Design and synthesis of 1-aryl-5-anilinoindazoles as c-Jun N-terminal kinase inhibitors

The structure-activity relationship study of a 5-aminoindazole series of JNK3 kinase inhibitors is reported. Starting from HTS screening hit 1, cyclization led to an indazole series with improved in vitro activity. The lead compound identified (5r) is a potent JNK3 inhibitor with good exposure in mouse which makes it a suitable in vivo probe to interrogate the functions of JNK3 kinase in animal models of disease.