| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1399014 | European Journal of Medicinal Chemistry | 2013 | 14 Pages |
•Synthesis of conformationally restricted analogs of δ-agonist SNC-80 was reported.•High δ affinity and selectivity were observed for most of the compounds synthesized.•Preliminary in vivo assays confirmed antinociceptive activity of 1Aa in tail flick test.
Considering the interesting pharmacological profile of the delta (δ) selective opioid agonist compound SNC-80, conformationally constrained analogs containing two diazatricyclodecane ring systems in place of dimethylpiperazine core motif were synthesized.The compounds showed subnanomolar or low nanomolar δ opioid receptor binding affinity. Depending upon the substituents on the diazatricyclodecane ring, these compounds displayed varying selectivity for δ opioid receptor over μ and κ receptors.Amongst the novel compounds, 1Aa showed the more interesting biological profile, with higher δ affinity and selectivity compared to SNC-80. The δ receptor agonist profile and antinociceptive activity of 1Aa were confirmed using ex-vivo (isolated mouse vas deferens) and in vivo (tail flick) assays.
Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slide
