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Studies on 2-benzyloxy-4H-3,1-benzoxazin-4-ones as serine protease inhibitors. 1998

M Gütschow, and U Neumann, and J Sieler, and K Eger
Institut für Pharmazie, Universität Leipzig, Germany. guetscho@uni-leipzig.de

The class of 3,1-benzoxazin-4-ones includes potent inhibitors of various serine proteases. Structural investigation on three 2-benzyloxy-4H-3,1-benzoxazin-4-ones (1-3) are described with respect to their reactivity to alkaline hydrolysis. The 13C NMR data of 2-benzyloxy-5-methyl-4H-3,1-benzoxazin-4-one 3 are discussed. This peri substituted compound was subjected to a crystal structure analysis. The heterocyclic skeleton together with the carbonyl oxygen and the methyl carbon is planar, and only small angle distortions occurred. The inhibition of neutrophil serine proteases by 1-3 is reported. The different reactivity of the 5-methyl derivative 3 towards serine proteases is mainly influenced by specific interactions within the active sites. Thus, 3 was found to rapidly acylate human leukocyte proteinase 3 and exhibited a Ki value of 1.8 nM.

UI MeSH Term Description Entries
D007700 Kinetics The rate dynamics in chemical or physical systems.
D007962 Leukocytes White blood cells. These include granular leukocytes (BASOPHILS; EOSINOPHILS; and NEUTROPHILS) as well as non-granular leukocytes (LYMPHOCYTES and MONOCYTES). Blood Cells, White,Blood Corpuscles, White,White Blood Cells,White Blood Corpuscles,Blood Cell, White,Blood Corpuscle, White,Corpuscle, White Blood,Corpuscles, White Blood,Leukocyte,White Blood Cell,White Blood Corpuscle
D010078 Oxazines Six-membered heterocycles containing an oxygen and a nitrogen.
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D006868 Hydrolysis The process of cleaving a chemical compound by the addition of a molecule of water.
D015842 Serine Proteinase Inhibitors Exogenous or endogenous compounds which inhibit SERINE ENDOPEPTIDASES. Serine Endopeptidase Inhibitor,Serine Endopeptidase Inhibitors,Serine Protease Inhibitor,Serine Protease Inhibitors,Serine Proteinase Antagonist,Serine Proteinase Antagonists,Serine Proteinase Inhibitor,Serine Proteinase Inhibitors, Endogenous,Serine Proteinase Inhibitors, Exogenous,Serine Protease Inhibitors, Endogenous,Serine Protease Inhibitors, Exogenous,Antagonist, Serine Proteinase,Endopeptidase Inhibitor, Serine,Inhibitor, Serine Endopeptidase,Inhibitor, Serine Protease,Inhibitor, Serine Proteinase,Protease Inhibitor, Serine,Proteinase Antagonist, Serine,Proteinase Inhibitor, Serine
D048588 Benzoxazines OXAZINES with a fused BENZENE ring. Benzoxazine,Benzoxazinoid,Benzoxazinone,Benzoxazinones,Benzoxazinoids
D018360 Crystallography, X-Ray The study of crystal structure using X-RAY DIFFRACTION techniques. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed) X-Ray Crystallography,Crystallography, X Ray,Crystallography, Xray,X Ray Crystallography,Xray Crystallography,Crystallographies, X Ray,X Ray Crystallographies
D019272 Leukocyte Elastase An enzyme that catalyzes the hydrolysis of proteins, including elastin. It cleaves preferentially bonds at the carboxyl side of Ala and Val, with greater specificity for Ala. EC 3.4.21.37. Lysosomal Elastase,Neutrophil Elastase,PMN Elastase,Polymorphonuclear Leukocyte Elastase,Granulocyte Elastase,Elastase, Granulocyte,Elastase, Leukocyte,Elastase, Lysosomal,Elastase, Neutrophil,Elastase, PMN,Elastase, Polymorphonuclear Leukocyte,Leukocyte Elastase, Polymorphonuclear
D066298 In Vitro Techniques Methods to study reactions or processes taking place in an artificial environment outside the living organism. In Vitro Test,In Vitro Testing,In Vitro Tests,In Vitro as Topic,In Vitro,In Vitro Technique,In Vitro Testings,Technique, In Vitro,Techniques, In Vitro,Test, In Vitro,Testing, In Vitro,Testings, In Vitro,Tests, In Vitro,Vitro Testing, In

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