Figure 2.

Starting point for fragment growing. (A) Cocrystal structure of 1 with sEH hydrolase domain (PDB code: 4Y2T). (B) Proposed binding mode of 1 in complex with LTA4H, based on cocrystal structure of a similar fragment (PDB code: 3CHO). 1 is shown as orange sticks, the molecular surface of the binding site is colored by lipophilicity (green: lipophilic; magenta: hydrophilic), and a gray dashed circle indicates an unoccupied space in the binding site. (C) Fragment growing strategy toward amides 4a–k. Red arrows indicate H-bond acceptor, and blue arrows indicate H-bond donor capabilities of the hydroxyl moiety, which is bioisosterically replaced by the secondary amide.