Figure 3.

Superposition between the lowest emodel binding mode of (S)-piperazinoarylamides: (a) 19, 20 and 21 depicted as yellow, purple and dark-green sticks, respectively; (b) 25 and 26 dysplayed as brown and violet sticks, respectively. rFAAH key residues involved in ligand interactions are displayed as lines coloured relatively as the interacting ligand. Hydrogen bond interactions and T-shaped π-π stacking interaction detected by Maestro 11.1 are shown as dashed black lines. Globally, the substitution of a chorine atom to the phenyl ring (compound 19) allows an Hbond interaction with Cys269. The addition of a one more methyl group on the aromatic ring (amide 26) does not affect the binding mode of the two ligands, except for the phenyl ring itself that in the case of amide 26 is slightly oriented toward the Phe381 residue engaging one T-shape π-π stacking interaction.