Document Type
Article
Publication Date
10-20-2005
Publication Title
Journal of Medicinal Chemistry
Volume
48
Issue
21
Pages
6713–6730
Publisher Name
American Chemical Society
Abstract
α-Piperidine-β-sulfone hydroxamate derivatives were explored that are potent for matrix metalloproteinases (MMP)-2, -9, and -13 and are sparing of MMP-1. The investigation of the β-sulfones subsequently led to the discovery of hitherto unknown α-sulfone hydroxamates that are superior to the corresponding β-sulfones in potency for target MMPs, selectivity vs MMP-1, and exposure when dosed orally. α-Piperidine-α-sulfone hydroxamate 35f (SC-276) was advanced through antitumor and antiangiogenesis assays and was selected for development. Compound 35f demonstrates excellent antitumor activity vs MX-1 breast tumor in mice when dosed orally as monotherapy or in combination with paclitaxel.
Recommended Citation
Becker, Daniel; Villamil, Clara I.; Barta, Thomas E.; and Bedell, Louis J.. Synthesis and Structure-Activity Relationships of ß- and a-Piperidine Sulphone Hydroxamic Acid Matrix Metalloproteinase Inhibitors with Oral Antitumor Efficacy. Journal of Medicinal Chemistry, 48, 21: 6713–6730, 2005. Retrieved from Loyola eCommons, Chemistry: Faculty Publications and Other Works, http://dx.doi.org/10.1021/jm0500875
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.
Copyright Statement
© 2005 American Chemical Society
Comments
Author Posting © American Chemical Society, 2005. 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 48, Issue 21, October 20, 2005. http://dx.doi.org/10.1021/jm0500875