Opioid analgesics are clinically used to relieve severe pain in acute postoperative and cancer pain, and also in the long term in chronic pain. The analgesic action is mediated by μ-, δ-, and κ-receptors, but currently, with few exceptions for k-agonists, μ-agonists are the only ones used in therapy. Previously synthesized compounds with diazotricyclodecane cores (DTDs) have shown their effectiveness in binding opioid receptors. Fourteen novel diazatricyclodecanes belonging to the 9-propionyl-10-substituted-9,10-diazatricyclo[4.2.1.12,5]decane (compounds 20-23, 53, 57 and 59) and 2-propionyl-7-substituted-2,7-diazatricyclo[4.4.0.03,8]decane (compounds 24-27, 54, 58 and 60) series, respectively, have been synthesized and their ability to bind to the opioid μ-, δ- and κ-receptors was evaluated. Five of these derivatives, compounds 20, 21, 24, 26 and 53, showed μ-affinity in the nanomolar range with a negligible affinity towards δ- and κ-receptors and high μ-receptor selectivity. The synthesized compounds showed μ-receptor selectivity higher than those of previously reported methylarylcinnamyl analogs.

Biological Effects on μ-Receptors Affinity and Selectivity of Arylpropenyl Chain Structural Modification on Diazatricyclodecane Derivatives. / Piras, Sandra; Murineddu, Gabriele; Loriga2, Giovanni; Carta, Antonio; Battistello, Enrica; Merighi, Stefania; Gessi, Stefania; Corona, Paola; Asproni, Battistina; Ibba, Roberta; Temml, Veronika; Schuster, Daniela; Pinna, Gerard Aime. - In: MOLECULES. - ISSN 1420-3049. - 26(18):5448:18(2021), p. 5448. [10.3390/molecules26185448]

Biological Effects on μ-Receptors Affinity and Selectivity of Arylpropenyl Chain Structural Modification on Diazatricyclodecane Derivatives. .

Sandra Piras
;
Gabriele Murineddu;Antonio Carta;Paola Corona;Battistina Asproni;Gérard Aimè Pinna
2021

Abstract

Opioid analgesics are clinically used to relieve severe pain in acute postoperative and cancer pain, and also in the long term in chronic pain. The analgesic action is mediated by μ-, δ-, and κ-receptors, but currently, with few exceptions for k-agonists, μ-agonists are the only ones used in therapy. Previously synthesized compounds with diazotricyclodecane cores (DTDs) have shown their effectiveness in binding opioid receptors. Fourteen novel diazatricyclodecanes belonging to the 9-propionyl-10-substituted-9,10-diazatricyclo[4.2.1.12,5]decane (compounds 20-23, 53, 57 and 59) and 2-propionyl-7-substituted-2,7-diazatricyclo[4.4.0.03,8]decane (compounds 24-27, 54, 58 and 60) series, respectively, have been synthesized and their ability to bind to the opioid μ-, δ- and κ-receptors was evaluated. Five of these derivatives, compounds 20, 21, 24, 26 and 53, showed μ-affinity in the nanomolar range with a negligible affinity towards δ- and κ-receptors and high μ-receptor selectivity. The synthesized compounds showed μ-receptor selectivity higher than those of previously reported methylarylcinnamyl analogs.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11388/255979
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