Article
Orally Active MMP-1 Sparing α-tetrahydropyranyl and α-piperidinyl Sulfone Matrix Metalloproteinase (MMP) Inhibitors with Efficacy in Cancer, Arthritis, and Cardiovascular Disease
Journal of Medicinal Chemistry
Document Type
Article
Publication Date
9-23-2010
Pages
6653–6680
Publisher Name
American Chemical Society
Disciplines
Abstract
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.
Creative Commons License
Creative Commons Attribution-Noncommercial-No Derivative Works 3.0
Copyright Statement
© 2010 American Chemical Society
Citation Information
Daniel P Becker, Thomas E. Barta, Louis J. Bedell and Terri L. Boehm. "Orally Active MMP-1 Sparing α-tetrahydropyranyl and α-piperidinyl Sulfone Matrix Metalloproteinase (MMP) Inhibitors with Efficacy in Cancer, Arthritis, and Cardiovascular Disease" Journal of Medicinal Chemistry Vol. 53 Iss. 18 (2010) Available at: http://works.bepress.com/daniel_p_becker/99/
Author Posting © American Chemical Society, 2010. This is the author's version of the work. It is posted here by permission of American Chemical Society for personal use, not for redistribution. The definitive version was published in Journal of Medicinal Chemistry, Volume 53, Issue 18, September 23, 2010. http://dx.doi.org/10.1021/jm100669j