar,A.Activity of chalcone and its derivatives-a Review.Pharma Tutor Magazine 2014,2,62–75]。