Synthesis and SAR of novel isoxazoles as potent c-jun N-terminal kinase (JNK) inhibitors

Isoxazoles 27 and 28 were discovered as novel c-jun N-terminal kinase (JNK) inhibitors with good biochemical potency and greatly improved selectivity over p38 as compared to the lead compound 3. Extensive SAR and an efficient route for the formation of bis- and tris-substituted isoxazole groups will be described.