Disclosing the Rich Crystal Chemistry of Lesinurad by ab Initio Laboratory X-ray Powder Diffraction Methods

Lesinurad, a uric acid reabsorption inhibitor that received Food and Drug Administration approval in 2015, is known to crystallize in three unsolvated crystal forms and in a few solvated phases. The structures of the former have been determined by state-of-the-art powder diffraction methods, highlighting significant conformational as well as supramolecular differences, resulting in hydrogen bonded centrosymmetric dimers (Form 1) or helical chains (Form 2). In the complex crystal packing in Form 3, additional one-dimensional (1D) ribbons held together by unexpected C=O center dot center dot center dot Br interactions of the halogen-bond type are found. Thermal analyses and variable-temperature powder diffraction measurements (including high temperature synchrotron X-ray diffraction experiments) provided evidence for the reversible formation of a new phase, Form 2hT, obtained upon heating above 100 degrees C powders of Form 2. Structure solution and refinement of the high-temperature phase made it possible to attribute the structural change to a 60 degrees rotation of the cyclopropyl residue, leaving unaffected the conformation of the (longer) polar branch and the supramolecular 1D helical chain arrangement found in the RT phase.