SYNTHESIS AND CHARACTERIZATION OF PSEUDOPEPTIDE BRADYKININ B2 RECEPTOR ANTAGONISTS CONTAINING THE 1,3,8-TRIAZASPIRO[4,5]DECAN-4-ONE RING-SYSTEM

A series of pseudopeptides containing alkyl-, cycloalkyl-, aryl-, and aralkyl-substituted 1,3,8-triazaspiro[4.5]decan-4-one-3-acetic acids a s amino acid surrogates to replace the Pro(2)-Pro(3)-Gly(4)-Phe(5) sec tion of the peptide bradykinin B2 receptor antagonist [Pro(3), Phe(5)] HOE 140 ro(3)-Gly(4)-Phe(5)-Ser(6)-D-Tic(7)-Oic(8)-Arg(9)) were prepar ed. These psuedopeptides were examined in vitro for their B2 receptor affinities as well as for their ability to block bradykinin mediated a ctions in, vivo. Two compounds in particular, NPC 18521 (I) and NPC 18 688 (V) were quite potent in these latter assays, indicating that a si gnificant portion of this prototypical second generation decapeptide a ntagonist can be replaced with a more compact nonpeptide molecule.