Blood Pressure

Agent for treating high blood pressure and cardiac insufficiency

Blood Pressure Abstract
The use of a compound of formula ##STR1## wherein the substituents are defined herein and the physiologically acceptable acid addition salts thereof for treating high blood pressure and cardiac insufficiency.

Blood Pressure Claims
What is claimed is:

1. A method of treating cardiac insufficiency in a warm-blooded animal which comprises administering to said animal a therapeutically effective amount of a compound of formula ##STR4## wherein A is a --CH.sub.2 --CH.sub.2 --, --CH.dbd.CH--, ##STR5## wherein R.sub.7 is an alkyl group having 1 to 3 carbon atoms, and B is a methylene or carbonyl group or

A is a --CO--CO-- group and B is a methylene group,

E is an ethylene, n-propylene or n-butylene group optionally substituted by an alkyl group with 1 to 3 carbon atoms, an n-propylene group substituted by a hydroxy group in the 2 position or an n-butylene group substituted by a hydroxy group in the 2 or 3 position,

G represent a methylene or ethylene group optionally substituted by an alkyl group with 1 to 3 carbon atoms,

R.sub.1 and R.sub.2, which may be identical or different, are hydroxy groups, alkyl, alkoxy or phenylalkoxy groups in which the alkyl moiety may contain from 1 to 3 carbon atoms, or one of the groups R.sub.1 or R.sub.2 may also represent a hydrogen atom or R.sub.1 together with R.sub.2 is an alkylenedioxy group with 1 or 2 carbon atoms,

R.sub.3 and R.sub.4, which may be identical or different, are hydrogen or halogen atoms, hydroxy groups, alkyl or alkoxy groups each having 1 to 4 carbon atoms, trifluoromethyl or cyano groups or one of the groups R.sub.3 or R.sub.4 is a nitro group or R.sub.3 together with R.sub.4 is an alkylenedioxy group with 1 or 2 carbon atoms,

R.sub.5 is a hydrogen atom, an alkyl, hydroxy, alkoxy, amino, alkylamino, dialkylamino, alkanoylamino, alkoxycarbonylamino or bis(alkoxycarbonyl)amino group wherein the alkyl part may contain from 1 to 3 carbon atoms, or a methylamino or ethylamino group substituted by a trifluoromethyl group, and

R.sub.6 is a hydrogen atom, an alkyl, phenylalkyl, alkanoyl or alkoxycarbonyl group in which the alkyl moiety may contain from 1 to 3 carbon atoms or an alkylene group with 3 to 5 carbon atoms.

and the physiologically acceptable acid addition salts thereof with inorganic or organic acids.

2. The method as recited in claim 1, characterized in that 1,3,4,5-tetrahydro-7,8-dimethoxy-3-[3-[[2-(3,4-dimethoxyphenyl)ethyl]methy l]amino]propyl]-2H-3-benzazepin-2-one or one of the physiologically acceptable acid addition salts thereof is administered.

3. The method as recited in claim 2, characterized in that the hydrochloride is administered as the acid addition salt.

Blood Pressure Description
EP-B-0.065.229 describes the compound of formula ##STR2## wherein

A represents a --CH.sub.2 --CH.sub.2 --, --CH.dbd.CH--, ##STR3## wherein R.sub.7 represents an alkyl group having 1 to 3 carbon atoms, and B represents a methylene or carbonyl group or

A represents a --CO--CO-- group and B represents a methylene group,

E represents an ethylene, n-propylene or n-butylene group optionally substituted by an alkyl group with 1 to 3 carbon atoms, an n-propylene group substituted by a hydroxy group in the 2 position or an n-butylene group substituted by a hydroxy group in the 2 or 3 position,

G represents a methylene or ethylene group optionally substituted by an alkyl group with 1 to 3 carbon atoms,

R.sub.1 and R.sub.2, which may be identical or different, represent hydroxy groups, alkyl, alkoxy or phenylalkoxy groups in which the alkyl moiety may contain from 1 to 3 carbon atoms, or one of the groups R.sub.1 or R.sub.2 may also represent a hydrogen atom or R.sub.1 together with R.sub.2 represents an alkylenedioxy group with 1 or 2 carbon atoms,

R.sub.3 and R.sub.4, which may be identical or different, represent hydrogen or halogen atoms, hydroxy groups, alkyl or alkoxy groups each having 1 to 4 carbon atoms, trifluoromethyl or cyano groups or one of the groups R.sub.3 or R.sub.4 may also represent a nitro group or R.sub.3 together with R.sub.4 represents an alkylenedioxy group with 1 or 2 carbon atoms,

R.sub.5 represents a hydrogen atom, an alkyl, hydroxy, alkoxy, amino, alkylamino, dialkylamino, alkanoylamino, alkoxycarbonylamino or bis(alkoxycarbonyl)amino group wherein the alkyl part may contain from 1 to 3 carbon atoms, or a methylamino or ethylamino group substituted by a trifluoromethyl group, and

R.sub.6 represents a hydrogen atom, an alkyl, phenylalkyl, alkanoyl or alkoxycarbonyl group in which the alkyl moiety may contain from 1 to 3 carbon atoms, or an alkylene group with 3 to 5 carbon atoms.

and the acid addition salts thereof, particularly the physiologically acceptable acid addition salts thereof with inorganic or organic acids, and the specification points out that this compound and the acid addition salts thereof have valuable pharmacological properties, e.g. a long-lasting heart rate lowering effect and the effect of reducing the O.sub.2 requirement of the heart.

The compounds have therefore been developed as novel substances which lower heart rate by acting directly on the sinoatrial node. As a result, the substances have anti-ischaemic properties, i.e. in addition to lowering the myocardial energy consumption by the heart rate they simultaneously increase the oxygen supply by extending the diastole. Pharmacological investigations have shown that the substances do not affect either inotropy or blood pressure or the AV transmission. Experiments on animals have shown an additional so-called myocardioprotective effect. Thus, the substances appear to be suitable for the treatment of stable coronary heart disease.

Tests on humans have surprisingly shown that the substances have valuable hypotensive properties.

The invention therefore relates to the use of the compounds of general formula I and the acid addition salts thereof, particularly the physiologically acceptable acid addition salts thereof with inorganic or organic acids, for treating high blood pressure and/or cardiac insufficiency.

The invention further relates to the use of these compounds and the acid addition salts thereof for the manufacture of a pharmaceutical preparation for the treatment of high blood pressure and/or cardiac insufficiency.