Figure 15.

Example of cooperativity between two ligand chlorine atoms in a DPP-IV inhibitor series.(9) Adding both ortho- and para-Cl atoms to the 6-phenyl ring reduces the IC₅₀ against the target 8-fold more than extrapolated from the IC₅₀ values of the two single-Cl substituted and the unsubstituted analogues. The “cp pairs” list gives the predicted cooperative pairs, and the atom labels in the binding site view denote the atoms involved. An LPL_l path of length of 5 connecting the two chlorine atoms involved in cooperativity is displayed (PDB code 1rwq).