ANALOGS OF ARGININE-VASOPRESSIN SUBSTITUTED IN POSITION-2 WITH L-4-CL-PHENYLALANINE OR D-PHENYLGLYCINE

Eight new compounds were designed, synthesized and bioassayed and bioa ssayed as a part of our studies on the structure-activity relationship of arginine-vasopressin (AVP) analogs. Tyrosine in position 2 of aVP, dAVP. [Cpp1]AVP and [Cpp1, Val4]AVP was substituted by L-4-chlorophen ylalanine (4-Cl-Phe) or d-phenylglycine [D-Gly(Ph)] and the effect of these changes on agonistic/antagonistic activity in uterotonic and pre ssor test was followed. All but one of these analogs were found inhibi tory in uterotonic test, however in most case 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 that having 4-F-Phe i n position 2. As far as the potency of antagonists is concerned, 4-Cl- Phe peptides showed significantly higher potency than the 4-F-Phe anal ogs. All compounds containing D-phenylglycine in position 2 were inact ive in the pressor test.