Design,synthesis and activity evaluation of novel 2-indolone derivatives as the c-Met kinase inhibitors
10.13220/j.cnki.jipr.2017.06.019
- VernacularTitle:新型2-吲哚酮类c-Met激酶抑制剂的设计、合成及活性研究
- Author:
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
- From:
Journal of International Pharmaceutical Research
2017;44(6):567-574,579
- CountryChina
- 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.