Synthesis, biological evaluation and docking studies of a novel class of sulfur-bridged diazabicyclo[3.3.1]nonanes.,Bioorganic Chemistry

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Synthesis, biological evaluation and docking studies of a novel class of sulfur-bridged diazabicyclo[3.3.1]nonanes.
Bioorganic Chemistry ( IF 4.5 ) Pub Date : 2020-07-06 , DOI: 10.1016/j.bioorg.2020.104072
Gabriele Murineddu ₁ , Battistina Asproni ₁ , Paola Corona ₁ , Stefania Gessi ₂ , Stefania Merighi ₂ , Enrica Battistello ₂ , Chiara Sturaro ₃ , Girolamo Calò ₃ , Nicoletta Galeotti ₄ , Veronika Temml ₅ , Sonja Herdlinger ₆ , Daniela Schuster ₇ , Gerard A Pinna ₁

Affiliation

A small library of 3-thia-7,9-diazabicyclo[3.3.1]nonanes was synthesized and their opioid receptors affinity and selectivity evaluated. Among these novel sulfur-bridged compounds, the (E) 9-[3′-(3-chlorophenyl)-but-2′-en-1′-yl]-7-propionyl-3-thia-7,9-diazabicyclo[3.3.1]nonane 2i emerged as the derivative with the highest μ receptor affinity (K_i = 85 nM) and selectivity (K_i μ/δ = 58.8, K_i μ/κ > 117.6). The antinociceptive activity of 2i was also evaluated in acute thermal pain. Docking studies disclosed the specific pattern of interactions of these derivatives.

中文翻译：

一类新型的硫桥二氮杂双环[3.3.1]壬烷的合成，生物学评价和对接研究。

合成了3-thia-7,9-diazabicyclo [3.3.1]壬烷的小文库，并评估了其阿片受体的亲和力和选择性。在这些新颖的硫桥化合物中，（E）9- [3'-（3-氯苯基）-but-2'-en-1'-基] -7-丙酰基-3-thia-7,9-二氮杂双环[3.3.1]壬烷2I成为该衍生物具有最高μ受体的亲和力（ķ_我 = 85 nM）的和选择性（ķ_我μ/ δ = 58.8，ķ_我μ/κ> 117.6）。在急性热痛中还评估了2i的抗伤害感受活性。对接研究揭示了这些衍生物相互作用的具体模式。

更新日期：2020-07-18

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