Journal of International Pharmaceutical Research 2017;44(6):567-574,579

doi:10.13220/j.cnki.jipr.2017.06.019

Design,synthesis and activity evaluation of novel 2-indolone derivatives as the c-Met kinase inhibitors

Shouguo ZHANG ; Jieying WANG ; Haiyan YAN ; Tao PENG ; Xiaoxue WEN ; Gang WANG ; Yunbo SUN ; Shuchen LIU ; Lin WANG

Keywords

antitumor; c-Met kinase inhibitor; 2-indolone; design and synthesis

Country

China

Language

Chinese

Abstract

Objective To design and synthesize novel 2-indolone derivatives as the c-Met kinase inhibitors. Methods With c-Met kinase inhibitor SU11274 as lead compound,a series of 2-indolone derivatives were designed according to the concept of bioiso-sterism. Then the target compounds(10a-10r)were synthesized from 2-indolone through 5-chlorosulfonation with chlorosulfonic acid, sulfonamidation with intermediate 3,condensation with 6a-6h,7a-7h and 4a-4b,respectively. Their inhibitory activity against c-Met and proliferation of MCF-7 cells were evaluated. Results and Conclusion The designed compounds were successfully prepared and their structures were confirmed by 1H NMR and ESI-MS. Some compounds had certain inhibitory activity against c-Met and prolif-eration of MCF-7 cells. An initial structure-activity relationship analysis of these compounds was performed to provide useful informa-tion for further optimization of their structures.