Analogs of Arginine-Vasopressin Substituted in Position 2 with L-4-Cl-Phenylalanine or D-Phenylglycine

Eight new compounds were designed, synthesized and bioassayed as a part of our studies on the structure-activity relationship of arginine-vasopresine (AVP) analogs. Tyrosine in position 2 of AVP, dAVP, [Cpp1]AVP and [Cpp1,Val4]AVP was substituted by L-4-chlorophenylalanine (4-Cl-Phe) or D-phenylglycine [D-Gly(Phe)] and the effect of these changes on agonistic/antagonistic activity in uterotonic and pressor test was followed. All but one of these analogs were found inhibitory in uterotonic test, however in most cases their potency was fairly low. As to the pressor activity the agonistic potency of the 4-Cl-Phe substituted analogs was essentially the same as having 4-F-Phe in position 2. As far as the potency of antagonists is concerned, 4-Cl-Phe peptides showed significantly higher potency than the 4-F-Phe analogs. All compounds containing D-phenylglycine in position 2 were inactive in the pressor test.