Figure 3.

Docking poses of representative pyrrole-based CB₁R ligand 14 and DEG probe precursor 22b in the CB₁R inactive state (light gray, docked in PDB ID: 5TGZ, X-ray diffraction, 2.80 Å).⁵⁶ (A) Docking pose of novel DEG ethyl ester ligand 14 (bright yellow) located in the binding pocket of CB₁R with the ethyl ester group pointing toward the N-terminal site. (B) Linker installation on 14 via the carboxy-terminal amide bond of DEG is a reasonable strategy based on the docking structures. (C) DEG probe precursor 22b with n = 2 (orange). (D) Linker reaches the CB₁R extracellular site through trans-membrane helices (TM) 1 and 2. For docking poses of 15–19, 23b, and 24–27 and a detailed description of the docking studies, see Supporting Information.