Benzofuran derivative and pharmaceutical comprising the same as

Details Benzofuran derivative and pharmaceutical comprising the same as Benzofuran derivative and pharmaceutical comprising the same as

1991-07-16

1993-09-14

Dentz, Bernard

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Having -c-, wherein x is chalcogen, bonded directly to...

549462, A61K 3134, C07D30786

Patent

active

052449181

DESCRIPTION:

BRIEF SUMMARY
FIELD OF THE INVENTION

The present invention relates to benzofuran derivatives possessing inhibitory activity against 5-lipoxygenase which is one of the lipoxygenase metabolic enzymes involving the arachidonate cascade, and, because of this activity, useful for the treatment and prevention of allergic diseases such as bronchial asthma and various inflammatory diseases. The present invention also relates to a process for the preparation of the benzofuran derivatives and a pharmaceutical composition comprising the same.


BACKGROUND ART

A number of factors such as histamine, serotonin, prostaglandin (PG), leukotriene (LT), thromboxane (TX), platelet activation factors, lysolecithin, various types of lymphokine, and the like are involved in the allergic diseases such as bronchial asthma and various inflammatory diseases. Among these factors, PG and LT play particularly important functions in the allergic diseases such as bronchial asthma and various inflammatory diseases because of a number of their analogs and the varieties in their physiological activities. Disorders in the arachidonate metabolic system induces insufficiency or excess in the arachidonate metabolic products such as PG, LT, and TX in the cells, which, in turn, causes many types of pathological conditions, such as vascular permeability progress, bronchial contraction, platelet agglomeration, and the like, leading to various inflammatory diseases and allergic diseases. A number of chemicals which specifically inhibit various enzymes involving the arachidonate metabolic system have been developed as anti-inflammatory drugs; for example, non-steroidal anti-inflammatory drugs, e.g. aspirin and indomethacin, which exhibit anti-inflammatory activity by inhibiting cyclooxygenase activity thereby controlling the production of PG. These drugs are effective for inflammation related to the PG system, but cannot inhibit inflammation induced by LTs. Slow reacting substance of anaphylaxis (SRS-A) is known as a strong chemical mediator of bronchial asthma. SRS-A is a mixture of CTC.sub.4, LTD.sub.4, and LTE.sub.4. LTB.sub.4 has strong leukocyte inducing and activating activities, and thus a great attention is given to its involvement in inflammation. Therefore, compounds inhibiting 5-lipoxygenase activity which is the first enzyme catalyzing the production of LTs from arachidonic acid are anticipated to be effective for the treatment or prevention of allergic diseases such as bronchial asthma and various inflammatory diseases.
There are a number of publications reporting compounds having 5-lipoxygenase inhibitory activity from this aspect. Japanese Patent Laid-open (kokai) No. 213276/1989, for example, describes a benzofuran derivative possessing 5-lipoxygenase inhibitory activity and TXA.sub.2 biosynthesis inhibitory activity.
Compounds heretofore reported as having 5-lipoxygenase inhibitory activity are not sufficient in their anti-allergic activity, anti-inflammatory activity, and safety. No such compounds are commercially sold as a drug.
The present inventors have screened a number of metabolic products produced by microorganisms using the 5-lipoxygenase inhibitory activity as an index of screening anti-allergic and anti-inflammatory activities. As a result, the present inventors have found a novel benzofuran derivative produced by a microorganism belonging to genus Codinaea possessed remarkable 5-lipoxygenase inhibitory activity as well as anti-allergic and anti-inflammatory activities, and was useful as a medicine. The finding has led to the completion of the present invention.


DISCLOSURE OF THE INVENTION

The present invention provides a benzofuran derivative having the following general formula (I), ##STR2## wherein R.sub.1 and R.sub.2 may be the same or different and represent a hydrogen atom or a lower alkyl group and R.sup.3 represents a group --CH.dbd.CH--CH.dbd.CH--CH.sub.3 or a group --(CH.sub.2).sub.4 CH.sub.3, a process for the preparation of the benzofuran derivative, a pharmaceutical composition comprising the same, and a microorganism

REFERENCES:
patent: 4978761 (1991-12-01), Goto et al.
Ayer et al., Can. J. Microbiol., vol. 36(2), pp. 83-85 (1990).
Pfefferle et al., Journal of Antibiotics, vol. XLIII (6), pp. 648-654 (Jun. 1990).

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