Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Patent
1993-03-17
1994-06-07
Bernhardt, Emily
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
544295, 544367, 544373, 544374, 544391, 544399, 544402, 548247, A61K 31495, C07D41312, C07D41314, C07D41306
Patent
active
053189701
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
The present invention relates to novel isoxazole compounds having a lipoxygenase inhibiting activity and a cyclooxygenase inhibiting activity, pharmaceutically acceptable salts thereof and medical uses thereof.
BACKGROUND OF THE INVENTION
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 THE INVENTION
The present inventors have conducted a research in considering the foregoing problems in the background, and found that novel isoxazole compounds as indicated in the following formula (1) and pharmaceutically acceptable salts thereof 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 compounds, pharmaceutically acceptable salts thereof, the compounds which are represented by the formula (1): ##STR5## wherein R represents a hydrogen atom or a lower alkoxy group, R.sub.1 is a group represented by the formula (2): ##STR6## (wherein A represents --NH-- or --O--, B represents a methylene group or a carbonyl group, m is 0 or 1, n is an integer of 1 to 12, X represents a hydrogen atom, a hydroxy group or a lower alkoxycarbonyl group, Y represents a phenyl group which can be substituted with one or more halogen atoms, or a hydrogen atom), a group represented by the formula (3): ##STR7## (wherein Z represents a pyrimidinyl group), or a group represented by the formula (4): ##STR8## (wherein R.sub.2 a styryl group which can be substituted with one or more hydroxy groups).
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 a high lipoxygenase inhibitory effect and cyclooxygenase inhibitory effect, and are useful as an anti-asthmatic agent, anti-allergic agent, agent for treating encephalopathy, cardiovascular agent, agent for treating nephritis, anti-inflammatory analgesic agent, anti-rheumatic agent, agent for treating dermatosis such as psoriasis and liver disease agent.
Accordingly, the present invention provides an anti-asthmatic agent, anti-allergic agent, agent for treating encephalopathy, cardiovascular agent, agent for treating nephritis, anti-inflammatory analgesic agent, anti-rheumatic agent, agent for treating dermatosis such as psoriasis and liver disease agent, the agents each comprising an effective amount of the compound of the formula (1) or a pharmaceutically acceptable salt thereof, and a pharmaceutical carrier.
The present invention provides a method for treating asthma, allergy, encephalopathy, circulatory diseases, nephritis, inflammation, rheumatism, dermatosis such as psoriasis and liver disease, characterised in that an effective amount of the compound of the formula (1) or a pharmaceutically acceptable salts thereof are administered to a patient.
When the compounds represented by the formula (1) have an asymmetric carbon atom, the isoxazole compounds of the invention include R form, S form and a mixture of R form and S form in any rate.
Examples of a lower alkoxy group represented by R and of a lower alkoxy groups of a lower alkoxycarbonyl group represented by X in the present invention are straight- or branched-chain alkoxy groups having 1 to 4 carbon atoms, such as methoxy group, ethoxy group, n-propoxy group, isopr
REFERENCES:
patent: 3642812 (1972-02-01), Southern
patent: 4327222 (1982-04-01), Micetich et al.
patent: 5182284 (1993-01-01), Suzuki et al.
patent: 5229386 (1993-07-01), Takasugi et al.
Kajitani Makoto
Nozaki Kenji
Ono Naohiko
Shindo Takashi
Suzuki Masahiro
Bernhardt Emily
Taiho Pharmaceutical Co. Ltd.
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