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

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 30 mg/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.

Graphical abstractWe designed novel δ-agonists, effective in systemic administration. One of the agonists, KNT-127, is expected to be a useful tool to clarify the real pharmacological effects mediated via the δ-receptor including analgesia and addiction.Figure optionsDownload full-size imageDownload as PowerPoint slide