| Autor: |
Becker, D. P., Villamil, C. I., Barta, T. E., Bedell, L. J., Boehm, T. L., DeCrescenzo, G. A., Freskos, J. N., Getman, D. P., Hockerman, S., Heintz, R., Howard, S. C., Li, M. H., McDonald, J. J., Carron, C. P., Funckes-Shippy, C. L., Mehta, P. P., Munie, G. E., Swearingen, C. A. |
| Zdroj: |
Journal of Medicinal Chemistry; October 2005, Vol. 48 Issue: 21 p6713-6730, 18p |
| Abstrakt: |
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. |
| Databáze: |
Supplemental Index |
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