Design of potent and selective hybrid inhibitors of the mitotic kinase Nek2 : structure−activity relationship, structural biology, and cellular activity

We report herein a series of Nek2 inhibitors based on an aminopyridine scaffold. These compounds have been designed by combining key elements of two previously discovered chemical series. Structure based design led to aminopyridine (R)-21, a potent and selective inhibitor able to modulate Nek2 activity in cells.