1. Synthesis, biological evaluation and docking studies of a novel class of sulfur-bridged diazabicyclo[3.3.1]nonanes
- Author
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Stefania Gessi, Gérard Aimé Pinna, Veronika Temml, Girolamo Calo, Sonja Herdlinger, Enrica Battistello, Paola Corona, Nicoletta Galeotti, Daniela Schuster, Battistina Asproni, Stefania Merighi, Gabriele Murineddu, and Chiara Sturaro
- Subjects
9-diazabicyclo[3.3.1]nonanes ,Binding affinities ,Opiod receptors ,μ receptor ,Stereochemistry ,chemistry.chemical_element ,01 natural sciences ,Biochemistry ,NO ,3-thia-7,9-diazabicyclo[3.3.1]nonanes, Opiod receptors, Binding affinities, Antinociceptive activity, Molecular docking ,Structure-Activity Relationship ,chemistry.chemical_compound ,Alkanes ,Drug Discovery ,Humans ,Receptor ,Molecular Biology ,Biological evaluation ,Molecular Structure ,010405 organic chemistry ,Antinociceptive activity ,Organic Chemistry ,Sulfur ,3-thia-7 ,Molecular docking ,0104 chemical sciences ,Molecular Docking Simulation ,010404 medicinal & biomolecular chemistry ,chemistry ,Docking (molecular) ,Thermal pain ,Nonane ,Selectivity - Abstract
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 (Ki = 85 nM) and selectivity (Ki μ/δ = 58.8, Ki 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.
- Published
- 2020