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.
Synthesis, biological evaluation and docking studies of a novel class of sulfur-bridged diazabicyclo[3.3.1]nonanes / Murineddu, G., Asproni, B., Corona, P., Gessi, S., Merighi, S., Battistello, E., Sturaro, C., Calo, G., Galeotti, N., Temml, V., Herdlinger, S., Schuster, D., Pinna, G.A.. - In: BIOORGANIC CHEMISTRY. - ISSN 0045-2068. - 102:(2020), p. 104072. [10.1016/j.bioorg.2020.104072]
Synthesis, biological evaluation and docking studies of a novel class of sulfur-bridged diazabicyclo[3.3.1]nonanes
Murineddu G.;Asproni B.;Corona P.;Pinna G. A.
2020-01-01
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
