Ravez Séverine, Castillo-Aguilera Omar, Depreux Patrick, Goossens Laurence
Univ Lille, Institut de Chimie Pharmaceutique Albert Lespagnol 3 rue du Professeur Laguesse , B.P. 83, 59006 Lille , France +33 3 20 96 47 02 ; +33 3 20 96 49 06 ;
Expert Opin Ther Pat. 2015 Jul;25(7):789-804. doi: 10.1517/13543776.2015.1039512. Epub 2015 Apr 24.
Quinazoline is one of the most studied moieties in medicinal chemistry due to the wide range of biological properties such as the anticancer, antibacterial, anti-inflammatory, antimalarial and antihypertensive activities. During the past decades, several patents and articles have been published in international peer-reviewed literature regarding the discovery and development of original and promising quinazoline derivatives for cancer treatment. Although quinazolines are well known to inhibit EGFR, there is also a large panel of other therapeutic protein targets.
This review summarized the new patents and articles published about quinazoline derivatives as anticancer drugs since 2011.
Since 2011, a lot of quinazoline compounds have shown EGFR inhibition. Unlike the first-generation EGFR inhibitors, they inhibit both wild-type and mutated EGFR. In recent years, a number of studies on quinazoline synthesis have been reported and used by several medicinal chemistry groups for better and easier development of new derivatives. Therefore, several patents have been approved for the use of quinazoline compounds as inhibitors of other kinases, histone deacetylase, Nox and some metabolic pathways. Because of the large number of proteins targeted, some high structural diversity is observed in patented quinazoline compounds. Due to the vast applications of quinazoline derivatives, development of novel quinazoline compounds as anticancer drugs remains a promising field.
喹唑啉是药物化学中研究最多的基团之一,因其具有广泛的生物学特性,如抗癌、抗菌、抗炎、抗疟疾和抗高血压活性。在过去几十年中,国际同行评审文献中发表了多篇专利和文章,涉及发现和开发用于癌症治疗的新型且有前景的喹唑啉衍生物。尽管喹唑啉因抑制表皮生长因子受体(EGFR)而广为人知,但它还有大量其他治疗性蛋白质靶点。
本综述总结了自2011年以来发表的关于喹唑啉衍生物作为抗癌药物的新专利和文章。
自2011年以来,许多喹唑啉化合物已显示出对EGFR的抑制作用。与第一代EGFR抑制剂不同,它们既能抑制野生型EGFR,也能抑制突变型EGFR。近年来,已有多项关于喹唑啉合成的研究报道,并被多个药物化学团队用于更好、更便捷地开发新衍生物。因此,多项关于喹唑啉化合物作为其他激酶、组蛋白去乙酰化酶、Nox和一些代谢途径抑制剂的专利已获批准。由于靶向的蛋白质数量众多,在已获专利的喹唑啉化合物中观察到了高度的结构多样性。鉴于喹唑啉衍生物的广泛应用,开发新型喹唑啉化合物作为抗癌药物仍然是一个有前景的领域。