Synthesis and biological activities of neurokinin pseudopeptide analogues containing a reduced peptide bond

Article abstract of DOI:10.1016/0223-5234(91)90134-9

A series of pseudopeptides, analogues of neurokinin selective agonists, in which a peptide bond was replaced by a (CH₂NH) bond were synthesized. The biological activities of these compounds were determined on selective pharmacological preparations: the dog carotid artery for NK-1, the rabbit pulmonary artery devoid of endothelium for the NK-2 and the rat portal vein for the NK-3 receptors. The results reported in this study indicate that insertion of a pseudopeptide bond in various positions of these selective agonists resulted in a great decrease in potency compared to the parent compounds. Furthermore, the selectivity of agonists is maintained by the use of a methylene amino group in position 9-10 (Sar) for the NK-1 or in position 7-8 (MePhe) for the NK-3 selective compound. The selectivity is greatly diminished for the NK-2 analogues.