Chroman-4-one and chromone based somatostatin β-turn mimetics

Eur J Med Chem. 2016 May 23:114:59-64. doi: 10.1016/j.ejmech.2016.02.046. Epub 2016 Feb 21.

Abstract

A scaffold approach has been used to develop somatostatin β-turn mimetics based on chroman-4-one and chromone ring systems. Such derivatives could adopt conformations resembling type II or type II' β-turns. Side chain equivalents of the crucial Trp8 and Lys9 in somatostatin were introduced in the 2- and 8-positions of the scaffolds using efficient reactions. Interestingly, this proof-of-concept study shows that 4 and 9 have Ki-values in the low μM range when evaluated for their affinity for the sst2 and sst4 receptors.

Keywords: Chroman-4-one; Chromone; Peptidomimetics; Somatostatin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomimetic Materials / chemistry
  • Biomimetic Materials / pharmacology*
  • Chromans / chemistry
  • Chromans / pharmacology*
  • Chromones / chemistry
  • Chromones / pharmacology*
  • Dose-Response Relationship, Drug
  • Humans
  • Ligands
  • Models, Molecular
  • Molecular Structure
  • Receptors, Somatostatin / agonists*
  • Somatostatin / chemistry*
  • Somatostatin / pharmacology*
  • Structure-Activity Relationship

Substances

  • Chromans
  • Chromones
  • Ligands
  • Receptors, Somatostatin
  • SSTR2 protein, human
  • somatostatin receptor subtype-4
  • Somatostatin