Aniline derivatives and cardiotonic composition

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...

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544121, 544357, 544360, 544372, A61K 31495, C07D29510

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active

045857741

DESCRIPTION:

BRIEF SUMMARY
TECHNICAL FIELD

The present invention relates to novel aniline derivatives and their salts.


DISCLOSURE OF INVENTION

Compounds of the present invention are novel ones which have not been disclosed in any literature, and are represented by the following general formula, ##STR3## [wherein R.sup.0, R.sup.1 and R.sup.2 are the same or different and each are a hydrogen atom, a halogen atom, a nitro group, an amino group, a carboxy group, a cyano group, a hydroxy group, a sulfonamido group, a lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxy group, a lower alkanoyl group, a lower alkylamino group, a lower alkylthio group, a lower alkanoylamino group or a group of the formula ##STR4## (wherein, R.sup.5 and R.sup.6 are the same or different and each are a hydrogen atom, a lower alkyl group or a cycloalkyl group; or said R.sup.5 and R.sup.6 may form 5- or 6-membered saturated heterocyclic group together with the nitrogen atom adjacent thereto, or further with or without a nitrogen atom or oxygen atom); R.sup.3 is a cyano group, a nitro group, a halogen atom, a lower alkyl group or a lower alkoxy group; m is an integer of 1 to 3; R.sup.4 is a hydrogen atom or a lower alkyl group; A is a lower alkylene group; provided that when R.sup.3 is a lower alkoxy group, a halogen atom or a lower alkyl group; and when R.sup.0 is a hydrogen atom and further A is a methylene group, then R.sup.1 and R.sup.2 are the same or different and should not be hydrogen atoms, halogen atoms, lower alkyl groups or lower alkoxy groups; further when R.sup.3 is a lower alkoxy group, a halogen atom or a lower alkyl group, and R.sup.0 is a halogen atom, a lower alkyl group or a lower alkoxy group and A is a methylene group, then either one of R.sup.1 or R.sup.2 is a hydrogen atom and the other one should not be a halogen atom, a lower alkyl group or a lower alkoxy group.]


BEST MODE FOR CARRYING OUT THE INVENTION

Aniline derivatives and their salts represented by the general formula (1) are novel drugs and act directly to the heart, and have myocardial contraction increasing activity (positive inotropic activity) and coronary blood flow increasing activity, and thus they are useful as cardiotonics for curing various heart diseases such as acute left venticular heart failure, cardiogenic shock, low output heart failure syndrome and the like. Specifically, aniline derivatives and their salts represented by the general formula (1) of the present invention are characterized as their low toxicities to the heart, thus they have almost no heart beat increasing activity.
As to the lower alkoxycarbonyl group mentioned in the present specification, an alkoxycarbonyl group having 1 to 6 carbon atoms in the alkoxy moiety, such as methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, tert-butoxycarbonyl, pentyloxycarbonyl or hexyloxycarbonyl group or the like can be exemplified.
As to the lower alkoxy group mentioned in the present specification, an alkoxy group having 1 to 6 carbon atoms, such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, tert-butoxy, pentyloxy or hexyloxy group or the like can be exemplified.
As to the lower alkylene group mentioned in the present specification, an alkylene group having 1 to 6 carbon atoms, such as methylene, ethylene, trimethylene, 2-methyltrimethylene, tetramethylene, 1-methyltetramethylene, pentamethylene or hexamethylene group or the like can be exemplified.
As to the group of the formula ##STR5## (wherein R.sup.5 and R.sup.6 are the same or different, and each are a hydrogen atom, a lower alkyl group or a cycloalkyl group), there are exemplified such as carbamoyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, butylaminocarbonyl, tert-butylaminocarbonyl, pentylaminocarbonyl, hexylaminocarbonyl, dimethylaminocarbonyl, diethylaminocarbonyl, dipropylaminocarbonyl, diisopropylaminocarbonyl, dibutylaminocarbonyl, di-tert-butylaminocarbonyl, dipentylaminocarbonyl, dihexylaminocarbonyl, methylethylaminocarbonyl, methylpropylaminocarbon

REFERENCES:
patent: 3352866 (1967-11-01), Dornfeld
patent: 4223034 (1980-09-01), Hadley
Otto, "Chemical Abstracts", vol. 82, 1975, col. 43459s.
Munakata, et al., "Chemical Abstracts", vol. 95, 1981, col. 95:115751z.

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