Bicyclic cannabinoids ligands

The benzopyran ring is not essential for activity. The pyran oxygen can be substituted by nitrogen or can be eliminated in open-ring mono- or bisphenolic compounds. The recently developed CB2-selective ligand HU-308 (5) is an example of such a bicyclic cannabinoid (Hanus et al., 1999). 

The recently introduced ligand HU-308 (28, Fig. 7), which has the opposite absolute configuration from all other CC and NCC analogs, is another example of bicyclic cannabinoid receptor ligands (Hanus et al. 1999) and exhibits a high degree of CB2 selectivity. 

The cannabinoid ligand can be classified according to Ooms et al [43] into six groups i) classical, ii) nonclassical, iii) bicyclic, iv) aminoalkylindoles, v) endocannabinoid analogues, vi) diarylpyrazoles. Ooms et al [43] studied the pharmacophore of 3-alkyl-5-arylimidazolidinediones as a new CBi cannabinoid receptor. Thomas et al [44] have studied SAR data on a series of 1,5-diphenylpyrazoles proposing a pharmacophoric alignment of these compounds with THC... 

From a previous medicinal chemistry campaign, novel substituted benzene sulfonamides were identified as selective cannabinoid CB2 receptor ligands. In order to improve upon the selectivity of these compounds, the central benzene template was modified to accommodate a more lipophilic bicyclic system. The synthesis, SAR and in vivo efficacy of this novel series of CB2 ligands will be presented. 

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