Synthesis of 8-D-arginine vasopressin analogues, modified in position 1 as antagonists of the vasopressor response to the parent hormone

Pol J Pharmacol Pharm. 1988 Jul-Aug;40(4):423-8.

Abstract

The synthesis of three new arginine vasopressin (AVP) analogues with changes at position 1 and 8 is reported. They are: 1-(1-mercapto-4-methylcyclohexaneacetic acid)-8-D-arginine-vasopressin, 1-(4-tert-butyl-1-mercaptocyclohexaneacetic acid)-8-D-arginine-vasopressin and 1-(1-mercapto-4-phenylcyclohexaneacetic acid)-8-D-arginine-vasopressin. They all proved to be potent and selective antagonists of the vasopressor response to AVP. They lacked antagonism in the antidiuretic assay (AD), but retained small agonism in this system. The Arg8 substitution instead of Arg8 in case of the described AVP analogues did not lead to any significant change of antagonistic potency or selectivity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arginine Vasopressin / analogs & derivatives*
  • Arginine Vasopressin / chemical synthesis
  • Arginine Vasopressin / pharmacology*
  • Blood Pressure / drug effects
  • Diuresis / drug effects
  • Drug Evaluation, Preclinical
  • Female
  • Rats
  • Rats, Inbred Strains
  • Structure-Activity Relationship

Substances

  • Arginine Vasopressin
  • argipressin, (1-mercapto-4-methylcyclohexaneacetic acid)(1)-
  • argipressin, (4-tert-butyl-1-mercaptocyclohexaneacetic acid)(1)-
  • argipressin, (1-mercapto-4-phenylcyclohexaneacetic acid)(1)-