1,2,3-Trisubstituted Cyclohexyl Substance P Antagonists: Significance of the Ring Nitrogen in Piperidine-Based NK-1 Receptor Antagonists.

Abstract A stereocontrolled synthesis of 1-benzyloxy-2-phenylcyclohexane derivatives containing polar substituents at C3 is described. These compounds, designed to test the role of the ring nitrogen in a related series of potent piperidine-based substance P antagonists, show similar NK-1 receptor affinity, indicating that the nitrogen may serve a largely structural role in N-substituted piperidine antagonists.