RT Journal Article
T1 Synthesis, pharmacological evaluation and docking studies of pyrrole structure-based CB 2 receptor antagonists
A1 Ragusa, Giulio
A1 Gómez Cañas, María
A1 Pazos Rodríguez, María Ruth
A1 Fernández Ruiz, José Javier
A1 García Arencibia, Moisés
A1 Murineddu, Gabriele
AB During the last years, there has been a continuous interest in the development of cannabinoid receptor ligands that may serve as therapeutic agents and/or as experimental tools. This prompted us to design and synthesize analogues of the CB2 receptor antagonist N-fenchyl-5-(4-chloro-3-methyl-phenyl)-1-(4- methyl-benzyl)-1H-pyrazole-3-carboxamide (SR144528). The structural modifications involved the bioisosteric replacement of the pyrazole ring by a pyrrole ring and variations on the amine carbamoyl substituents. Two of these compounds, the fenchyl pyrrole analogue 6 and the myrtanyl derivative 10, showed high affinity (Ki in the low nM range) and selectivity for the CB2 receptor and both resulted to be antagonists/inverse agonists in [35S]-GTPgS binding analysis and in an in vitro CB2 receptor bioassay. Cannabinoid receptor binding data of the series allowed identifying steric constraints within the CB2 binding pocket using a study of Van der Waals' volume maps. Glide docking studies revealed that all docked compounds bind in the same region of the CB2 receptor inactive state model.
PB Elsevier
SN 0223-5234
YR 2015
FD 2015
LK https://hdl.handle.net/20.500.14352/93748
UL https://hdl.handle.net/20.500.14352/93748
LA eng
NO Ragusa G, Gómez-Cañas M, Morales P, Hurst DP, Deligia F, Pazos R, Pinna GA, Fernández-Ruiz J, Goya P, Reggio PH, Jagerovic N, García-Arencibia M, Murineddu G. Synthesis, pharmacological evaluation and docking studies of pyrrole structure-based CB2 receptor antagonists. Eur J Med Chem. 2015 Aug 28;101:651-67. doi: 10.1016/j.ejmech.2015.06.057
NO Regione Autonoma della Sardegna
NO Ministerio de Economía y Competitividad (España)
NO Consejo Superior de Investigaciones Científicas
NO Comunidad de Madrid
DS Docta Complutense
RD 4 abr 2025