Synthesis and Structure−Activity Relationships of β- and α-Piperidine Sulfone Hydroxamic Acid Matrix Metalloproteinase Inhibitors with Oral Antitumor Efficacy

Citations Over TimeTop 16% of 2005 papers

Abstract

alpha-Piperidine-beta-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 beta-sulfones subsequently led to the discovery of hitherto unknown alpha-sulfone hydroxamates that are superior to the corresponding beta-sulfones in potency for target MMPs, selectivity vs MMP-1, and exposure when dosed orally. alpha-Piperidine-alpha-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.

Related Papers

• → Quantitative Structure-Activity Relationship Studies on Matrix Metalloproteinase Inhibitors: Hydroxamic Acid Analogs(2006)13 cited
• → Synthesis and activity of quinolinylmethyl P1′ α-sulfone piperidine hydroxamate inhibitors of TACE(2009)11 cited
• → A quantitative structure-activity relationship study on matrix metalloproteinase inhibitors: Piperidine sulfonamide aryl hydroxamic acid analogs(2007)8 cited
• → A Quantitative Structure-Activity Relationship Study on a Novel Series of Hydroxamic Acid Analogs Acting as Matrix Metalloproteinase Inhibitors(2008)3 cited
• → A Quantitative Structure-Activity Relationship Study on Some Novel Series of Hydroxamic Acid Analogs Acting as Matrix Metalloproteinase Inhibitors(2007)5 cited