Bioorganic and Medicinal Chemistry p. 6674 - 6679 (2017)
Update date:2022-09-26
Topics:
Li, Jieming
Gu, Weijie
Bi, Xinzhou
Li, Huilan
Liao, Chen
Liu, Chunxia
Huang, Wenlong
Qian, Hai
Both c-Met and VEGFR-2 are important targets for cancer therapies. Here we report a series of potent dual c-Met and VEGFR-2 inhibitors bearing thieno[2,3-d]pyrimidine scaffold. The cell proliferation assay in vitro demonstrated that most target compounds had inhibition potency both on c-Met and VEGFR-2 with IC50 values in nanomolar range, especially compound 12j and 12m. Based on the further enzyme assay in vitro, compound 12j was considered as the most potent one, the IC50 values of which were 25 nM and 48 nM for c-Met and VEGFR-2, respectively. Following that, we docked the compound 12j with the proteins c-Met and VEGFR-2, and interpreted the SAR of these analogues. All the results indicate that 12j is a dual inhibitors of c-Met and VEGFR-2 that holds promising potential.
View Morewebsite:http://www.np-chem.com
Contact:0086-25-52346877
Address:199, Jian Ye Road, Nanjing, China
Contact:+86-27-87204219, +86-27-87215023
Address:2402, HuiGu Space-time Building, 8 Forest Road, East Lake Hi-Tech Development Zone
Contact:18669908765
Address:Zibo City, Shandong Province, P.R.China
Shanghai Anya Chemicals Co.,Ltd
Contact:+86 21 51087925
Address:Room 1101, No.1, Lane 111, Fudu Road, Shanghai, China
Shanghai shibo Chemical Co., Ltd
Contact:+86-021-60753516
Address:688 Qiushi Road, Jinshan High-tech Park, Shanghai, China,201512
Doi:10.1021/jo020753z
(2003)Doi:10.1021/ja01847a066
(1941)Doi:10.1002/1521-3773(20020503)41:9<1584::AID-ANIE1584>3.0.CO;2-Y
(2002)Doi:10.1016/j.catcom.2013.07.020
(2013)Doi:10.1081/SCC-120003633
(2002)Doi:10.1039/J19670000880
()