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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Hauptverfasser: | , , , , , , , , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
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Zusammenfassung: | 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. |
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ISSN: | 0022-2623 1520-4804 |
DOI: | 10.1021/acs.jmedchem.1c00417 |