ChemInform Abstract: Design and Synthesis of Antagonists of Substance P.

ChemInform Abstract

The known antagonist (IIa) (Spantide) which is an analogue of substance P (I) serves as reference antagonist for the design of 47 new peptides - e.g. (IIb), (IIc), (III)-(V) - toward the goal of more potent inhibitors. Designs emphasize analogues with D-Trp⁷, D-Trp⁹, D-Trp¹⁰, D-pClPhe¹⁰, Nle¹¹, Leu¹¹, Ile¹¹, and Met¹¹. The compounds are synthesized by the solid phase method. - Twenty-one antagonists are superior in potency to that of (IIa); the best is (IIIb) which requires a 255-fold increase in SP concentration to give 50% of the maximum response at a concentration of 10^-5 M of the antagonist; this potency is ca. 5 times that of (IIa). (Tables).