The docking scores for selected poses (sorted by docking score) of the reference compounds and the five compounds selected for synthesis (series 1, compounds 1a to 1e) are shown in Tabs S2 and S3 (SI). In the pose with the phenyl tail of 1a in subpocket C, one halogen bond is formed between the meta-Cl of the 3,4-dichlorophenyl moiety and the backbone carbonyl oxygen of Trp221 (Fig. ). In the pose with the phenyl tail occupying subpocket D, the placement of the tail is similar to that of V (Fig. and, respectively). -45.2 kcal/mol; electrostatic : -6.5 vs. -8.1 kcal/mol, respectively, Tab. S2, SI). The internal energy is however significantly more favorable for the trans than the cis configuration (6.6 vs. 13.7 kcal/mol, Tab. S2, SI). In the trans pose (pose 1, Fig. ), the N-cyclopropyl is in contact with the side chains of Met213 and Trp221, while in the cis configuration, it contacts the side chain of Cys168 (pose 2, Fig. ).