Design and biological evaluation of 3-substituted quinazoline-2,4(1H,3H)-dione derivatives as dual c-Met/VEGFR-2-TK inhibitors.

ABSTRACT: The dual c-Met/vascular endothelial growth factor receptor 2 (VEGFR-2) TK inhibition is a good strategy to overcome therapeutic resistance to small molecules VEGFR-2 inhibitors. In this study, we designed 3-substituted quinazoline-2,4(1H,3H)-dione derivatives as dual c-Met/VEGFR-2 TK inhibitors. We introduced new synthetic methods for reported derivatives of 3-substituted quinazoline-2,4(1H,3H)-dione 2a-g, in addition to the preparation of some new derivatives namely, 3 and 4a-j. Three compounds namely, 2c, 4b, and 4e showed substantial amount of inhibition for both c-Met and VEGFR-2 TK (IC₅₀ range 0.052-0.084 µM). Both compounds 4b, 4e showed HB with highly conserved residue Asp122

SUBMITTER: Hassan A 

PROVIDER: S-EPMC10026756 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature