Synthesis of a series of stromelysin-selective thiadiazole urea matrix metalloproteinase inhibitors

…, EL Fritzen, HJ Schostarez, TJ O'Sullivan…

Index: Jacobsen, E. Jon; Mitchell, Mark A.; Hendges, Susan K.; Belonga, Kenneth L.; Skaletzky, Louis L.; Stelzer, Lindsay S.; Lindberg, Thomas J.; Fritzen, Edward L.; Schostarez, Heinrich J.; O'Sullivan, Theresa J.; Maggiora, Linda L.; Stuchly, Christopher W.; Laborde, Alice L.; Kubicek, Marc F.; Poorman, Roger A.; Beck, Joan M.; Miller, Henry R.; Petzold, Gary L.; Scott, Pam S.; Truesdell, Scott E.; Wallace, Tanya L.; Wilks, John W.; Fisher, Christopher; Goodman, Linda V.; Kaytes, Paul S.; Ledbetter, Stephen R.; Powers, Elaine A.; Vogeli, Gabriel; Mott, John E.; Trepod, Catherine M.; Staples, Douglas J.; Baldwin, Eric T.; Finzel, Barry C. Journal of Medicinal Chemistry, 1999 , vol. 42, # 9 p. 1525 - 1536

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Citation Number: 55

Abstract

The synthesis and enzyme inhibition data for a series of thiadiazole urea matrix metalloproteinase (MMP) inhibitors are described. A broad screening effort was utilized to identify several thiadiazoles which were weak inhibitors of stromelysin. Optimization of the thiadiazole leads to include an α-amino acid side chain with variable terminal amide substituents provided a series of ureas which were moderately effective stromelysin ...