Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Patent
1996-08-08
1998-08-25
Henley, III, Raymond
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
A61K 31495
Patent
active
057983577
DESCRIPTION:
BRIEF SUMMARY
This application is a 571 of PCT/JP95/00244 filed Feb. 20, 1995.
1. Technical Field
The present invention relates to an agent for the prophylaxis and treatment of thromboxane A.sub.2 -mediated diseases, which comprises a pyridazinone compound or a pharmacologically acceptable salt thereof as an active ingredient, particularly to a thromboxane A.sub.2 synthetase inhibitor.
2. Background Art
Thromboxane A.sub.2 (TXA.sub.2) is mainly produced and released from platelets, and shows strong platelet aggregating action and vasopressing action. There are many reports with regard to the pathophysiological role thereof. The production of TXA.sub.2 has been found to be accelerated in the diseases such as arteriosclerosis, diabetes, ischemic heart diseases, pulmonary diseases, hypertension, shock, Kawasaki disease and alcoholic liver disease, thus indicating a high probability of TXA.sub.2 being involved in the onset and aggravation of these diseases. For the improvement of these diseases, TXA.sub.2 synthetase inhibitors and TXA.sub.2 antagonists such as imidazole derivatives, pyridine derivatives and imidazopyridine derivatives have been developed. However, an agent for the prophylaxis and treatment of TXA.sub.2 -mediated diseases, which has more superior effects, has beed desired.
It has been already known that pyridazinone compounds have platelet aggregation inhibitory action, cardiotonic action, vasodilating action and anti-SRS-A (Slow Reacting Substances of Anaphylaxis) action (WO91/16314, U.S. Pat. No. 5,202,323, EP-A-482208).
DISCLOSURE OF THE INVENTION
It has now been found that said pyridazinone compounds and pharmacologically acceptable salts thereof have an action heretofore not known, namely, prophylactic and therapeutic activities against TXA.sub.2 -mediated diseases, particularly, TXA.sub.2 synthetase inhibitory action.
It is therefore an object of the present invention to provide an agent for the prophylaxis and treatment of TXA.sub.2 -mediated diseases, by using a pyridazinone compound, particularly a TXA.sub.2 synthetase inhibitor.
According to the present invention, there is provided an agent for the prophylaxis or treatment of TXA.sub.2 -mediated diseases, particularly a TXA.sub.2 synthetase inhibitor, which comprises, as an active ingredient, a pyridazinone compound of the formula (I) ##STR2## wherein R.sup.1, R.sup.2 and R.sup.3 are each independently a hydrogen atom or a lower alkyl, X is a halogen atom, a cyano or a hydrogen atom, Y is a halogen atom, a trifluoromethyl or a hydrogen atom and A is a C.sub.1 -C.sub.8 alkylene optionally substituted by hydroxyl, or a pharmacologically acceptable salt thereof.
The symbols used in the present specification are explained in the following.
The lower alkyl for R.sup.1, R.sup.2 and R.sup.3 may be linear or branched and has 1 to 6 carbon atoms, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, t-butyl, pentyl and hexyl.
Preferable R.sup.1 and R.sup.2 are each hydrogen atom, and preferable R.sup.3 is hydrogen atom or C.sub.1 -C.sub.4 alkyl.
The C.sub.1 -C.sub.4 alkyl for R.sup.3 is exemplified by methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl and t-butyl.
The halogen atom for X and Y is, for example, fluoro atom, chloro atom, bromo atom or iodo atom, with preference given to halogen atom for X, and halogen atom or hydrogen atom for Y.
The C.sub.1 -C.sub.8 alkylene for A, which is optionally substituted by hydroxyl, may be linear or branched and is exemplified by methylene, ethylene, propylene, butylene, pentylene, hexylene, heptylene, octylene, 2,2-dimethylethylene, 2,2-diethylethylene, 2,2-di-n-propylethylene, hydroxymethylene, 1-hydroxyethylene, 2-hydroxyethylene and 3-hydroxypropylene. Preferred is C.sub.1 -C.sub.5 alkylene optionally substituted by hydroxyl.
In the formula (I), the bonding site of methylene and pyridine ring is not particularly limited. Preferable site is the 3-position relative to the nitrogen atom on the pyridine ring.
Y may be substituted at any position on the benzene ring, with preferen
Ikegawa Ruriko
Imada Teruaki
Nakamura Norifumi
Tanikawa Keizo
Tsuruzoe Nobutomo
Henley III Raymond
Nissan Chemical Industries Ltd.
The Green Cross Corporation
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