多靶点抗肿瘤药物索拉非尼结构改造研析进展.pdfVIP

药学学报 Acta Pharmaceutica Sinica 20 12, 47 (9): 1111 1119 ·1111 · ·综述· 多靶点抗肿瘤药物索拉非尼结构改造的研究进展 1, 2 1 2 1* 姚建文 , 孙 伟 , 陈 静 , 徐文方 ( 1. 山东大学药学院, 山东 济南 2500 12; 2. 烟台大学 学院, 山东 烟台 264005) 摘要: 索拉非尼是首个上市的口服多靶点激酶抑制剂, 可以抑制与肿瘤增殖和血管生长相关的多种激酶, 包括Raf、VEGFR 、PDGFR 和kit 等。由于其多靶点机制、广谱、耐受性好和易于联合用药等优势, 众多学者致 力于索拉非尼结构改造的研究, 期望发现新的靶向抗肿瘤 物。本文从生物电子等排和骨架迁跃 个方面综述 了近年来索拉非尼结构改造研究的最新进展, 并简要总结了这些化合物的构效关系。 关键词: 索拉非尼衍生物; 结构改造; 构效关系; 抗肿瘤药物 中图分类号: R9 16 文献标识码: A 文章编号: 05 13-4870 (20 12) 09- 1111-09 Advances in the study of structural modifications of multi-target anticancer drug sorafenib 1, 2 1 2 1* YAO Jian-wen , SUN Wei , CHEN Jing , XU Wen-fang (1. School of Pharmaceutical Sciences, Shandong University, J inan 250012, China; 2. School of Pharmacy, Yantai University, Yantai 264005, China) Abstract: Sorafenib, the first oral multikinase inhibitor, can inhibit several kinases involved in tumor proliferation and angiogenesis including Raf, VEGFR, PDGFR, kit and so on . Due to the advantages of multi- mechanisms, broad-spectrum anticancer potency, and well-tolerated results in combination trials, more and more researchers have focused on the optimization of sorafenib in order to develop novel multi-targeted anticancer drugs. The present paper reviews the development of modification of sorafenib in recent years from two aspects: bio-isosterism and scaffold hopping. The structure-activity relation