Author/Authors :
Jason S. Xiang، نويسنده , , Yonghan Hu، نويسنده , , Thomas S. Rush III، نويسنده , , Jennifer R. Thomason، نويسنده , , Manus Ipek، نويسنده , , Phaik-Eng Sum، نويسنده , , Leila Abrous، نويسنده , , Joshua J. Sabatini، نويسنده , , Katy Georgiadis، نويسنده , , Erica Reifenberg، نويسنده , , Manas Majumdar، نويسنده , , Elisabeth A. Morris، نويسنده , , Steve Tam، نويسنده ,
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 μg/mL and has an oral bioavailability in rat of 35%.
Keywords :
benzofuran , osteoarthritis , Aggrecanase-1 inhibitor , Biphenylsulfonamide carboxylate
