Synthesis of novel melanocortin 4 receptor agonists and antagonists containing a succinamide core

A novel series of piperazines appended to a succinamide backbone were synthesized and found to have a high affinity for the melanocortin-4 receptor (IC50s ranging from <0.1 to 200 nM). Both agonists and antagonists of MC4R were prepared by modifying the groups attached to the right-hand side of the succinamide. This series also exhibits a high level of selectivity (up to 7000-fold) over mouse MC1R and human MC3R.