Synthesis of 5-aryl-4-cyano-1H-1, 2, 3-triazoles and biological evaluation of their inhibitory action on tyrosine kinase.
- Author:
Wen-Jie LI
1
;
Su-Fang LIU
;
Zuan-Guang CHEN
;
Zhi-Yi CHENG
Author Information
1. School of Pharmaceutical Science, Sun Yat-sen University, Guangzhou 510006, China.
- Publication Type:Journal Article
- MeSH:
Breast Neoplasms;
metabolism;
pathology;
Cell Line, Tumor;
Cell Proliferation;
drug effects;
Crystallization;
Crystallography, X-Ray;
Female;
Humans;
Phosphorylation;
Protein-Tyrosine Kinases;
antagonists & inhibitors;
metabolism;
Receptor, ErbB-2;
antagonists & inhibitors;
metabolism;
Triazoles;
chemical synthesis;
chemistry;
pharmacology
- From:
Acta Pharmaceutica Sinica
2009;44(12):1371-1375
- CountryChina
- Language:Chinese
-
Abstract:
5-Aryl-4-cyano-1H-1, 2, 3-triazoles bearing a variety of substituting groups on 5-phenyl were synthesized. Their structures were established by MS, IR and 1H NMR spectra. The crystal structures of compounds 3f and 3m were determined by X-ray diffraction analysis. The active H of the triazole was on 1-N from the crystal structures. The compounds, designed as HER2 tyrosine kinase inhibitors, were screened for bioactivity of growth-inhibition of breast cancer MDA-MB-453 cells. The lowest IC50 value of inhibiting HER2 tyrosine kinase phosphorylation in breast cancer cells is 6.6 micromol x L(-1). The inhibiting-growth of breast cancer cells was enhanced from electron-drawing groups joining 5-phenyl on the triazole.
