Design and preparation of 2-benzamido-pyrimidines as inhibitors of IKK

The design, synthesis, and the biological evaluation of 2-benzamido-pyrimidines as novel IKK inhibitors are described. By optimization of the lead compound 3, compounds 16 and 24 are identified as good inhibitors of IKK2 with IC50 values of 40 and 25 nM, respectively. Compound 16 also demonstrated significant in vivo activity in an acute model of cytokine release.

A series of 4-substituted 2-benzamido-pyrimidines has been synthesized and evaluated for their IKK2 inhibitory activities.Figure optionsDownload as PowerPoint slide