Document Type

Article

Publication Date

10-20-2005

Publication Title

Journal of Medicinal Chemistry

Volume

48

Issue

21

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.

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

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