Propionamide Derivatives as Dual μ-Opioid Receptor Agonists and σ 1 Receptor Antagonists for the Treatment of Pain
A new series of propionamide derivatives was developed as dual μ-opioid receptor agonists and σ receptor antagonists. Modification of a high-throughput screening hit originated a series of piperazinylcycloalkylmethyl propionamides, which were explored to overcome the challenge of achieving balanced...
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| Veröffentlicht in: | Journal of medicinal chemistry 2021-07, Vol.64 (14), p.10139-10154 |
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| container_issue | 14 |
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| container_title | Journal of medicinal chemistry |
| container_volume | 64 |
| creator | García, Mónica Llorente, Virginia Garriga, Lourdes Christmann, Ute Rodríguez-Escrich, Sergi Virgili, Marina Fernández, Begoña Bordas, Magda Ayet, Eva Burgueño, Javier Pujol, Marta Dordal, Albert Portillo-Salido, Enrique Gris, Georgia Vela, José Miguel Almansa, Carmen |
| description | A new series of propionamide derivatives was developed as dual μ-opioid receptor agonists and σ
receptor antagonists. Modification of a high-throughput screening hit originated a series of piperazinylcycloalkylmethyl propionamides, which were explored to overcome the challenge of achieving balanced dual activity and convenient drug-like properties. The lead compound identified,
, showed good analgesic effects in several animal models of both acute (paw pressure) and chronic (partial sciatic nerve ligation) pain, with reduced gastrointestinal effects in comparison with oxycodone. |
| doi_str_mv | 10.1021/acs.jmedchem.1c00417 |
| format | Article |
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| ispartof | Journal of medicinal chemistry, 2021-07, Vol.64 (14), p.10139-10154 |
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| source | MEDLINE; American Chemical Society Journals |
| subjects | Amides - chemical synthesis Amides - chemistry Amides - pharmacology Analgesics, Opioid - chemical synthesis Analgesics, Opioid - chemistry Analgesics, Opioid - pharmacology Animals Dose-Response Relationship, Drug Humans Mice Molecular Structure Narcotic Antagonists - chemical synthesis Narcotic Antagonists - chemistry Narcotic Antagonists - pharmacology Pain - drug therapy Receptors, Opioid, mu - agonists Receptors, sigma - antagonists & inhibitors Sigma-1 Receptor Structure-Activity Relationship |
| title | Propionamide Derivatives as Dual μ-Opioid Receptor Agonists and σ 1 Receptor Antagonists for the Treatment of Pain |
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