Design, Synthesis, and Biological Evaluation of 3,4-Dihydroisoquinolin-1()-one Derivatives as Protein Arginine Methyltransferase 5 Inhibitors for the Treatment of Non-Hodgkin's Lymphoma.

Through catalyzing the transfer of methyl groups onto the guanidinium of arginine, protein arginine methyltransferase 5 (PRMT5) was essential to the cell growth of cancer cells. By utilizing a scaffold hopping strategy, a novel series of 3,4-dihydroisoquinolin-1()-one derivatives were designed and synthesized. Through a systematic SAR study, demonstrated excellent PRMT5 inhibitory activity, potent antiproliferative activity against Z-138, favorable pharmacokinetic profiles, and low hERG toxicity.