This design is highly conservative in that it is an isosteric modification [nX2->cH] of x10324 and a docking has not provided. Only one of the 2-connected nitrogen atoms of the triazole ring of x10324 appears to accept a hydrogen bond from the protein. The nitrogen atom that does not accept a hydrogen bond in the protein-ligand complex is, therefore, not ‘compensated’ for its ‘lost’ solvation when x10324 binds which imposes an energetic penalty on binding. Replacement of this nitrogen with aromatic CH would be expected to both reduce the desolvation penalty and increase the hydrogen bond basicity of the remaining hydrogen bond acceptor. For modelling, I’ve used the configuration (R) corresponding to the ligand in the x10324 crystal structure for the design although an assay result for the racemate would also provide useful information for decision-making.