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The ethylbenzyl and n-propylphenyl isomers exhibited a strongly reduced CB1 activity (EC50 values 100 nM; efficacy less then 40% relative to JWH-018), which is hypothesized to originate from steric hindrance in the ligand-binding pocket. None of the evaluated compounds exhibited significant biased agonism. In conclusion, the functional assays applied here allowed us to demonstrate that 5-fluorination of Cumyl-PEGACLONE is not linked to an intrinsically higher CB1 activation potential and that the ethylbenzyl and n-propylphenyl isomer
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