Dipartimento di Scienze Farmaceutiche, Università degli Studi di Padova, via Marzolo 5, 35131 Padova, Italy.
Expert Opin Ther Pat. 2012 Mar;22(3):223-52. doi: 10.1517/13543776.2012.665876. Epub 2012 Mar 12.
Due to the increase in knowledge about cancer pathways, there is a growing interest in finding novel potential drugs. Quinazoline is one of the most widespread scaffolds amongst bioactive compounds. A number of patents and papers appear in the literature regarding the discovery and development of novel promising quinazoline compounds for cancer chemotherapy. Although there is a progressive decrease in the number of patents filed, there is an increasing number of biochemical targets for quinazoline compounds.
This paper provides a comprehensive review of the quinazolines patented in 2007 - 2010 as potential anticancer agents. Information from articles published in international peer-reviewed journals was also included, to give a more exhaustive overview.
From about 1995 to 2006, the anticancer quinazolines panorama has been dominated by the 4-anilinoquinazolines as tyrosine kinase inhibitors. The extensive researches conducted in this period could have caused the progressive reduction in the ability to file novel patents as shown in the 2007 - 2010 period. However, the growing knowledge of cancer-related pathways has recently highlighted some novel potential targets for therapy, with quinazolines receiving increasing attention. This is well demonstrated by the number of different targets of the patents considered in this review. The structural heterogeneity in the patented compounds makes it difficult to derive general pharmacophores and make comparisons among claimed compounds. On the other hand, the identification of multi-target compounds seems a reliable goal. Thus, it is reasonable that quinazoline compounds will be studied and developed for multi-target therapies.
由于对癌症途径的认识不断增加,人们越来越感兴趣于寻找新的潜在药物。喹唑啉是生物活性化合物中最广泛的支架之一。文献中出现了许多关于发现和开发新型有希望的用于癌症化疗的喹唑啉化合物的专利和论文。尽管提交的专利数量逐渐减少,但针对喹唑啉化合物的生化靶点数量却在增加。
本文综述了 2007 年至 2010 年作为潜在抗癌剂的已获专利的喹唑啉。还包括了发表在国际同行评议期刊上的文章的信息,以提供更全面的概述。
从 1995 年到 2006 年,作为酪氨酸激酶抑制剂的 4-苯胺基喹唑啉主导了抗癌喹唑啉领域。这一时期进行的广泛研究可能导致在 2007 年至 2010 年期间提交新专利的能力逐渐下降。然而,对癌症相关途径的日益了解最近突显了一些新的潜在治疗靶点,喹唑啉受到了越来越多的关注。这一点在本综述中考虑的专利的不同靶点数量上得到了很好的证明。专利化合物的结构异质性使得难以得出一般药效团并对所声称的化合物进行比较。另一方面,鉴定多靶点化合物似乎是一个可靠的目标。因此,喹唑啉化合物将被研究并开发用于多靶点治疗是合理的。