Orally active MMP-1 sparing α-tetrahydropyranyl and α-piperidinyl sulfone matrix metalloproteinase (MMP) inhibitors with efficacy in cancer, arthritis, and cardiovascular disease

Autor: Chris P. Carron, Madeleine H. Li, Daniel P. Becker, T. Sunyer, John N. Freskos, Louis J. Bedell, Boehm Terri L, Chris L. Funckes-Shippy, Decrescenzo Gary A, Clara I. Villamil, Joseph J. McDonald, Grace E. Munie, Jeffery N. Carroll, Pramod P. Mehta, Jun Yao, Brian R. Bond, Craig Swearingen, Jennifer M. Williams, Barta Thomas E, Marcia I. Heron, Dean Welsch, Karl J. Mathis, Carol Pearcy Howard, James R. Kiefer, Susan L. Hockerman, Alan M. Easton, Ying Yu
Rok vydání: 2010
Předmět:
Zdroj: Journal of medicinal chemistry. 53(18)
ISSN: 1520-4804
Popis: α-Sulfone-α-piperidine and α-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. α-Piperidine 19v (SC-78080/SD-2590) was selected for development toward the initial indication of cancer, while α-piperidine and α-tetrahydropyranyl hydroxamates 19w (SC-77964) and 9i (SC-77774), respectively, were identified as backup compounds.
Databáze: OpenAIRE