Inhibition of MMP-1 and MMP-13 with phosphinic acids that exploit binding in the S2 pocket
1999
Abstract Through the use of empirical and computational methods, phosphinate-based inhibitors of MMP-1 and MMP-13 that bind into the S 2 pocket of these enzymes were designed. The synthesis and testing of 2 suggested that binding was occurring as hypothesized. Structure determination of a co-crystal of 2 bound to the catalytic domain of MMP-1 confirmed the binding mode. Substituents binding into S 2 , S 1′ , S 2′ and S 3′ , were optimized yielding compounds with low double-digit nM IC 50 's against these enzymes.
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