Development of amino-pyrimidine inhibitors of c-Jun N-terminal kinase (JNK): Kinase profiling guided optimization of a 1,2,3-benzotriazole lead

Structure and kinase profiling guided the optimization of a CDK2 1,2,3-benzotriazole hit to give a series of indoles that are selective and potent dual JNK1 and 2 inhibitors. An advanced compound, 24f (IC50 JNK1/2 = 16/66 nM), was developed and suitable for in vivo pharmacological evaluation of JNK inhibition.