Affordable Access

Synthesis and biological activity of oxytocin analogues containing conformationally-restricted residues in position 7

Authors
Journal
European Journal of Medicinal Chemistry
0223-5234
Publisher
Elsevier
Publication Date
Volume
42
Issue
6
Identifiers
DOI: 10.1016/j.ejmech.2006.12.016
Keywords
  • Oxytocin Analogues
  • α-Aminoisobutyric Acid
  • 1
  • 2
  • 3
  • 4-Tetrahydroisoquinoline-3-Carboxylic Acid
  • L-α-T-Butylglycine
  • Pipecolic Acid
  • Biological Activity
Disciplines
  • Biology
  • Pharmacology

Abstract

Abstract We report the solid-phase synthesis and some pharmacological properties of twenty oxytocin (OT) analogues. Basic modifications at position 7 (introduction of α-aminoisobutyric acid [Aib], l- or d-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid [ l/ d-Tic], l- α- t-butylglycine [Gly(Bu t )] and pipecolic acid [Pip]) were combined with d-Tyr(Et) 2, l/ d-( pEt)Phe 2, d-Tic 2, and Mpa 1 modifications and their various combinations in a total of 14 analogues. Additionally, two analogues having one more modification in position 3, i.e. Gly(Bu t ), and three analogues having glycine in position 9 substituted by d-Tic or Aib, were prepared. The analogues were tested for rat uterotonic activity in vitro, in the rat pressor assay and for binding affinity to human OT receptor. The analogue having the highest antioxytocic activity was [Mpa 1, d-Tyr(Et) 2, d-Tic 7, Aib 9]OT having pA 2 = 8.31 ± 0.19; this analogue was also selective.

There are no comments yet on this publication. Be the first to share your thoughts.