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Molecules 2016, 21(12), 1693;

Design and Synthesis of Vandetanib Derivatives Containing Nitroimidazole Groups as Tyrosine Kinase Inhibitors in Normoxia and Hypoxia

Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Peking Union Medical College & Chinese Academy of Medical Sciences, Tianjin 300192, China
Chongqing Technical Center for Drug Evaluation & Certification, Chongqing 400014, China
School of Petrochemical Engineering, Changzhou University, Changzhou 213164, China
Authors to whom correspondence should be addressed.
Academic Editor: Diego Muñoz-Torrero
Received: 19 October 2016 / Revised: 4 December 2016 / Accepted: 6 December 2016 / Published: 14 December 2016
(This article belongs to the Section Medicinal Chemistry)
Full-Text   |   PDF [2396 KB, uploaded 14 December 2016]   |  


Sixteen novel epidermal growth factor receptor (EGFR)/vascular endothelial growth factor (VEGF)-2 inhibitors (nitroimidazole-substituted 4-anilinoquinazoline derivatives (16ap)) were designed and prepared via the introduction of a nitroimidazole group in the piperidine side chain and modification on the aniline moiety of vandetanib. Preliminary biological tests showed that comparing with vandetanib, some target compounds exhibited excellent EGFR inhibitory activities and anti-proliferative over A549/H446 cells in hypoxia. Meanwhile, several of the above compounds demonstrated better bioactivity than vandetanib in VEGF gene expression inhibition. Owing to the excellent IC50 value (1.64 μmol/L), the inhibition ratios of 16f over A549 and H446 cells were 62.01% and 59.86% at the concentration of 0.5 μM in hypoxia, respectively. All of these results indicated that 16f was a potential cancer therapeutic agent in hypoxia and was worthy of further development. View Full-Text
Keywords: tyrosine kinase inhibitor; vandetanib; nitroimidazole; hypoxia tyrosine kinase inhibitor; vandetanib; nitroimidazole; hypoxia

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Wei, H.; Li, D.; Yang, X.; Shang, H.; Fan, S.; Li, Y.; Song, D. Design and Synthesis of Vandetanib Derivatives Containing Nitroimidazole Groups as Tyrosine Kinase Inhibitors in Normoxia and Hypoxia. Molecules 2016, 21, 1693.

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