CB2 antagonists

Iwamura and Ueda [386] described compound (611) as a CB2 selective inverse agonist in a patent application. The potential therapeutic roles of CB2 antagonists are not clearly defined at the moment, although roles in regulation of the immune system and inflammation have been widely proposed. This patent application describes that activity of compound (611) in a mouse model of asthma, in which the compound suppressed immediate and late-phase asthmatic response and airway hyper-responsiveness. 

Chen, J.Z., Wang, J., andXie,X.Q. (2007) GPCR structure-based virtual screening approach for CB2 antagonist search. Journal of Chemical Information and Modeling, 47 (4), 1626-1637. 

A -THC and other synthetic caimabinoids rehably induce hyperphagia and increase food intake in laboratory animals (61-64). These hyperphagic actions are mediated via cannabinoid CB i receptors since they are selectively blocked by the cannabinoid CBi receptor antagonist SR141716A but not with the CB2 antagonist SR 144258 (71). 

A number of synthetic compounds, completely unrelated to the structure of natural cannabinoids have been found to act as CB and/or CB2 antagonist/ inverse agonist. The most important member of this class of compounds is rimonabant (29), a diarylpyrazole derivative [57], approved for the treatment of obesity and as an aid in the cessation of cigarette smoking, but later withdrawn from the market because of the severe depression it could induce in sensitive patients. A number of structural motifs significantly different from the p3razole system have been proposed for CB2 selective antagonists, as exemplified by the quinoline derivative 30. 

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