Structure–activity study on a series of α-glutamic acid scaffold based compounds as new ADAMTS inhibitors

A series of α-glutamic acid scaffold based 4-(benzamido)-4-(1,3,4-oxadiazol-2-yl) butanoic acids were designed and synthesized as new ADAMTS inhibitors. The compounds dose-dependently inhibited the enzymatic activities of ADAMTS-4 and ADAMTS-5. One of the most active compound 2h potently inhibited ADAMTS-4 and ADAMTS-5 with IC50 values of 1.2 and 0.8 μM, respectively. These inhibitors may serve as new lead compounds for further development of therapeutics to treat osteoarthritis.

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