New Pyridone-Based Derivatives as Cannabinoid Receptor Type 2 Agonists

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dc.contributor.authorFaundez Parraguez, Manuel
dc.contributor.authorAlarcon Miranda, Carlos
dc.contributor.authorCho, Young Hwa
dc.contributor.authorPessoa Mahana, Hernan
dc.contributor.authorGallardo Garrido, Carlos
dc.contributor.authorChung, Hery
dc.contributor.authorFaundez, Mario
dc.contributor.authorPessoa Mahana, David
dc.date.accessioned2024-01-10T14:22:57Z
dc.date.available2024-01-10T14:22:57Z
dc.date.issued2021
dc.description.abstractThe activation of the human cannabinoid receptor type II (CB2R) is known to mediate analgesic and anti-inflammatory processes without the central adverse effects related to cannabinoid receptor type I (CB1R). In this work we describe the synthesis and evaluation of a novel series of N-aryl-2-pyridone-3-carboxamide derivatives tested as human cannabinoid receptor type II (CB2R) agonists. Different cycloalkanes linked to the N-aryl pyridone by an amide group displayed CB2R agonist activity as determined by intracellular [cAMP] levels. The most promising compound 8d exhibited a non-toxic profile and similar potency (EC50 = 112 nM) to endogenous agonists Anandamide (AEA) and 2-Arachidonoylglycerol (2-AG) providing new information for the development of small molecules activating CB2R. Molecular docking studies showed a binding pose consistent with two structurally different agonists WIN-55212-2 and AM12033 and suggested structural requirements on the pyridone substituents that can satisfy the orthosteric pocket and induce an agonist response. Our results provide additional evidence to support the 2-pyridone ring as a suitable scaffold for the design of CB2R agonists and represent a starting point for further optimization and development of novel compounds for the treatment of pain and inflammation.</p>
dc.description.funderPontificia Universidad Catolica de Chile
dc.description.funderPontificia Universidad Catolica de Chile FONDEQUIP
dc.description.funderAgencia Nacional de Investigacion y Desarrollo (ANID) FONDECYT
dc.description.funderPontificia Universidad Catolica de Chile DIPOG
dc.fechaingreso.objetodigital2024-05-23
dc.format.extent15 páginas
dc.fuente.origenWOS
dc.identifier.doi10.3390/ijms222011212
dc.identifier.eissn1422-0067
dc.identifier.pubmedidMEDLINE:34681877
dc.identifier.urihttps://doi.org/10.3390/ijms222011212
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/80023
dc.identifier.wosidWOS:000715456600001
dc.information.autorucFacultad de Química y de Farmacia; Faundez Parraguez, Manuel Ignacio; S/I; 1058412
dc.issue.numero20
dc.language.isoen
dc.nota.accesoContenido completo
dc.publisherMDPI
dc.revistaINTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
dc.rightsacceso abierto
dc.subjectcannabinoids
dc.subject2-pyridone
dc.subjectsynthesis
dc.subjectCB2R agonists
dc.subjectENDOCANNABINOID SYSTEM
dc.subjectSELECTIVE LIGANDS
dc.subjectCB2 RECEPTOR
dc.subjectIDENTIFICATION
dc.subjectHETEROCYCLES
dc.subjectDESIGN
dc.subjectPOTENT
dc.subjectDRUGS
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleNew Pyridone-Based Derivatives as Cannabinoid Receptor Type 2 Agonists
dc.typeartículo
dc.volumen22
sipa.codpersvinculados1058412
sipa.indexWOS
sipa.trazabilidadCarga SIPA;09-01-2024
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