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Orally active MMP-1 sparing alpha-tetrahydropyranyl and alpha-piperidinyl Sulfone matrix metalloproteinase (MMP) inhibitors with efficacy in cancer, arthritis, and cardiovascular disease
alpha-Sulfone-alpha-piperidine and alpha-tetrahydropyranyl hydroxamates were explored that are potent inhibitors of MMPs-2,-9, and-13 that spare MMP-1, with oral efficacy in inhibiting tumor growth in mice and left-ventricular hypertrophy in rats and in the bovine cartilage degradation ex vivo explant system. alpha-Piperidine 19v (SC-78080/SD-2590) was selected for development toward the initial indication of cancer, while alpha-piperidine and alpha-tetrahydropyranyl hydroxamates 19w (SC-77964) and 9i (SC-77774), respectively, were identified as backup compounds.
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