Department of Chemistry, Xiangtan University, Xiangtan 411105, China.
Lab of Protein Engineering, Beijing Institute of Biotechnology, Beijing 100071, China.
Molecules. 2018 Mar 23;23(4):747. doi: 10.3390/molecules23040747.
Axitinib is an approved kinase inhibitor for the therapy of advanced metastatic renal cell carcinoma (RCC). It prevents angiogenesis, cellular adhesion, and induces apoptosis of cancer cells. Here, nine axitinib derivatives were designed by replacing the C=C moiety with the N=N group, and the substituted benzene or pyrrole analogs were considered to replace the pyridine ring. Biological activity results showed that most of nascent derivatives exhibited favorable VEGFR-2 kinase inhibitory activities, and , , , and behaved more potent anti-proliferative activities than axitinib. This novel series of compounds shows a potential for the treatment of solid tumors and other diseases where angiogenesis plays an important role.
阿昔替尼是一种已批准的激酶抑制剂，用于治疗晚期转移性肾细胞癌（RCC）。它可阻止血管生成、细胞黏附，并诱导癌细胞凋亡。在这里，通过将 C=C 部分用 N=N 基团替换，设计了 9 种阿昔替尼衍生物，并考虑用取代的苯或吡咯类似物替代吡啶环。生物活性结果表明，大多数新生成的衍生物表现出良好的 VEGFR-2 激酶抑制活性，并且 、 、 、 和 表现出比阿昔替尼更强的抗增殖活性。该系列化合物具有治疗实体瘤和其他血管生成起重要作用的疾病的潜力。
