HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Arylsulfonamide inhibitors of aggrecanases as potential therapeutic agents for osteoarthritis: synthesis and biological evaluation.

Abstract
Aggrecanases, in particular aggrecanase-2 (ADAMTS-5), are considered the principal proteases responsible for aggrecan degradation in osteoarthritis. For this reason, considerable effort has been put on the discovery and development of aggrecanase inhibitors able to slow down or halt the progression of osteoarthritis. We report herein the synthesis and biological evaluation of a series of arylsulfonamido-based hydroxamates as aggrecanase inhibitors. Compound 18 was found to have a nanomolar activity for ADAMTS-5, ADAMTS-4 and MMP-13 and high selectivity over MMP-1 and MMP-14. Furthermore, this compound proved to be effective in blocking ex vivo cartilage degradation without having effect on cell cytotoxicity.
AuthorsElisa Nuti, Salvatore Santamaria, Francesca Casalini, Kazuhiro Yamamoto, Luciana Marinelli, Valeria La Pietra, Ettore Novellino, Elisabetta Orlandini, Susanna Nencetti, Anna Maria Marini, Silvia Salerno, Sabrina Taliani, Federico Da Settimo, Hideaki Nagase, Armando Rossello
JournalEuropean journal of medicinal chemistry (Eur J Med Chem) Vol. 62 Pg. 379-94 (Apr 2013) ISSN: 1768-3254 [Electronic] France
PMID23376997 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2013 Elsevier Masson SAS. All rights reserved.
Chemical References
  • Matrix Metalloproteinase Inhibitors
  • Protease Inhibitors
  • Sulfonamides
  • ADAM Proteins
  • ADAMTS5 Protein
  • ADAMTS5 protein, human
  • Matrix Metalloproteinases
  • Procollagen N-Endopeptidase
  • ADAMTS4 Protein
  • ADAMTS4 protein, human
Topics
  • ADAM Proteins (antagonists & inhibitors, metabolism)
  • ADAMTS4 Protein
  • ADAMTS5 Protein
  • Dose-Response Relationship, Drug
  • Humans
  • Matrix Metalloproteinase Inhibitors (chemical synthesis, chemistry, pharmacology)
  • Matrix Metalloproteinases (metabolism)
  • Models, Molecular
  • Molecular Structure
  • Osteoarthritis (drug therapy)
  • Procollagen N-Endopeptidase (antagonists & inhibitors, metabolism)
  • Protease Inhibitors (chemical synthesis, chemistry, pharmacology)
  • Structure-Activity Relationship
  • Sulfonamides (chemical synthesis, chemistry, pharmacology)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: