Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1994-10-27
1996-11-19
Rotman, Alan L.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
546 89, 546 90, A61K 3144, C07D49104
Patent
active
055763243
DESCRIPTION:
BRIEF SUMMARY
CROSS REFERENCE
This application is a 371 of PCT/JP93/00566, filed Apr. 28, 1993 and published as WO93/22317 Nov. 11, 1993.
TECHNICAL FIELD
The present invention relates to novel quinoline derivatives and medicinally acceptable salts thereof, which have pharmaceutical actions including positive inotropic action, antiarrhythmic action and vasodilating action. The present invention also relates to use of the compounds as medicines.
BACKGROUND ART
Congestive heart failure is a disease in which cardiac output deteriorates because of the malfunction of the heart, outputting only insufficient blood supply for the metabolism of tissue. Recently, J. N. Cohn has described the congestive heart failure as a syndrome caused by failure of the function of the heart which is accompanied by (1) deterioration of motor tolerance capacity, (2) multiple ventricular arrhythmia, and (3) signs indicating unfavorable symptoms (J. N. Cohn: Circulation 78, 1099 (1988)).
To ameliorate the above symptom-complex, diuretic agents, vasodilators, and cardiac tonics such as digitalis have conventionally been employed.
These days, digitalis agents are the most common cardiac tonics. Digoxin, one of the digitalis components, is known to promote the ejection of the heart, thereby preventing the cardiac insufficiency from aggravated. Digoxin has also remarkable advantages in that it lowers the cardiac rate, its effects last long, it does not have drug resistance, and it can be orally dosed. On the other hand, since the effective blood level of digoxin is close to its toxic level, it sometimes induces arrhythmia. Therefore, oral preparations of non-glycoside cardiac tonics have become of interest and, active studies are being made recently.
Accordingly, an object of the present invention is to provide a compound useful for the treatment of heart diseases which is free from the above mentioned drawbacks, and which has positive inotropic action, antiarrhythmic action and vasodilating action.
Under the above mentioned circumstances, the inventors of the present invention have synthesized many compounds, and have carried out screening of the compounds in view of the positive inotropic action, antiarrhythmic action and vasodilating action, and as a result, have found that the novel quinoline derivatives represented by the following formula (1) or their medicinally acceptable salts are suited for the above-mentioned purposes and are useful as medicines for the treatment of heart diseases, leading to completion of the invention.
DISCLOSURE OF THE INVENTION
The present invention provides quinoline derivatives of the following formula (1) and medicinally acceptable salts thereof: ##STR2## [wherein ring A: a furan ring, a dihydrofuran ring, or a dioxolane ring; R.sup.1 : hydroxy, carboxy, alkoxycarbonyl, carbamoyl, alkenyl, formyl, cyano, alkyl which may optionally have a substituent, or a group ##STR3## (wherein R.sup.9 : amino or alkyl, and R.sup.10 : hydrogen or hydroxy); R.sup.2 : same or different from each other, and represent hydrogen, alkyl which may optionally have a substituent, alkenyl, acyl, or hydroxy; hydrogen, halogen, alkyl which may optionally have a substituent, amino which may optionally have a substituent, alkoxy, alkylthio, carboxy, alkoxycarbonyl, acyl, carbamoyl, cyano, or nitro; represent hydrogen or alkyl; ].
Another object of the present invention is to provide a use of the quinoline derivatives represented by formula (1) and their medicinally acceptable salts.
A further object of the present invention is to provide a therapeutic method for heart diseases characterized by administering the quinoline derivatives represented by formula (1) or their medicinally acceptable salts to a patient suffering from a heart disease.
A still further object of the present invention is to provide a medicine for heart diseases which comprise, as an active component, a quinoline derivative represented by formula (1) or a medicinally acceptable salt thereof.
The quinoline derivatives of formula (1) and their medicinally acceptable salts
REFERENCES:
Chemical Abstracts, vol. 106, No. 21, May 25, 1987, AN 176374w, JP-A-61 267588, Nov. 27, 1986, p. 728.
Kawada Mitsuo
Kitamura Takahiro
Kurihara Yuji
Kyotani Yoshinori
Ohgiya Tadaaki
Kowa Co. Ltd.
Rotman Alan L.
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