Design and synthesis of KNT-127, a δ-opioid receptor agonist effective by systemic administration

Bioorg Med Chem Lett. 2010 Nov 1;20(21):6302-5. doi: 10.1016/j.bmcl.2010.08.083. Epub 2010 Aug 21.

Abstract

We have reported previously the novel δ-opioid agonist, SN-28, which was more potent in in vitro assays than the prototype δ-agonists, TAN-67 and SNC-80. However, when administered by subcutaneous injection, this compound showed no analgesic effect at dosages greater than 30mg/kg in the acetic acid writhing test. We speculated that SN-28 was not effective in the test because the presence of the charged ammonium groups prevented its penetration through the blood-brain barrier. On the basis of our proposal, we designed the novel δ-agonist, KNT-127, which was effective with systemic administration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetic Acid
  • Analgesics, Opioid / chemical synthesis*
  • Analgesics, Opioid / chemistry
  • Analgesics, Opioid / pharmacology*
  • Animals
  • Benzamides / pharmacology
  • Blood-Brain Barrier / drug effects
  • Indicators and Reagents
  • Injections, Spinal
  • Injections, Subcutaneous
  • Mice
  • Morphinans / chemical synthesis*
  • Morphinans / pharmacology*
  • Pain Measurement / drug effects
  • Piperazines / pharmacology
  • Quinolines / pharmacology
  • Receptors, Opioid, delta / agonists*
  • Structure-Activity Relationship

Substances

  • Analgesics, Opioid
  • Benzamides
  • Indicators and Reagents
  • KNT 127
  • Morphinans
  • Piperazines
  • Quinolines
  • Receptors, Opioid, delta
  • TAN 67
  • 4-(alpha-(4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl)-N,N-diethylbenzamide
  • Acetic Acid