A way to manage the thermal flexibility of ligand candidates for bioassays

An original way to manage both stereochemistry and conformational constraints in ligand candidates for bioassays is presented with reference to a group of model N,N′-tetrasubstituted o-phthalamides and thioamides. The study shows that a scale of thermal flexibility in solution can be envisaged, the divisions of which are represented by compounds sharing quite similar geometrical features. NMR spectroscopy and powder X-ray analysis were used for the physical chemical investigation. An attempt to exploit the conformational instability of a model thioamide in the medium of a bioassay was also performed.