2-Amino-4H-3,1-benzoxazin-4-ones as Inhibitors of C1r Serine Protease
Journal of Medicinal Chemistry1998Vol. 41(7), pp. 1060–1067
Citations Over TimeTop 13% of 1998 papers
Sheryl J. Hays, Bradley W. Caprathe, John L. Gilmore, Nilam Amin, Mark R. Emmerling, Walter Michael, Ravi Nadimpalli, Rathna Nath, Kadee J. Raser, Daniel Stafford, Desiree Watson, Kevin Wang, Juan C. Jaén
Abstract
A series of 2-amino-4H-3,1-benzoxazin-4-ones have been synthesized and evaluated as inhibitors of the complement enzyme C1r. C1r is a serine protease at the beginning of the complement cascade, and complement activation by beta-amyloid may represent a major contributing pathway to the neuropathology of Alzheimer's disease. Compounds such as 7-chloro-2-[(2-iodophenyl)-amino]benz[d][1,3]oxazin-4-one (32) and 7-methyl-2-[(2-iodophenyl)amino]benz[d][1,3]oxazin-4-one (37) show improved potency compared to the reference compound FUT-175. Many of these active compounds also possess increased selectivity for C1r compared to trypsin and enhanced hydrolytic stability relative to 2-(2-iodophenyl)-4H-3,1-benzoxazin-4-one (1).
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