Discovery of a benzimidazole series of ADAMTS-5 (aggrecanase-2) inhibitors by scaffold hopping

Abstract We describe a medicinal chemistry approach to generate a series of benzimidazoles bearing thiazolidin-4-one using scaffold hopping from thiazole 1 , our previously described thiazole. Our goal was to discover a potent and permeable small-molecule ADAMTS-5 inhibitor. The results suggest that small compound 22 shows promise as a potent small-molecule ADAMTS-5 inhibitor with good permeability.