Discovery of Novel [1,2,4]Triazolo[1,5-a]pyrimidine Derivatives as Novel Potent S-Phase Kinase-Associated Protein 2 (SKP2) Inhibitors for the Treatment of Cancer

Skp1-CUL1-ROC1-F-box E3 ubiquitin ligases' main component S-phase kinase-associated protein 2 (Skp2) is responsible for specifically recognizing ubiquitination-modified substrates to be degraded such as p27 and p21 in the case of binding with adaptor protein Cks1. Pharmacological inhibition of Skp2 has exhibited promising antitumor activity. Herein, we present the design and optimization of a series of [1,2,4]triazolo[1,5-