Development of Quinoline-2,4(1H,3H)-diones as Potent and Selective Ligands of the Cannabinoid Type 2 Receptor.
Basic Information
ID: ALA3588836
Journal: J Med Chem
Title: Development of Quinoline-2,4(1H,3H)-diones as Potent and Selective Ligands of the Cannabinoid Type 2 Receptor.
Authors: Han S, Zhang FF, Qian HY, Chen LL, Pu JB, Xie X, Chen JZ.
Abstract: The cannabinoid type 2 receptors (CB2Rs) play crucial roles in inflammatory diseases. There has been considerable interest in developing potent and selective ligands for CB2R. In this study, quinoline-2,4(1H,3H)-dione analogs have been designed, synthesized, and evaluated for their potencies and binding properties toward the cannabinoid type 1 receptor (CB1R) and CB2R. C5- or C8-substituted quinoline-2,4(1H,3H)-diones demonstrate CB2R agonist activity, while the C6- or C7-substituted analogs are antagonists of CB2R. In addition, oral administration of 21 dose-dependently alleviates the clinical symptoms of experimental autoimmune encephalomyelitis in a mouse model of multiple sclerosis and protects the central nervous system from immune damage. Furthermore, the interaction modes predicted by docking simulations and the 3D-QSAR model generated with CoMFA may offer guidance for further design and modification of CB2R modulators.
CiteXplore: 26151231
DOI: 10.1021/acs.jmedchem.5b00227
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