Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1995-03-17
1997-08-05
Bleutge, John C.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
514314, 546157, A61K 3147
Patent
active
056543174
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
This invention relates to an antiarrhythmic agent, more particularly to an antiarrythmic agent comprising as an active ingredient a carbostyril derivative of the following formula: ##STR2## wherein R.sub.1 is hydrogen atom or a lower alkyl group, and R.sub.2 is a phenyl-lower alkyl group which has optionally 1 to 3 substituents of a lower alkoxy group on the phenyl ring, or a pharmaceutically acceptable salt thereof.
BACKGROUND ART
The carbostyril derivatives of the formula (1) and their salts are known and disclosed, for example, in EP-A-0355583 and U.S. Pat. No. 5,053,514, wherein it is disclosed that these compounds have myocardial contract increasing activity (i.e. positive inotropic activity), coronary blood flow increasing activity, hypotensive activity, an activity of inhibiting blood vessel contract induced by norepinephrine, and antiinflammatory activity and are useful as cardiotonics for the treatment of heart diseases, hypotensives and antiinflammtory. It has also been disclosed in EP-A-0531548 that these compounds have platelet aggregation inhibitory activity, phosphodiesterase inhibitory activity and cerebral blood flow increasing activity and are useful as an agent for treating thrombosis and as a phosphodiesterase inhibitor.
DISCLOSURE OF THE INVENTION
The present inventors have studied on the pharmacological activities and utilities of these carbostyril derivatives and salts thereof and have found that these compounds show excellent antiarrhythmic activity and are useful as an antiarrhythmic agent.
An object of the invention is to provide a novel antiarrhythmic agent. Another object of the invention is to provide a new use of the known carbostyril derivatives of the formula (1) and their salts as an antiarrhythmic agent. A further object is to provide a method for the treatment of arrhythmia by administering an effective amount of the carbostyril derivative (1) or a salt thereof to the subject suffering from arrhythmia.
The each group in the formula (1) denotes as follows.
The "lower alkyl group" denotes a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, tert-butyl, pentyl, hexyl, and the like.
The "lower alkoxy group" denotes a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, tert-butoxy, pentyloxy, hexyloxy, and the like.
The "phenyl-lower alkyl group which has optionally 1 to 3 substituents of a lower alkoxy group on the phenyl ring" denotes a phenylalkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms and which has optionally 1 to 3 substituents of a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms on the phenyl ring, such as benzyl, 2-phenylethyl, 1-phenylethyl, 3-phenylpropyl, 4-phenylbutyl, 1,1-dimethyl-2-phenylethyl, 5-phenylpentyl, 6-phenylhexyl, 2-methyl-3-phenylpropyl, 2-(3-methoxyphenyl)ethyl, 1-(4-methoxyphenyl)ethyl, 2-methoxybenzyl, 3-(2-ethoxyphenyl)propyl, 4-(3-ethoxyphenyl)butyl, 1,1-dimethoxy-2-(4-ethoxyphenyl)ethyl, 5-(4-isopropoxyphenyl)pentyl, 6-(4-hexyloxyphenyl)hexyl, 3,4-dimethoxybenzyl, 3,4,5-trimethoxybenzyl, 2,5-dimethoxybenzyl, and the like.
Among the carbostyril derivatives of the formula (1), basic compounds can easily form a salt with conventional pharmaceutically acceptable acids. These acids include, for example, inorganic acids such as sulfuric acid, nitric acid, hydrochloric acid, phosphoric acid, hydrobromic acid, etc., and organic acids such as acetic acid, p-toluenesulfonic acid, ethanesulfonic acid, oxalic acid, maleic acid, fumaric acid, malic acid, tartaric acid, citric acid, succinic acid, benzolic acid, etc. Besides, among the carbostyril derivatives of the formula (1), acidic compounds can easily form a salt with conventional pharmaceutically acceptable basic compounds. These basic compounds include, for example, sodium hydroxide, potassium hydroxide, calcium hydroxide, sodium carbonate, pota
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Fujioka Takafumi
Teramoto Shuji
Tominaga Michiaki
Yabuuchi Yoichi
Bleutge John C.
Harrison Robert H.
Otsuka Pharmaceutical Company Limited
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