Synthesis of Arginine-vasopressins, Modified in Positions 1 and 2, as Antagonists of the Vasopressor Response to the Parent Hormone

Article abstract of DOI:10.1021/jm00398a018

In an attempt to determine some of the structural features in position 1 that account for antivasopressor activity, eight new 1-(β,β-dialkyl-substituted) analogues of 1-(3-mercaptopropanoic acid)-8-arginine-vasopressin and 1-(3-mercaptopropanoic acid)-2-O-methyltyrosine-8-arginine-vasopressin have been designed and synthesized.The protected precursors required for these peptides were obtained by a combination of solid-phase and solution methods.Some of the reported analogues, namely 1-(1-mercapto-4-methylcyclohexaneacetic acid)-8-arginine-vasopressin, 1-(1-mercapt-4-methylcyclohexaneacetic acid)-2-O-methyltyrosine-8-arginine-vasopressin, 1-(4-tert-butyl-1-mercaptocyclohexaneacetic acid)-8-arginine-vasopressin, 1-(4-tert-butyl-1-mercaptocyclohexaneacetic acid)-2-O-methyltyrosine-8-arginine-vasopressin, 1-(1-mercapto-4-phenylcyclohexaneacetic acid)-8-arginine-vasopressin and 1-(1-mercapto-4-phenylcyclohexaneacetic acid)-2-O-methyltyrosine-8-arginine-vasopressin, are among the most potent and selective antagonists of the vasopressor responce to arginine-vasopressin reported to date.