Design, Synthesis, and Biological Evaluation of Axitinib Derivatives

• Published in: Molecules (Basel, Switzerland) Switzerland), 2018-03, Vol.23 (4), p.747
• Main Authors: Wei, Na, Liang, Jianqing, Peng, Shengming, Sun, Qiang, Dai, Qiuyun, Dong, Mingxin
• Format: Article
• Language: English
• Subjects: Angiogenesis; Angiogenesis Inhibitors - chemical synthesis; Angiogenesis Inhibitors - chemistry; Angiogenesis Inhibitors - pharmacology; Apoptosis; axitinib; Benzene; Biological activity; Biological effects; Carcinoma, Renal Cell - metabolism; Cell Line, Tumor; Enzyme inhibitors; Humans; Imidazoles - chemical synthesis; Imidazoles - chemistry; Imidazoles - pharmacology; Indazoles - chemical synthesis; Indazoles - chemistry; Indazoles - pharmacology; inhibitor; Inhibitor drugs; Kidney cancer; Kidney Neoplasms - metabolism; Medical treatment; Metastases; Protein Kinase Inhibitors - chemical synthesis; Protein Kinase Inhibitors - chemistry; Protein Kinase Inhibitors - pharmacology; Pyridines; Renal cell carcinoma; Solid tumors; synthesis; Targeted cancer therapy; tumor; Vascular Endothelial Growth Factor Receptor-2 - metabolism; Vascular endothelial growth factor receptors; VEGFR-2
• ISSN: 1420-3049; 1420-3049
• 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.