Synthesis of arginine-vasopressins, modified in positions 1 and 2, as antagonists of the vasopressor response to the parent hormone

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Abstract
In an attempt to determine some of the structural features in position 1 that account for antivasopressor activity, eight new 1-(.beta.,.beta.-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 solutions methods. Some of the reported analogues, namely 1-(1-mercapto-4-methylcyclohexaneacetic acid)-8-arginine-vasopressin, 1-(1-mercapto-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 response to arginine-vasopressin reported to date.