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Intracranial Pharmacotherapy and Pain Assays in Rodents
Published on: April 9, 2019
Propionamide Derivatives as Dual μ-Opioid Receptor Agonists and σ1 Receptor Antagonists for the Treatment of Pain
Mónica García1, Virginia Llorente1, Lourdes Garriga1
1ESTEVE Pharmaceuticals, Torre Esteve, Passeig de la Zona Franca, 109, Barcelona 08038, Spain.
Abstract:
A new series of propionamide derivatives was developed as dual μ-opioid receptor agonists and σ1 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, 18g, 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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