Radioligand binding results of key compounds 61, 61a, 61b.

Concentration-dependent inhibition of specific [3H]CP55,940 binding by 61 (▪) at membrane preparations of CHO cells expressing (A) human CB1, or (B) human CB2 receptors, respectively (Ki CB1∶0.145 µM, CB2∶0.0294 µM). The biphenol 61 is substituted with two alkyl residues, a propyl residue at one side and a hexyl chain at the other side of the biphenylic core. Each alkyl side chain is located in the para-position of one of the phenolic hydroxyl groups. Substitution of the hydroxyl group in the para-position of the propyl residue (61a (▾)) resulted in a remarkable increase in (A) CB1 receptor affinity (Ki: 0.00957 µM), while (B) CB2 receptor affinity was barely affected (Ki: 0.0238 µM) compared to the parent compound 61. An introduction of a methoxy group in para-position of the hexyl side chain (61b (•)) had different effects: (A) 61b displayed a moderately decreased CB1 receptor affinity (Ki: 0.313 µM) and (B) a drastical loss in CB2 receptor affinity (Ki: 0.281 µM) compared to 61. Data points represent means ± SEM of three independent experiments, performed in duplicates.