Synthesis and evaluation of 2-aryl-4H-3,1-benzoxazin-4-ones as C1r serine protease inhibitors

Bioorganic and Medicinal Chemistry Letters

Volumn 6, Issue 6, 1996, Pages 679-682

  Gilmore, John L ^a   Hays, Sheryl J ^a   Caprathe, Bradley W ^a   Lee, Chitase ^a   Emmerling, Mark R ^a   Michael, Walter ^a   Jaen, Juan C ^a  

^a PFIZER INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4H 3,1 BENZOXAZIN 4 ONE DERIVATIVE; ENZYME INHIBITOR; KALLIKREIN; NAFAMSTAT MESILATE; PLASMIN; SERINE PROTEINASE; THROMBIN; TRYPSIN;

ARTICLE; COMPLEMENT SYSTEM; CONTROLLED STUDY; DRUG SPECIFICITY; DRUG STABILITY; DRUG SYNTHESIS; ENZYME INHIBITION; HUMAN; HUMAN TISSUE; STRUCTURE ACTIVITY RELATION;

EID: 0029873320     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/0960-894X(96)00094-7     Document Type: Article

References (12)

1. (a) Tomlinson, S. Current Opinion in Immunology 1993, 5, 83.
2. (b) Immunology: A Short Course Benjamin, E.; Leskowitz, E., Eds.; Wiley-Liss: New York, 1991; 135.
3. (a) Rogers, J.; Cooper, N. R.; Webtser, S.; Schultz, J.; McGeer, P. L.; Styren, S. D.; Civin, W. H.; Brachova, L.; Bradt, B.; Ward, P.; Lieberburg, I. Proc. Natl. Acad Sci. 1992, 89, 10016.
4. (b)Jiang, H.; Burdick, D.; Glabe, C. G.; Cotman, C. W.; Tenner, A. J. Journal of Immunology 1994, 152, 5050.
5. (a) McGeer, P. L.; Akiyama, H.; Itagaki, S.; McGeer, E. G. Can. J. Neurol. Sci. 1989, 16, 516.
6. (b) McGeer, P. L.; McGeer, E. G.; Kawamata, T.; Yamada, T.; Akiyama, H. Can. J. Neurol. Sci. 1991, 18, 376.
7. Scott, Clay W. and Caputo, Claudia B. Drug News&Perspectives 1994,7(5), 269.
8. Compound 2 was identified as an inhibitor of C1r from a mass screening assay.
9. Aoyama, T.; Ino, Y.; Ozeki, M.; Oda, M.; Sato, T.; Koshiyama, Y.; Suzuki, S.; Fujita, M. Japan Journal of Pharmacology 1984, 35, 203.
10. Bain, D. I.; Smalley, R. K. J Chem. Soc 1968, 13, 1593.
11. McRae, B. J.;Lin, T. Y.; Powers, J. C. J Biol. Chem. 1981, 23, 256.
12. 50 value was determined by plotting % of control activity versus the inhibitor concentration. In all cases, the standard deviation of each calculated mean was less than 10% of the mean of all compounds assayed.