Article
MMP-13 Selective α-sulfone Hydroxamates: a Survey of P1' Heterocyclic Amide Isosteres
Bioorganic & Medicinal Chemistry Letters
Document Type
Article
Publication Date
5-15-2011
Pages
2820-2822
Publisher Name
Elsevier
Disciplines
Abstract
Seeking compounds preferentially potent and selective for MMP-13, we reported in the preceding Letter on a series of hydroxamic acids with a flexible benzamide tail groups.(1a) Here, we replace the amide moiety with non-hydrolyzable heterocycles in an effort to improve half-life. We identify a hydroxamate tetrazole 4e that spares MMP-1 and -14, shows >400-fold selectivity versus MMP-8 and >600-fold selectivity versus MMP-2, and has a 4.8 h half-life in rats. X-ray data (1.9 Å) for tetrazole 4c is presented.
Creative Commons License
Creative Commons Attribution-Noncommercial-No Derivative Works 3.0
Copyright Statement
© 2011 Elsevier
Citation Information
Thomas E. Barta, Daniel P. Becker, Louis J. Bedell and Alan M. Easton. "MMP-13 Selective α-sulfone Hydroxamates: a Survey of P1' Heterocyclic Amide Isosteres" Bioorganic & Medicinal Chemistry Letters Vol. 21 Iss. 10 (2011) Available at: http://works.bepress.com/daniel_p_becker/98/
Author Posting © Elsevier, 2011. This is the author's version of the work. It is posted here by permission of Elsevier for personal use, not for redistribution. The definitive version was published in Bioorganic & Medicinal Chemistry Letters, Volume 21, Issue 10, May 15, 2011. http://dx.doi.org/10.1016/j.bmcl.2011.03.099