Unknown

Dataset Information

0

Discovery of Potent c-MET Inhibitors with New Scaffold Having Different Quinazoline, Pyridine and Tetrahydro-Pyridothienopyrimidine Headgroups.


ABSTRACT: Cellular mesenchymal-epithelial transition factor (c-MET) is closely linked to human malignancies, which makes it an important target for treatment of cancer. In this study, a series of 3-methoxy-N-phenylbenzamide derivatives, N-(3-(tert-butyl)-1-phenyl-1H-pyrazol-5-yl) benzamide derivatives and N¹-(3-fluoro-4-methoxyphenyl)-N³-(4-fluorophenyl) malonamide derivatives were designed and synthesized, some of them were identified as c-MET inhibitors. Among these compounds with new scaffolds having different quinazoline, pyridine and tetrahydro-pyridothienopyrimidine head groups, compound 11c, 11i, 13b, 13h exhibited both potent inhibitory activities against c-MET and high anticancer activity against tested cancer cell lines in vitro. In addition, kinase selectivity assay further demonstrated that both 13b and 13h are potent and selective c-MET inhibitors. Molecular docking supported that they bound well to c-MET and VEGFR2, which demonstrates that they are potential c-MET RTK inhibitors for cancer therapy.

SUBMITTER: Jiang Y 

PROVIDER: S-EPMC6272887 | biostudies-literature |

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC8201751 | biostudies-literature
| S-EPMC6232652 | biostudies-literature
| S-EPMC6271681 | biostudies-literature
| S-EPMC4857548 | biostudies-literature
| S-EPMC4434476 | biostudies-literature
| S-EPMC7392372 | biostudies-literature
| S-EPMC4904267 | biostudies-literature
| S-EPMC5554905 | biostudies-literature
| S-EPMC8730469 | biostudies-literature
| S-EPMC6427567 | biostudies-literature