Journal of Medicinal Chemistry
American Chemical Society
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.
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: , 2005. Retrieved from Loyola eCommons, Chemistry: Faculty Publications and Other Works, http://dx.doi.org/10.1021/jm0500875
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