Role of heterocycles in inhibition of VEGFR-2-a recent update (2019-2022)

The literature reveals that oncogenic protein kinase inhibition has been proved to be a successful anticancer approach. The vascular endothelial growth factor receptor (VEGFR) kinase plays an important role in angiogenesis and metastasis. VEGFR-2 has an upper hand in the angiogenesis process. Vascular endothelial growth factor activates VEGFR-2 which initiates tumor angiogenesis. In addition, VEGFRs are associated with numerous other diseases. Hence, inhibition of VEGFRs is an attractive approach for cancer treatment. In view of this, researchers designed and discovered small molecular heterocycle-based VEGFR-2 inhibitors and some of them have been approved by the Food and Drug Administration (FDA). However, these VEGFR-2 inhibitors pose adverse side effects such as cardiovascular problems, diarrhea, and renal function impairment. Research indicates that combination of certain pharmacophores exhibits excellent VEGFR inhibitory activity. In particular, combination of heterocycles paved the way to efficient VEGFR inhibitors. In this review, the research focusing on VEGFR inhibitory activity has been discussed along with the structure-activity relationship. In addition to emphasizing the most potent molecule among the set of designed molecules, structural features responsible for such an activity are described. This review may aid in designing potent VEGFR inhibitors. The review describes anti-VEGFR-2 activity of heterocycles including quinazoles, pyrimidines, isatin and azoles considering SAR for a given set of derivatives. Compounds with potent activity were emphasized with description of structural features.