The two designs in this submission are isomers (1,2,4-oxadiazoles) of the 1,3,4-oxadiazole PET-UNK-37251634-3 and each design has also been submitted as a racemate. 1,2,4-Oxadiazoles are expected to be more lipophilic (see https://doi.org/10.1021/jm2013248 ) than their 1,3,4-oxadiazole isomers and this reflects differences in the hydrogen bond basicity (see https://doi.org/10.1021/acs.jmedchem.5b01946 ). My recommendation would be to first synthesize the ester PET-UNK-c7ac4d9e-1 (it should be as accessible as the amide EDJ-MED-015fb6b4-2) before making a decision which (if any) synthesize oxadiazoles should be synthesized.
Protein-ligand complexes (P1090 A chain) were energy-minimized using Szybki (MMFF94S) fixing the coordinates of the amide nitrogen and oxygen. The PDB file associated with this submission contains the following:  P0601 protein structure  P1090 A chain crystallographic ligand (MAT-POS-4223bc15-23) [3-4] Binding modes predicted for Designs 1 -2.