Collect. Czech. Chem. Commun. 1992, 57, 1960-1966

Acylation of the N-Terminus of B2 Bradykinin Antagonists with Bulky Substituents Dramatically Increases Potency

Bernard Lammeka, Yasushi Itob, Irene Gavrasb and Haralambos Gavrasb

a Department of Chemistry, University of Gdańsk, Sobieskiego 18, 80-952 Gdansk, Poland
b Hypertension Section and Department of Medicine, Thorndike Memorial Laboratory, Boston City Hospital and the Department of Medicine, University Hospital, Boston University School of Medicine, U.S.A.


While studying structural factors which can influence B2 antagonistic activity we designed and synthesized five new bradykinin (BK) antagonists. Two of them, namely Aaa[D-Arg0, Hyp3, D-Phe7, Leu8]BK and Aca[D-Arg0, Hyp3, D-Phe7, Leu8]BK are among the most potent B2-antagonists of exogeneous BK described to date. The remaining three analogs are also potent B2-antagonists. None of the new compounds contain Thi at position 5 and 8, a change that markedly reduces their cost. The new antagonists have obvious potential as valuable pharmacological tools in the investigation of the role of endogenous BK in cardiovascular regulation.