Stereospecific Synthesis of 5-Substituted 2-Bisarylthiocyclopentane Carboxylic Acids as Specific Matrix Metalloproteinase Inhibitors

The synthesis and structure−activity relationship (SAR) studies of a series of cyclopentane carboxylic acid matrix metalloproteinase (MMP) inhibitors are described. Potent and specific MMP-2, -3, -9, -13 inhibitors were obtained by regio- and stereoselective substitutions at positions 2 and 5 on the cyclopentane ring. Compounds 2a and 2e are active in the mouse B16−F10 metastasis model and display very good pharmacokinetic parameters.