Two highly effective V1/V2 antagonists of vasopressin containing novel thioacids at position 1

J Pharm Pharmacol. 1991 Jan;43(1):40-2. doi: 10.1111/j.2042-7158.1991.tb05445.x.

Abstract

In an attempt to develop more effective and selective V1/V2 antagonists of arginine vasopressin (AVP), two analogues have been designed and synthesized. In position 1 they contain thioacids that include a heteroatom in the cyclohexane ring. The 4-thio-4-tetrahydrothiopyraneacetic acid modification of position 1 used in one of them had advantages over the 1-mercaptocyclohexaneacetic acid substituted compound used as reference. The new compound was weaker at lower doses, but elicited a greater response at higher doses, whereas the reference compound reached its plateau earlier. Although the 4-thio-4-tetrahydropyraneacetic acid substitution used in the second compound resulted in a less potent analogue on a weight basis, this substitution also confers enhanced overall efficacy in terms of magnitude of effect.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Arginine Vasopressin / analogs & derivatives*
  • Arginine Vasopressin / antagonists & inhibitors*
  • Arginine Vasopressin / chemical synthesis
  • Arginine Vasopressin / pharmacology
  • Male
  • Rats
  • Rats, Inbred Strains
  • Structure-Activity Relationship

Substances

  • Arginine Vasopressin
  • argipressin, 1-(4-thio-4-tetrahydropyranoacetic acid)-O-Et-Tyr(2)-Val(4)-
  • argipressin, 1-(4-thio-4-tetrahydrothiopyranoacetic acid)-O-Et-Tyr(2)-Val(4)-