Journal of International Pharmaceutical Research 2017;44(6):575-579

doi:10.13220/j.cnki.jipr.2017.06.020

Synthesis and activity evaluation of novel tyrosine kinase inhibitors

Hongpeng YANG ; Gang WANG ; Tao PENG ; Xiaoxue WEN ; Jianyun YANG ; Yunbo SUN ; Shuchen LIU ; Shouguo ZHANG ; Lin WANG

Keywords

protein tyrosine kinase inhibitor; design and synthesis; L029

Country

China

Language

Chinese

Abstract

Objective To design and synthesize compounds with protein tyrosine kinase(PTK)inhibitory activity with L029 as the lead compound. Methods L029 derivatives were designed and synthesized from L029 by reduction and/or substitution with the 3-dimethylamino-1-propyl,methyl acetate,methyl propionate in its active H and other sites. PTK activity was measured by enzyme-linked immunosorbent assay(ELISA). The inhibitory rate was calculated to screen out the compounds with PTK inhibitory activity. Re-sults Five target compounds were synthesized and their structures were confirmed by 1H NMR and MS. Three compounds T2,T3 and T5 were screened out with strong PTK inhibitory activity. Conclusion The synthetic routes of the target compounds are simple with mild reaction condition,and 3 compounds show strong inhibitory activity by ELISA. These results can provide reference for the further design and synthesis of this kind of molecules.