Synthesis and structure-activity relationships of β-and α-piperidine sulfone hydroxamic acid matrix metalloproteinase inhibitors with oral antitumor efficacy

…, TL Boehm, GA DeCrescenzo, JN Freskos…

Index: Becker, Daniel P.; Villamil, Clara I.; Barta, Thomas E.; Bedell, Louis J.; Boehm, Terri L.; DeCrescenzo, Gary A.; Freskos, John N.; Getman, Daniel P.; Hockerman, Susan; Heintz, Robert; Howard, Susan Carol; Li, Madeleine H.; McDonald, Joseph J.; Carron, Chris P.; Funckes-Shippy, Chris L.; Mehta, Pramod P.; Munie, Grace E.; Swearingen, Craig A. Journal of Medicinal Chemistry, 2005 , vol. 48, # 21 p. 6713 - 6730

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Citation Number: 49

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) ...