Synthesis and biological evaluation of novel delta (未) opioid receptor ligands with diazatricyclodecane skeletons
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- 作者：Giovanni Loriga ; Paolo Lazzari ; Stefania Ruiu ; Giorgio Marchese ; Ilaria Manca ; Gian Luca Casu ; Christian Dess矛 ; G茅rard Aim猫 Pinna ; Battistina Asproni ; Gabriele Murineddu
- 关键词：未-Agonist SNC-80 ; 未-Opioid receptor ligands ; 9 ; 10-Diazatricyclo[4.2.1.12 ; 5]decane ; 2 ; 7-Diazatricyclo[4.4.0.03 ; 8]decane ; Binding assays ; Antinociceptive activity
- 刊名：European Journal of Medicinal Chemistry
- 出版年：November, 2013
- 年：2013
- 卷：69
- 期：Complete
- 页码：413-426
- 全文大小：906 K
文摘
Considering the interesting pharmacological profile of the delta (未) 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 未 opioid receptor binding affinity. Depending upon the substituents on the diazatricyclodecane ring, these compounds displayed varying selectivity for 未 opioid receptor over 渭 and 魏 receptors.
Amongst the novel compounds, boldFont">1Aa showed the more interesting biological profile, with higher 未 affinity and selectivity compared to SNC-80. The 未 receptor agonist profile and antinociceptive activity of boldFont">1Aa were confirmed using ex-vivo (isolated mouse vas deferens) and in聽vivo (tail flick) assays.