Discovery of pyrrolo[2,3-d]pyrimidine-based molecules as a Wee1 inhibitor template.

ABSTRACT

In the past decade, Wee1 inhibition has received widespread attention as a cancer therapy. Our research aims to discover effective, selective and drug-like Wee1 inhibitors. Herein, a series of compounds with pyrrolo[2,3-d]pyrimidine-based heterocycles were designed, synthesized and confirmed to inhibit Wee1 kinase. The inhibitors afforded good potency in Wee1 Kinase inhibitory activity in enzymatic assays. These compounds showed strong proliferation inhibition against NCI-1299 cell lines and had acceptable pharmacokinetic properties. These derivatives are promising inhibitors that warrant further evaluation, towards the development of potential anticancer drug.