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]
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Titolo: | Biological Effects on μ-Receptors Affinity and Selectivity of Arylpropenyl Chain Structural Modification on Diazatricyclodecane Derivatives. . | |
Autori: | ||
Data di pubblicazione: | 2021 | |
Rivista: | ||
Citazione: | 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] | |
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. | |
Handle: | http://hdl.handle.net/11388/255979 | |
Appare nelle tipologie: | 1.1 Articolo in rivista |