The cocrystal structures of four inhibitors with human MAGL were determined to confirm their binding modes and gain a structural understanding of their superior inhibitory activity (Figure ). Compared to the binding mode observed for compound 17, the benzoxazole motif on the left-hand side of the molecules is inverted in the new compounds. This flip is likely driven by additional hydrophobic interactions formed by the new substituents in this region of the MAGL binding site.