Synthesis and Biological Activities of Substance P Antagonists

Article abstract of DOI:10.1021/jm00353a008

Several substance P analogues containing various D-amino acid modifications have been synthesized by the solid-phase procedure, detached from the solid support by ammonolysis, and purified by gel filtration combined with reversed-phase chromatography.Three compounds were fair to very potent competitive antagonists of substance P on three bioassays, i.e., guinea pig ileum, rabbit mesenteric vein, and guinea pig trachea. 6,D-Trp¹⁰>SP(6,11) is a reasonable antagonist in all three bioassays and 4,D-Trp^7,9>SP(4-11) is a very potent competitive antagonist with pA₂ values ranging around 6.0.