Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1994-12-13
1996-11-12
Dees, Jos e G.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
549289, A61K 3137, C07D31120
Patent
active
055740626
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 of PCT/JP94/00615 filed 12 Apr. 1994 and published as WO94/24119 Oct. 27, 1994.
TECHNICAL FIELD
The present invention relates to novel coumarin derivatives inhibiting 12-lipoxygenase selectively, and medicines containing these compounds as effective ingredients; and furthermore, the present invention relates to coumarin derivatives having a effect of inhibiting 12-lipoxygenase activities in the 12-lipoxygenase pathway selectively, and medicines containing the compounds as effective ingredients and having the effect of inhibiting 12-lipoxygenase selectively being useful as medicines for preventing and treating various circulatory diseases such as arteriosclerosis and vasospasm and for preventing the metastasis of some kinds of cancers (e.g., Lewis lung cancer).
In addition, the present invention relates to novel coumarin derivatives capable of forming substances inhibiting 12-lipoxygenase selectively through the cleavage of their modified moieties in vivo, and medicines containing these compounds as effective ingredients; and furthermore, the present invention relates to coumarin derivatives (hereinafter may be referred to as precursors) capable of converting to compounds inhibiting 12-lipoxygenase activities in the 12-lipoxygenase pathway, and medicines containing the precursors as effective ingredients and having a effect of inhibiting 12-lipoxygenase selectively being useful as medicines for preventing and treating various circulatory diseases such as arteriosclerosis and vasospasm and for preventing the metastasis of some kinds of cancers (e.g., Lewis lung cancer).
In the present specification, the indication of percentage means values by weight unless otherwise specified, and an IC.sub.50 value means a mol concentration to produce 50% inhibition of 5-lipoxygenase or 12-lipoxygenase activities.
BACKGROUND ART
It is known that there exists a metabolic pathway called a 5-lipoxygenase pathway in the cascade of arachidonic acid and that arachidonic acid is converted to 5-hydroperoxyeicosatetraenoic acid (hereinafter may be referred to as 5-HPETE) by the function of 5-lipoxygenase ("Prostaglandin and Morbid States", edited by Seiitsu Murota, Tokyo Kagaku Dojin, 1984).
It is known that various leukotrienes can be synthesized by using this compound as an intermediate ("prostaglandin and Mobid States", edited by Seiitsu Murota, Tokyo Kagaku Dojin, 1984), and it is also known that, for example, leukotriene B4 of these leukotrienes has a strong activity of leukocyte migration and is a mediator for inflammation, and that leukotriene C4 and D4 are mediators for asthma ("Prostaglandin and Morbid States", edited by Seiitsu Murota, Tokyo Kagaku Dojin, 1984).
Hence, searches for medicines having an inhibitory effect on 5-lipoxygenase have been performed extensively from the view point that it may be anticipated to prevent and treat various diseases caused by the excess production of leukotrienes (e.g., allergic diseases, bronchial asthma, edema, various inflammatory diseases) by using medicines capable of inhibiting 5-lipoxygenase effectively, which is an incipient enzyme of a biosynthesis system of these leukotrienes.
On the other hand, there exists a metabolic pathway called a 12-lipoxygenase pathway in the cascade of arachidonic acid. 12-lipoxygenase is an enzyme present in platelets in a large amount and reacts with arachidonic acid to form 12-hydroperoxyeicosatetraenoic acid (hereinafter may be referred to as 12-HPETE), which is reduced to 12-hydroxyeicosatetraenoic acid (hereinafter may be referred to as 12-HETE).
The physiological meaning of metabolic products in the 12-lipoxygenase pathway has not been clear compared with that of the 5-lipoxygenase pathway, but recently various physiological activities of the metabolic products have become clear mainly on 12-HPETE and 12-HETE of its main metabolic products.
Physiological activities thereof may be exemplified as below. Namely, a possibility is pointed out that 12-lipoxygenase metabolic products may be concerned with arterioscleros
REFERENCES:
patent: 2857401 (1958-10-01), Rorig
patent: 3351482 (1967-11-01), Raue
patent: 3515721 (1970-06-01), Ritter et al.
patent: 3585214 (1971-06-01), Boschetti et al.
patent: 3644413 (1972-02-01), Rao et al.
patent: 3733338 (1973-05-01), Kimura et al.
patent: 4737517 (1988-04-01), della Valle et al.
patent: 4918092 (1990-04-01), Frenette et al.
patent: 5281721 (1994-01-01), Powers et al.
patent: 5424320 (1995-06-01), Fortin et al.
Hamano Hirokazu
Hashimoto Koichi
Mori Shigehiro
Moriuchi Hisako
Yamada Akio
Dees Jos e G.
Lambkin Deborah
Morinaga Milk Industry Co. Ltd.
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