Synthesis and some pharmacological properties of three new analogues of arginine-vasopressin modified in positions 1,2,4 and 9.

We have synthesized three new analogues of arginine-vasopressin (AVP) to determine some of the structural features that account for antagonistic potency. These analogues are as follows: 4-glutamic acid (gamma-N,N-diethylamide)-8-arginine-vasopressin (I), N,N-diethylamide 1-(1-mercaptocyclohexaneacetic acid)-2-0-methyltyrosine- 4-glutamic acid (gamma-N,N-diethylamide)-8-arginine-vasopressin (II) and 1-(1-mercaptocyclohexaneacetic acid)-2-0-methyltyrosine-4-glutamic acid (gamma-glycine amide)-8-arginine-vasopressin (III). Analogues II and III are weak and moderate antagonists of the vasopressor response to AVP, respectively. Analogue III only exhibits a weak anti-antidiuretic activity. Analogue I lacks antagonistic effects in both systems.