Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Nitrogen containing other than solely as a nitrogen in an...
Patent
1995-06-06
1997-08-05
Weddington, Kevin E.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Nitrogen containing other than solely as a nitrogen in an...
514751, 514754, 514762, 514921, A61K 31135, A61K 3103, A61K 3101
Patent
active
056543433
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
This application is a 371 of PCT/JP94/01695 filed Oct. 11, 1994.
This invention relates to a nitric oxide synthesis inhibitor which is of use as a medicament.
BACKGROUND ART
Resent research has clarified that nitric oxide (NO) is the very vascular endothelium-derived relaxing factor (EDRF) and that it is functioning as a chemical transmitter or modulator not only in vascular endothelial cells but also in such other cells or tissues as the brain, platelet, macrophage, neutrophil, and non-adrenergic, non-cholinergic nervous systems. This nitric oxide is produced by NO synthase using L-arginine (L-Arg) as the substrate. It has been reported that said NO synthase has at least two iso-forms. One is a constitutive-type enzyme which occurs in the vascular endothelium and the brain. The other is an inducible type-enzyme which occurs in the macrophage and vascular smooth muscle. Meanwhile, it is known that the above inducible-type NO synthase is induced by a variety of cytokines such as interleukins (ILs), interferon-.gamma. (IFN-.gamma.), tumor necrosis factor (TNF), etc., or by endotoxins and a broad spectrum of cytokines derived from endotoxins.
It has also been reported that in the event an excess of said nitric oxide is produced and released in the body, various cells and tissues are injured not only by its inherent blood vessel-relaxing effect but also by the chemical reactivity of nitric oxide itself. In particular, it is known that the above-mentioned inducible NO synthase, which is known to be induced by endotoxins and various cytokines, is deeply associated, through the nitric oxide it produces, with the onset and morbidity of endotoxin shock and bleeding tendency. The inducible NO synthase attracts attention in connection with its relation to such morbidity, rather than the physiological roles it plays.
Meanwhile, a variety of inhibitor substances that inhibit synthesis of said nitric oxide are also known and the inhibitors which are most widely used today are various L-arginine derivatives having a methyl or nitro group in the .omega.-position (guanidino group) of L-arginine (L-Arg), which are reversible or irreversible competitive inhibitors of NO synthase for the L-Arg substrate.
Refer to the following reference documents regarding the prior mentioned above for more information. 1992 161-164, 1993, 7, 17
DISCLOSURE OF INVENTION
With the object of providing a nitric oxide synthesis inhibitor substance or composition as a medicine which would take the place of the hitherto-known NO synthase inhibitors mentioned above, the inventors of this invention carried out intensive research, and found that a series of phenanthrene derivatives and salts thereof which they previously developed as substances having interleukin-1 (IL-1) inhibitory activity (JP Kokai H4-211035) possess nitric oxide synthesis inhibitory activity meeting the above object. The invention has been accomplished based on these findings.
This invention, therefore, is directed to a nitric oxide synthesis inhibitor comprising at least one phenanthrene derivative selected from the group consisting of the compounds of the following formulas (1)-(12), or a salt thereof, as an active ingredient. ##STR2## wherein the group --A...B-- represents ##STR3## (R.sup.1 represents hydrogen or lower alkyl), ##STR4## (R.sup.2 represents hydrogen or lower alkanoyl), ##STR5## (R.sup.2 is as defined above), or ##STR6## wherein R.sup.3 represents hydrogen or methyl ##STR7## wherein R.sup.4 represents lower alkanoyloxy; R.sup.2 is as defined above ##STR8## wherein R.sup.5 and R.sup.6 each represent lower alkoxy ##STR9## wherein R.sup.1A represents lower alkyl; R.sup.2A represents formyl; R.sup.3A represents hydroxy; or R.sup.2A and R.sup.3A, taken together, represent oxo; and R.sup.3A may form a double bond in combination with R.sup.5A which is defined below; R.sup.4A represents lower alkyl; R.sup.5A represents hydrogen or hydroxy(lower)alkyl or may form a double bond in combination with R.sup.3A or R.sup.6A which is defined below; R.sup.6A re
REFERENCES:
patent: 5192817 (1993-03-01), Takaishi et al.
patent: 5385947 (1995-01-01), Godel et al.
Adachi Masakazu
Moritoki Hideki
Ono Yukihisa
Takaishi Yoshihisa
Otsuka Pharmaceutical Co. Ltd.
Weddington Kevin E.
LandOfFree
Method of treating a nitric oxide-associated disease with phenan does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Method of treating a nitric oxide-associated disease with phenan, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Method of treating a nitric oxide-associated disease with phenan will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-1075240