[Conformational analysis of peptide antagonists in the design of pseudopeptide and non-peptide antagonists]

The comparative conformational analysis of four Substance P antagonists (NK1-) having different chemical structures allowed to formulate an hypothesis for a peptidic NK1 pharmacophore. The salient features of this pharmacophore (three aromatic groups and two carbonyl functions) belong to a beta-turn conformation. Thus, this kind of conformation might be the basis for the design of newer pseudo-peptidic and non-peptidic NK1 antagonists.