Structure and Thermodynamical Properties of Metformin Salicylate

The behavior under thermal conditions of the cocrystal formed by metformin and salicylic acid was studied by DSC, crystallography (single-crystal), and powder diffraction (WAXS). Metformin salicylate crystallizes in space group <i>P</i>2₁/<i>c</i>, with the salicylate anion showing a planar structure, stabilized by strong intramolecular hydrogen bonds. The more flexible metformin cations link through the oxygen atoms of salicylate, forming a dense hydrogen-bonding network. The compound exists initially as a salt, metformin salicylate, but after melting and cooling, it is transformed into a glass form that crystallizes and melts again, showing different behaviors depending on the heating rate

Novel Oxazolidinone-Based Peroxisome Proliferator Activated Receptor Agonists: Molecular Modeling, Synthesis, and Biological Evaluation

A series of new peroxisome proliferator activated receptors (PPARs) chiral ligands have been designed following the accepted three-module structure comprising a polar head, linker, and hydrophobic tail. The majority of the ligands incorporate the oxazolidinone moiety as a novel polar head, and the nature of the hydrophobic tail has also been varied. Docking studies using the crystal structure of an agonist bound to the ligand binding domain of the PPARα receptor have been performed as a tool for their design. Suitable synthetic procedures have been developed, and compounds with different stereochemistries have been prepared. Evaluation of basal and ligand-induced activity proved that several compounds showed agonist activity at the PPARα receptor, thus validating the oxazolidinone template for PPAR activity. In addition, two compounds, <b>2</b> and <b>4</b>, showed dual PPARα/PPARγ agonism and interesting food intake reduction in rats