Synthesis and biological evaluation of conformationally restricted derivatives of tryptophan as NK1/NK2 ligands

Chemical modifications on the NK1 competitive antagonist L-732,138, with a view to creating a dual NK1/NK2 ligand, led to the tryptophan derivative 1 possessing the protected Gly-Leu sequence of the C-terminus of substance P and neurokinin A. Modifications in the nature of the carbamate function increased the selectivity for the NK1 receptor, whereas the inclusion of the indole moiety in beta-carboline or carbazole rings decreased the affinity for both receptors. Free indolylmethyl and Cbz carbamate groups were shown to be essential for NK2 affinity.