Serine and D-serine position-1 substituted angiotensin II analogues. Synthesis using new 2,3,5,6-tetrafluorophenyl active esters and biological activities.

[Ser1]- (32), [D-Ser1]-(29), [Ser1, Leu8]-(31), and [D-Ser1, Leu8] angiotensin II (30) were synthesized by a repetitive method in solution using new protected amino acid 2,3,5,6- tetrafluorophenyl active esters. 32 and 29 were agonists, and 31 and 30 were specific antagonists to angiotensin II (AII) receptors determined by the rabbit aortic strip (RAS) and rat blood pressure (RBP) assays. It was found that the hydroxymethyl side chains of serine and D-serine in position-1 has an important influence on the agonistic activity of the analogues. The pressor activities of 32 and 29 were 129 and 314%, respectively, as potent as AII. On the other hand, 31 and 30 were effective in antagonizing the AII-induced contraction of RAS and rise in RBP.