Synthesis and biological evaluation of biphenylsulfonamide carboxylate aggrecanase-1 inhibitors.

Basic Information

ID: ALA1147767

Journal: Bioorg Med Chem Lett

Title: Synthesis and biological evaluation of biphenylsulfonamide carboxylate aggrecanase-1 inhibitors.

Authors: Xiang JS, Hu Y, Rush TS, Thomason JR, Ipek M, Sum PE, Abrous L, Sabatini JJ, Georgiadis K, Reifenberg E, Majumdar M, Morris EA, Tam S.

Abstract: Aggrecanases are recently discovered enzymes that cleave aggrecan, a key component of cartilage. Aggrecanase inhibitors may provide a unique means to halt the progression of cartilage destruction in osteoarthritis. The synthesis and evaluation of biphenylsulfonamidocarboxylic acid inhibitors of aggrecanase-1 are reported. Compound 24 demonstrated 89% inhibition of proteoglycan degradation at 10 microg/mL and has an oral bioavailability in rat of 35%.

CiteXplore: 16275085

DOI: 10.1016/j.bmcl.2005.10.001

Patent ID: