Cinnamic acids and mono-substituted benzoic acids as useful capping groups for the preparation of hNK2 receptor antagonists.
Porcelloni M, D'Andrea P, Altamura M, Catalioto RM, Giuliani S, Meini S, Fattori D.
NK(2) antagonists have been reported to be potentially useful for the treatment of a number of chronic diseases, such as asthma, irritable bowel syndrome, cystitis, and depression. Starting from an in-house prepared library of capped dipeptides, we have identified a series of molecules with subnanomolar binding affinity for the hNK(2) receptor. These molecules are composed by three well-defined regions: a planar aromatic acyl system as N-terminal capping group, a rigid and quite lipophilic core, and a flexible and relatively hydrophilic C-terminal capping group. Here we report how we were able to manipulate the N-terminal capping group to obtain significant in vivo activity after i.v. and i.d. administration.