In vivo and in vitro SAR of tetracyclic MAPKAP-K2 (MK2) inhibitors. Part II

The synthesis and SAR of tetracyclic MK2 inhibitors is reported. Spirocyclopropyl- and spiroazetidine groups attached to the δ-ring produced potent MK2-inhibitors with oral activity in the acute LPS-induced TNFα release model in mice. Compound 13E showed significant reduction of swelling and histological scores in two chronic arthritis models upon oral administration.