Author/Authors :
Lawrence A. Reiter، نويسنده , , Peter G. Mitchell، نويسنده , , Gary J. Martinelli، نويسنده , , Lori L. Lopresti-Morrow، نويسنده , , Sue A. Yocum، نويسنده , , James D. Eskra، نويسنده ,
Abstract :
Phosphinic acid-based inhibitors of MMP-13 have been investigated with the aim of identifying potent inhibitors with high selectivity versus MMP-1. Independent variation of the substituents on a P1′ phenethyl group and a P2 benzyl group improved potencies in both cases around 3-fold over the unsubstituted parent. Combining improved P1′ and P2 groups into a single molecule gave an inhibitor with a 4.5 nM IC50 against MMP-13 and which is 270-fold selective over MMP-1.
