Chemistry: molecular biology and microbiology – Enzyme – proenzyme; compositions thereof; process for... – Enzyme inactivation by chemical treatment
Patent
1989-02-03
1990-12-25
Shah, Mukund J.
Chemistry: molecular biology and microbiology
Enzyme , proenzyme; compositions thereof; process for...
Enzyme inactivation by chemical treatment
514 2, 514 18, 514 19, 5142302, 530331, 544 92, 544 93, C07D26510, C12N 999, A61H 3700, A61H 31535
Patent
active
049802879
DESCRIPTION:
BRIEF SUMMARY
DESCRIPTION
1. Technical Field
The present invention relates to 4H-3,1-benzoxazin-4-one compounds and pharmaceutical compositions containing same as an effective component for inhibiting serine proteases.
More particularly, the present invention relates to 4H-3,1-benzoxazin-4-one compounds useful for blocking degeneration, destruction or inflammation of tissues caused by the action of proteases, especially, elastase, on mammalian proteins such as elastin, and pharmaceutical compositions containing same as an effective component for inhibiting serine proteases, especially elastase.
2. Background Art
Elastin is a fibrous protein which forms a principal component of elastic fibers in connective tissues and has a rubber-like elasticity, and is contained in a large amount in lungs, bronchi, and aortas.
Elastase is a group of proteases capable of hydrolyzing elastin, and is produced in pancreata and polymorphonuclear leukocytes of mammals or by certain types of microorganisms. The elastase produced in the leukocytes plays an important role in the digestion of phagocytosed bacteria, but when leaked from the cell to the outside, the elastase attacks tissue elastin and causes degeneration, destruction or inflammation of tissues.
This excessive digestion of elastin by the elastase is considered to be a cause of pulmonary emphysema, adult respiratory distress syndrome, pulmonary fibrosis, bronchitis, pneumonia, rheumatoid arthritis, arteriosclerosis, sepsis, shock, pancreatitis, nephritis, and certain dermatosis.
Accordingly, an elastase inhibitor is considered to be useful as a remedy or preventive for the abovementioned diseases.
A group of 4H-3,1-benzoxazin-4-one compounds having, as a basic structure, the chemical formula: ##STR2## are known substances capable of inhibiting serine proteases.
For example, Teshima et al. (J. BIOL. CHEM., vol. 257, pages 5085 to 5091 (1982)) reported various types of 2-alkyl-4H-3,1-benzoxazin-4-one compounds and Hedstrom et al. (BIOCHEMISTRY, vol 23, pages 1753 to 1759 (1984)) reported 2-ethoxy-4H-3,1-benzoxazin-4-one. Also, Spenser et al. (BIOCHEM. BIOPHYS. RES. COMMUN., vol. 140, pages 923 to 933 (1986)) reported that 5-methyl substituted 2-alkyl-4H-3,1-benzoxazin-4-one exhibits a strong elastase inhibitory activity.
Furthermore, Japanese Unexamined Patent Publication (Kokai) No. 60-169467 for Syntax Inc., published on Sept. 2, 1985 discloses 2-amino derivatives of 4H-3,1-benzoxazin-4-one, and Japanese Unexamined Patent Publication No. 62-30770 for Syntex Inc., published on Feb. 9, 1987 discloses 2-oxy derivatives of 4H-3,1-benzoxazin-4-one.
It is known that most of the above-mentioned compounds exhibit a higher inhibiting activity for chymotrypsin than for elastase.
DISCLOSURE OF THE INVENTION
An object of the present invention is to provide 4H-3,1-benzoxazin-4-one compounds having a strong inhibitory activity against serine proteases and pharmaceutical compositions containing the same as an effective component for inhibiting serine proteases.
Another object of the present invention is to provide 4H-3,1-benzoxazin-4-one compounds having a high inhibitory activity selective for the elastase among serine proteases, and pharmaceutical compositions containing the same as an effective component for inhibiting the elastase.
The above-mentioned objects are attained by the compound of the present invention.
The 4H-3,1-benzoxazin-4-one compound of the present invention is of the formula (I): ##STR3## wherein R represents a member selected from hydrogen atom and alkyl radicals, A represents a member selected from amino acid residues and peptides having 2 to 3 amino acid residues, which amino acid residues may have side chains protected by protective radicals, X represents a member selected from alkyl radicals, fluoroalkyl radicals, and radicals of the formulae OR.sup.1 and NHR.sup.1 in which R.sup.1 represents an alkyl radical, and Y represents a protective radical for an amino radical, and salts thereof.
The pharmaceutical composition of the present invention for inhibiting serine pro
REFERENCES:
patent: 4657893 (1987-04-01), Krantz et al.
Teshima et al., Journal of Biological Chemistry, 257(9), 1982, pp. 5085-5891.
Spencer et al., Biochem. Biophys. Research Commun., 140(3), 1986, pp. 928 to 933.
Hedstrom et al., Biochemistry 23, 1984, 1753-1759.
Krantz et al., J. Mec. Chem., 1990, 33, 464-479.
Fujii Katsuhiko
Kokubo Masayuki
Oshida Jun-ichi
Tomimori Koji
Uejima Yasuhide
Shah Mukund J.
Teijin Limited
Ward E. C.
LandOfFree
4H-3,1-benzoxazin-4-one compounds and pharmaceutical composition does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with 4H-3,1-benzoxazin-4-one compounds and pharmaceutical composition, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and 4H-3,1-benzoxazin-4-one compounds and pharmaceutical composition will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-1162324