Synthesis and biological evaluation of biphenylsulfonamide carboxylate aggrecanase-1 inhibitors

Autor:	Jennifer R. Thomason, Phaik-Eng Sum, Elisabeth A. Morris, Erica Reifenberg, Tam Steve Yik-Kai, Yonghan Hu, Manas K. Majumdar, Thomas S. Rush, Katy E. Georgiadis, Leila Abrous, Jason Shaoyun Xiang, Manus Ipek, Joshua James Sabatini
Rok vydání:	2006
Předmět:	Models Molecular Clinical Biochemistry Carboxylic Acids Drug Evaluation Preclinical Administration Oral Pharmaceutical Science Osteoarthritis Matrix Metalloproteinase Inhibitors Crystallography X-Ray Biochemistry Structure-Activity Relationship Matrix Metalloproteinase 13 Drug Discovery medicine Animals Collagenases Enzyme Inhibitors Molecular Biology Aggrecan Aggrecanase chemistry.chemical_classification Sulfonamides Molecular Structure biology Cartilage Biphenyl Compounds Organic Chemistry medicine.disease In vitro Rats ADAM Proteins Enzyme medicine.anatomical_structure chemistry Proteoglycan Enzyme inhibitor ADAMTS4 Protein biology.protein Molecular Medicine Proteoglycans Procollagen N-Endopeptidase
Zdroj:	Bioorganic & Medicinal Chemistry Letters. 16:311-316
ISSN:	0960-894X
DOI:	10.1016/j.bmcl.2005.10.001
Popis:	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%.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::09e990d97f59210a9bc14ea6a6dd2edb https://doi.org/10.1016/j.bmcl.2005.10.001 Zobrazit plný text záznamu Full Text from ScienceDirect