Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1993-11-01
1995-03-21
Lee, Mary C.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
514340, 548247, 548248, 546275, A61K 3142, A61K 3144, C07D26108, C07D21316
Patent
active
053995775
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 of PCT/JP92/00571 filed May 1, 1992.
TECHNICAL FIELD
The present invention relates to novel isoxazole derivatives having lipoxygenase inhibiting activity and cyclooxygenase inhibiting activity, salts thereof, and medical use thereof.
BACKGROUND ART
It is considered that leukotrienes produced by 5-lipoxygenase from arachidonic acid and prostaglandins produced by cyclooxygenase from arachidonic acid are deeply concerned in a crisis of allergic asthma, allergic rhinitis, inflammation, etc. Consequently it is desired to inhibit both 5-lipoxygenase and cyclooxygenase in order to strongly and properly inhibit various allergic diseases, inflammations and other diseases. The development of a drug inhibiting both enzymes is earnestly desired.
DISCLOSURE OF INVENTION
The present inventors have conducted a research in considering the foregoing problems in the background art, and found that novel isoxazole derivatives as indicated in the following formula (1) have an excellent lipoxygenase inhibiting activity and an excellent cyclooxygenase inhibiting activity, and are useful as a drug. Thus, the present invention has been accomplished.
The present invention provides isoxazole derivatives represented by the general formula (1) or a salt thereof: ##STR2## [wherein R and R' are the same or different and each is a hydrogen atom, a lower alkyl group, a lower alkoxy group or a halogen atom: m is 0 to 5; A is --NH--, --O-- or a direct bond; B is --C(.dbd.Z)--NH--, --C(.dbd.Z)--(CH.dbd.CH).sub.l -- or --CH.dbd.CH-- (wherein Z is an oxygen or sulfur atom and l is 0 to 2); X is a nitrogen or carbon atom; n is 0 to 3; and Y is a hydroxy group, a lower alkoxy group, a lower alkyl group, a lower alkoxycarbonyloxy group, a lower alkoxycarbonylmethyloxy group, a carboxylmethyloxy group, an amino acid residue which may have a protective group, a lower alkylcarbonyloxy group, a pyridylcarbonyloxy group, a dimethylaminophenylcarbonyloxy group or a diloweralkyl phosphate residue; provided that when n is 2 or 3, the two or three Ys are the same or different and each is one of the groups mentioned above, that when n is 2 or more, two Ys may form a methylenedioxy group, that when X is a nitrogen atom, n is 0 and that when A is --NH--, m is 1 to 5].
The compounds of the present invention represented by the formula (1) has an excellent lipoxygenase inhibiting activity and cyclooxygenase inhibiting activity. Examples of lipoxygenases are 5-lipoxygenase, 12-lipoxygenase and 15-lipoxygenase, etc. The compounds of the invention exhibit, in particular, a potent activity of 5-lipoxygenase inhibition.
The compounds of the invention have excellent lipoxygenase inhibiting and cyclooxygenase inhibiting activities and are useful as antiasthmatic agents, antiallergic agents, agents for treating encephalopathy, cardiovascular agents, agents for treating nephritis, antiinflammatory analgesic agents, antirheumatic agents, agents for treating dermatosis such as psoriasis, and liver disease agents.
Accordingly, the present invention provides antiasthmatic agents, antiallergic agents, agents for treating encephalopathy, cardiovascular agents, agents for treating nephritis, antiinflammatory analgesic agents, anti-rheumatic agents, agents for treating dermatosis such as psoriasis, and liver disease agents, the agents each comprising an effective amount of a compound of the general formula (1) given above and a pharmaceutically acceptable carrier therefor.
The present invention also provides a method for treating asthma, allergy, encephalopathy, circulatory diseases, nephritis, inflammation, rheumatism, dermatosis such as psoriasis, and liver diseases which comprises administering an effective amount of a compound of the general formula (1) given above to patients.
The present invention is further concerned with the use of compounds of the general formula (1) given above in the treatment of asthma, allergy, encephalopathy, circulatory diseases, nephritis, inflammation, rheumatism, dermatosis such as psoriasis, and liver diseas
REFERENCES:
Patent Abstracts of Japan, vol. 009, No. 211, 1990.
Patent Abstracts of Japan, vol. 014, No. 535, 1985.
Tetrahedron Letters No. 47, pp. 3495-3497 (1964).
CA 3842j 1,3-Dipolar . . . Ketones. L'Abbe et al., p. 313, 1974.
CA 118:254919s Preparation of . . . inhibitors. Shindo et al., p. 886, 1993.
Akizawa Yushiro
Matsuura Naosuke
Nozaki Kenji
Ono Naohiko
Shindo Takashi
Lee Mary C.
McKane Joseph K.
Taiho Pharmaceutical Co. Ltd.
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