Figure 2.

Upper panels: Selection of the aromatic ring. Docking pose of (A) thiophene derivative 13 (cyan carbon atoms) and (B) benzene derivative 16 (salmon carbon atoms) at the hP2Y₁₄R. Both the thiophene and the benzene rings establish an additional π-cation interaction with Arg274^7.32 (dark green dashed lines). Lower panel: Selection of the optimal spacer between the aromatic and amine functions. Docking poses of derivatives bearing a spacer of three methylene groups and a (C) terminal primary amine (compound 7, light blue carbon atoms) or (D) a hydroxyl group (dark green carbon atoms) at the hP2Y₁₄R. Side chains of residues important for ligand recognition are reported as sticks (grey carbon atoms). H-bonds, salt bridges, and π-π stacking interactions are pictured as orange, magenta, and cyan dashed lines, respectively. Nonpolar hydrogen atoms are omitted.