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

The synthesis and SAR of tetracyclic MK2 inhibitors is reported. Tetracyclic lactams showed good selectivity profiles and potently inhibited TNFα release from hPBMCs. Tetracyclic ketone 14F was orally bioavailable and inhibited the LPS induced release of TNFα in mice.