Synthesis and biological activity of N-terminus modified angiotensin II analogues

Article abstract of DOI:10.1016/0223-5234(90)90183-4

Semi-peptidic analogues of the angiotensin II (AII) antagonist AII have been prepared by the solid phase method and, for some steps, by synthesis in solution.In the modified analogues 4-15, the N-terminal di- or tripeptidic fragments (Asp-Arg or Asp-Arg-Val) in AII was replaced by non-peptidic moieties featuring amino or guanidino groups as substituent of simple alkyl spacers of various lengths.The compounds synthesized have been tested for their ability to produce an AII-like contraction and/or to inhibit AII-induced contractions in isolated rabbit aortae.All of them were found devoid of agonistic activity and most retained significant antagonistic activity in this assay.Analogue 5 antagonized AII-induced blood pressure effect in the anesthetized rat when infused at 30 μg/kg/min.The structure-activity relationships for these compounds are discussed.