2. Academic Validation
  3. Orally active MMP-1 sparing α-tetrahydropyranyl and α-piperidinyl sulfone matrix metalloproteinase (MMP) inhibitors with efficacy in cancer, arthritis, and cardiovascular disease

Orally active MMP-1 sparing α-tetrahydropyranyl and α-piperidinyl sulfone matrix metalloproteinase (MMP) inhibitors with efficacy in cancer, arthritis, and cardiovascular disease

  • J Med Chem. 2010 Sep 23;53(18):6653-80. doi: 10.1021/jm100669j.
Daniel P Becker 1,  Thomas E Barta,  Louis J Bedell,  Terri L Boehm,  Brian R Bond,  Jeffery Carroll,  Chris P Carron,  Gary A Decrescenzo,  Alan M Easton,  John N Freskos,  Chris L Funckes-Shippy,  Marcia Heron,  Susan Hockerman,  Carol Pearcy Howard,  James R Kiefer,  Madeleine H Li,  Karl J Mathis,  Joseph J McDonald,  Pramod P Mehta,  Grace E Munie,  Teresa Sunyer,  Craig A Swearingen,  Clara I Villamil,  Dean Welsch,  Jennifer M Williams,  Ying Yu,  Jun Yao
Affiliations

Affiliation

  • 1 Pfizer Research, 700 Chesterfield Village Parkway, St. Louis, Missouri 63198, USA. dbecke3@luc.edu
PMID: 20726512 DOI: 10.1021/jm100669j
Abstract

α-Sulfone-α-piperidine and α-tetrahydropyranyl hydroxamates were explored that are potent inhibitors of MMP's-2, -9, and -13 that spare MMP-1, with oral efficacy in inhibiting tumor growth in mice and left-ventricular hypertrophy in rats and in the bovine cartilage degradation ex vivo explant system. α-Piperidine 19v (SC-78080/SD-2590) was selected for development toward the initial indication of Cancer, while α-piperidine and α-tetrahydropyranyl hydroxamates 19w (SC-77964) and 9i (SC-77774), respectively, were identified as backup compounds.

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