Orally active MMP-1 sparing alpha-tetrahydropyranyl and alpha-piperidinyl sulfone matrix metalloproteinase (MMP) inhibitors with efficacy in cancer, arthritis, and cardiovascular disease.
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Becker DP, Barta TE, Bedell LJ, Boehm TL, Bond BR, Carroll J, Carron CP, Decrescenzo GA, Easton AM, Freskos JN, Funckes-Shippy CL, Heron M, Hockerman S, Howard CP, Kiefer JR, Li MH, Mathis KJ, McDonald JJ, Mehta PP, Munie GE, Sunyer T, Swearingen CA, Villamil CI, Welsch D, Williams JM, Yu Y, Yao J
Orally active MMP-1 sparing alpha-tetrahydropyranyl and alpha-piperidinyl sulfone matrix metalloproteinase (MMP) inhibitors with efficacy in cancer, arthritis, and cardiovascular disease.
J Med Chem. 2010 Sep 23;53(18):6653-80. doi: 10.1021/jm100669j.
- PubMed ID
- 20726512 [ View in PubMed]
- Abstract
alpha-Sulfone-alpha-piperidine and alpha-tetrahydropyranyl hydroxamates were explored that are potent inhibitors of MMP's-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.