Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Radical -xh acid – or anhydride – acid halide or salt thereof...
Patent
1995-01-25
1997-06-24
Seidleck, James J.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Radical -xh acid, or anhydride, acid halide or salt thereof...
514574, A61K 3120
Patent
active
056418108
DESCRIPTION:
BRIEF SUMMARY
The present invention concerns the use of .alpha., .omega.-dicarboxylic acids for the preparation of medicaments for the prevention and treatment of fibrinogen-mediated obstructive occurrences in blood vessels.
Fibrinogen is a glycoprotein in the blood which plays an essential part in haemostasis and maintenance of the blood viscosity. It participates in the formation of platelet aggregates and in the coagulation cascade. By means of thrombin, fibrinogen is converted into fibrin monomers which, after polymerisation, form the basis for haemostatic occlusions.
Besides other things, fibrinogen is an independent risk factor (J. Inter. Med., 227, 365-373, 1990) for cardiovascular diseases, as has been shown in various large prospective clinical studies (summarised in TiPS, 11, 444-451, 1990). Increased plasma fibrinogen levels are frequently associated with a dyslipidaemia but also with peripheral vascular occlusive disease, hypertension and diabetes (J. Am. Med. Assoc., 258, 1193-1186, 1987; J. Am. Med., 85, 584-585, 1988). The occulsion rate after by-pass operations is also correlated with the level of the plasma fibrinogen (Brit. Med. J., 199, 643-646, 1989). It is generally accepted that increased fibrinogen levels lead to morphological changes in the blood vessels and are not a result of these (J. Intern. Med., 227, 365-373, 1990).
Active materials which lead to a lowering of the plasma fibrinogen are, therefore, of therapeutic value in a number of pathological states.
The task forming the basis of the present invention is to make available suitable medicaments which can be used for the treatment of hyperfibrinogenaemia.
In the scope of the present invention, it has now, surprisingly, been found that .alpha., .omega.dicarboxylic acids of the following formula I lead to a lowering of the fibrinogen in the plasma of various animal species or mitigate the increase of fibrinogen in blood plasma after stimulation. Therefore, the substances are suitable for the treatment or prevention of hyperfibrinogenaemias as a result of which obstructive blood vessel diseases arise, such as e.g. in the case of arteriosclerotic changes, diseases of the venous system resulting in thrombotic and embolic complications or hyperfibrinogenaemias after angioplastic procedures and inflammatory or neoplastic processes.
The subject of the present invention are .alpha.,.omega.-dicarboxylic acids of the general formula I ##STR2## in which X and X, which can be the same or different, signify hydrogen, halogen, C.sub.1 -C.sub.6 -alkyl, C.sub.1 -C.sub.6 -alkoxy, hydroxyl, cyano, carboxyl, C.sub.1 -C.sub.6 -alkoxycarbonyl or carbamoyl, R.sub.1 and R.sub.2, which can be the same or different, hydrogen or C.sub.1 -C.sub.6 -alkyl and Q a linear saturated or unsaturated alkylene chain with 2-14 C-atoms in which one or more C-atoms can be replaced by cycloalkyl rings, phenyl or heterocycles, as well as their in vivo-hydrolysable carboxylic acid derivatives.
Preferred are compounds of the formula I in which X and Y, which can be the same or different, signify hydrogen or halogen, R.sub.1 and R.sub.2, which can be same or different, hydrogen or methyl and Q a linear chain with 2-14 C-atoms, a --(CH.sub.2).sub.n -cyclohexylidene-(CH.sub.2).sub.n --, a --(CH.sub.2).sub.m -phenylene-(CH.sub.2).sub.m --, a --CH.sub.2 --CH.dbd.CH-phenylene--CH.dbd.CH--CH.sub.2 -- or a --CH.sub.2 --CH.dbd.CH--CH.sub.2 -phenylene-CH.sub.2 CH.dbd.CH--CH.sub.2 -- group, whereby n represents the numbers 2, 3 or 4 and m the numbers 3 or 4, as well as their in vivo-hydrolysable carboxylic acid derivatives.
Especially preferred are the two compounds of the formula I in which X and Y each signify hydrogen, R.sub.1 and R.sub.2 each a methyl group and Q a --(CH.sub.2).sub.10 -- group (compound A) and X and Y each chlorine, R.sub.1 and R.sub.2 each hydrogen and Q a --(CH.sub.2).sub.8 -- group (compound B).
By halogen in the case of the meaning of X and Y, respectively, is to be understood fluorine, chlorine or bromine, especially chlorine or bromine.
Cycloalkyl rings are carbocycli
REFERENCES:
patent: 4908385 (1990-03-01), Bar-Tana et al.
Doerge Liesel
Pill Johannes
Stegmeier Karlheinz
Boehringer Mannheim GmbH
Cooney Jr. John M.
Seidleck James J.
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