SYNTHESIS AND SOME PHARMACOLOGICAL PROPERTIES OF 7 NEW ANALOGS OF AAA-D-TYR(ET)-PHE-VAL-ASN-ABU-PRO-ARG-ARG-NH2, A POTENT LINEAR ANTAGONISTOF V-2 RECEPTORS

We have synthesized seven new analogues of potent V-2/V-1 antagonist n amely: adamanta-neacetyl-D-Tyr(Et)-Phe-Val- Asn-Abu-Pro-Arg-Arg-NH2 (I ). Four of them were designed by substitution of positions 2 or 3 with L- or D-1,2,3,4-tetrahydroisoquinolineacarboxylic acid. One peptide w as designed by replacement of Phe(3) residue by L-beta-thienylalanine (Thi). Finally, we synthesized two compounds in which we constructed a disulphide bridge on the C-terminal end of the model peptide I. The a nti-antidiuretic activity of analogues was evaluated by their ability to inhibit the antidiuretic effect of endogenous arginine-vasopressin (AVP). The antipressor potency of peptides was assayed by their abilit y to inhibit the presser response to exogenous AVP. The modifications proposed are incompatible with biological potency, particularly anti-V -2 activity. Nevertheless, two of the new analogues are potent vasopre ssor antagonists.