Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Radical -xh acid – or anhydride – acid halide or salt thereof...
Patent
1998-03-11
1999-09-28
Spivack, Phyllis G.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Radical -xh acid, or anhydride, acid halide or salt thereof...
A61K 3119
Patent
active
059589787
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
The present invention relates to a specific cyclooxygenase 2 inhibitor and an anti-inflammatory agent.
BACKGROUND ART
Cyclooxygenase is an enzyme that catalyzes the addition of two oxygen molecules to arachidonic acid isolated from a phospholipid in a cell membrane by phospholipase A.sub.2 to synthesize prostaglandin G.sub.2, and is a rate-determining enzyme in the synthetic system of prostaglandins such as prostaglandin E.sub.2 and thromboxane B.sub.2. Since Vane reported in 1971 that non-steroidal anti-inflammatory drugs such as aspirin and indomethacin inhibit the cyclooxygenase activity to inhibit the production of prostaglandin E.sub.2, thereby manifesting an anti-inflammatory effect, many non-steroidal anti-inflammatory drugs have been developed by pharmaceutical companies. However, most of the non-steroidal anti-inflammatory drugs inhibit the production of not only prostaglandin E.sub.2 in an inflammatory site but also prostaglandin E.sub.2 having a mucosa-protecting effect in digestive tracts, so that they have a stomach and intestine-damaging effect, and this side effect offers a clinical problem.
In recent years, it has been reported that subtype enzymes exist in the cyclooxygenase. Cyclooxygenase 1 conventionally known always manifests itself in cells of the gastric mucosa, seminal vesicle, platelet and the like and is considered to participate in the maintenance of homeostasis in the living body. On the other hand, cyclooxygenase 2 newly discovered is induced by stimulating a cell participating in inflammation such as a macrophage or synovial cell by a cytokine or the like and is hence considered to participate in an inflammatory reaction. The non-steroidal anti-inflammatory drugs clinically used at present are considered to inhibit not only cyclooxygenase 2 but also the cyclooxygenase 1 activity, thereby bringing about an anti-inflammatory effect and at the same time inducing gastrointestinal disorders.
Therefore, it is expected to develop a drug specifically inhibiting the cyclooxygenase 2 activity as a novel anti-inflammatory agent.
Accordingly, it is an object of the present invention to provide a drug which has an effect of specifically inhibiting the cyclooxygenase 2 activity, and an anti-inflammatory agent scarcely having a stomach and intestine-damaging effect.
DISCLOSURE OF THE INVENTION
In view of the foregoing circumstances, the present inventors have carried out an extensive investigation. As a result, it has been found that 2-(2,6-dichloro-4-hydroxyanilino)phenylacetic acid or a salt thereof specifically inhibits cyclooxygenase 2, which catalyzes the synthesis of prostaglandin E.sub.2 produced in an inflammatory site, without inhibiting the activity of cyclooxygenase 1 which catalyzes the synthesis of prostaglandin E.sub.2 produced in the gastric mucosa or the like, and thus the use of this compound provides an excellent anti-inflammatory agent which scarcely causes any gastrointestinal disorders, thus leading to completion of the present invention.
According to the present invention, there is thus provided a specific cyclooxygenase 2 inhibitor which comprises, as an active ingredient, 2-(2,6-dichloro-4-hydroxyanilino)phenylacetic acid represented by the following formula (1): ##STR2## or a salt thereof.
According to the present invention, there is also provided an anti-inflammatory agent which comprises, as an active ingredient, 2-(2,6-dichloro-4-hydroxyanilino)-phenylacetic acid represented by the formula (1) or a salt thereof.
According to the present invention, there is further provided a specific cyclooxygenase 2 inhibitor composition which comprises 2-(2,6-dichloro-4-hydroxyanilino)-phenylacetic acid represented by the formula (1) or a salt thereof and a pharmaceutically acceptable carrier.
According to the present invention, there is still further provided an anti-inflammatory agent composition which comprises 2-(2,6-dichloro-4-hydroxyanilino)-phenylacetic acid represented by the formula (1) or a salt thereof and a pharmaceutically acceptable carrier.
REFERENCES:
Moser et al., J. Med. Chem., 33(9), pp. 2358-2368, 1990.
Hashimoto Shusuke
Matsuzaki Takeshi
Yamazaki Ryuta
Yokokura Teruo
Kabushiki Kaisha Yakul't Honsha
Spivack Phyllis G.
Teikoku Hormone Mfg. Co. Ltd.
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