联苯磺酰胺羧酸酯聚集蛋白聚糖酶-1抑制剂的合成与生物学评价
Synthesis and biological evaluation of biphenylsulfonamide carboxylate aggrecanase-1 inhibitors.
作者信息
Xiang Jason S, Hu Yonghan, Rush Thomas S, Thomason Jennifer R, Ipek Manus, Sum Phaik-Eng, Abrous Leila, Sabatini Joshua J, Georgiadis Katy, Reifenberg Erica, Majumdar Manas, Morris Elisabeth A, Tam Steve
机构信息
Department of Chemical and Screening Sciences, Wyeth Research, 200 Cambridge Park Drive, Cambridge, MA 02140, USA.
出版信息
Bioorg Med Chem Lett. 2006 Jan 15;16(2):311-6. doi: 10.1016/j.bmcl.2005.10.001. Epub 2005 Nov 3.
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%.
聚集蛋白聚糖酶是最近发现的能够切割聚集蛋白聚糖（软骨的一种关键成分）的酶。聚集蛋白聚糖酶抑制剂可能提供一种独特的方法来阻止骨关节炎中软骨破坏的进展。本文报道了1型聚集蛋白聚糖酶的联苯磺酰胺羧酸抑制剂的合成与评估。化合物24在浓度为10微克/毫升时对蛋白聚糖降解的抑制率达89%，在大鼠体内的口服生物利用度为35%。
Zotero 插件