Thienopyrimidine Derivatives as GPR55 Receptor Antagonists: Insight into Structure-Activity Relationship

GPR55 is an orphan G-protein coupled receptor involved in various pathophysiological conditions. However, there are only a few noncannabinoid GPR55 ligands reported so far. The lack of potent and selective GPR55 ligands precludes a deep exploration of this receptor. The studies presented here focuse...

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Detalles Bibliográficos
Autores: Figuerola-Asencio, Laura, Morales, Paula, Zhao, Pingwei, Hurst, D. P., Sayed, Sommayah S., Colón, Katsuya L., Gómez-Cañas, María, Fernández-Ruiz, Javier, Croatt, Mitchell P., Reggio, Patricia H., Abood, Mary E., Jagerovic, Nadine
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/309060
Acceso en línea:http://hdl.handle.net/10261/309060
Access Level:acceso abierto
Palabra clave:GPR55, antagonist, cannabinoid, thienopyrimidine, SAR
Descripción
Sumario:GPR55 is an orphan G-protein coupled receptor involved in various pathophysiological conditions. However, there are only a few noncannabinoid GPR55 ligands reported so far. The lack of potent and selective GPR55 ligands precludes a deep exploration of this receptor. The studies presented here focused on a thienopyrimidine scaffold based on the GPR55 antagonist ML192, previously discovered by high-throughput screening. The GPR55 activities of the new synthesized compounds were assessed using β-arrestin recruitment assays in Chinese hamster ovary cells overexpressing human GPR55. Some derivatives were identified as GPR55 antagonists with functional efficacy and selectivity versus CB1 and CB2 cannabinoid receptors.

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