Phenoxyphenyl sulfone N-formylhydroxylamines (retrohydroxamates) as potent, selective, orally bioavailable matrix metalloproteinase inhibitors

…, CL Goodfellow, PA Marcotte, P Tapang…

文献索引：Wada; Holms; Curtin; Dai; Florjancic; Garland; Guo; Heyman; Stacey; Steinman; Albert; Bouska; Elmore; Goodfellow; Marcotte; Tapang; Morgan; Michaelides; Davidsen Journal of Medicinal Chemistry, 2002 , vol. 45, # 1 p. 219 - 232

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被引用次数: 102

摘要

A novel series of sulfone N-formylhydroxylamines (retrohydroxamates) have been investigated as matrix metalloproteinases (MMP) inhibitors. The substitution of the ether linkage of ABT-770 (5) with a sulfone group 13a led to a substantial increase in activity against MMP-9 but was accompanied by a loss of selectivity for inhibition of MMP-2 and-9 over MMP-1 and diminished oral exposure. Replacement of the biphenyl P1'substituent ...