2. Academic Validation
  3. New cannabinoid receptor antagonists as pharmacological tool

New cannabinoid receptor antagonists as pharmacological tool

  • Bioorg Med Chem. 2020 Oct 1;28(19):115672. doi: 10.1016/j.bmc.2020.115672.
Pedro González-Naranjo 1,  Concepción Pérez 1,  Rocío Girón 2,  Eva M Sánchez-Robles 2,  María I Martín-Fontelles 2,  Natalia Carrillo-López 3,  Julia Martín-Vírgala 3,  Manuel Naves 3,  Nuria E Campillo 4,  Juan A Páez 5
Affiliations

Affiliations

  • 1 Instituto de Química Médica (CSIC), Juan de la Cierva 3, 28006 Madrid, Spain.
  • 2 Área de Farmacología, Nutrición y Bromatología, Unidad Asociada al IQM y al CIAL (CSIC), Departamento de C.C. Básicas de la Salud, Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos, Avda. Atenas s/n, 28922 Alcorcón, Spain.
  • 3 U.G.C de Metabolismo Óseo, RedinREN del ISC III, Hospital Universitario Central de Asturias, Instituto de Investigaciones Sanitarias del Principado de Asturias, Edificio FINBA, Planta primera F1.1 (Aula 14), Avenida de Roma s/n, 33011 Oviedo, Spain.
  • 4 Centro de Investigaciones Biológicas Margarita Salas (CSIC), Ramiro de Maeztu 9, 28040 Madrid, Spain. Electronic address: [email protected].
  • 5 Instituto de Química Médica (CSIC), Juan de la Cierva 3, 28006 Madrid, Spain. Electronic address: [email protected].
PMID: 32912440 DOI: 10.1016/j.bmc.2020.115672
Abstract

Synthesis and pharmacological evaluation of a new series of Cannabinoid Receptor antagonists of indazole ether derivatives have been performed. Pharmacological evaluation includes radioligand binding assays with [3H]-CP55940 for CB1 and CB2 receptors and functional activity for cannabinoid receptors on isolated tissue. In addition, functional activity of the two synthetic cannabinoids antagonists 18 (PGN36) and 17 (PGN38) were carried out in the osteoblastic cell line MC3T3-E1 that is able to express CB2R upon osteogenic conditions. Both antagonists abolished the increase in collagen type I gene expression by the well-known inducer of bone activity, the HU308 agonist. The results of pharmacological tests have revealed that four of these derivatives behave as CB2R cannabinoid antagonists. In particular, the compounds 17 (PGN38) and 18 (PGN36) highlight as promising candidates as pharmacological tools.

Keywords

Antagonist; Bone disease; Cannabinoid receptors; Indazole ether; Pharmacological tool.

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