Ciba-geigy Corporation

Hans Kuhnis

Kurt Eichenberger

Franz Ostermayer

Herbert Schroter

Oswald Schier

Christian Egli

Bruno Kamber

Ernst Habicht

Markus Zimmermann

Thomas Leutert

Compounds of the formula ##STR1## in which R represents a carbocyclic or heterocyclic aryl radical, R.sub.1 represents lower alkyl, one of the groups R.sub.2 and R.sub.3 represents lower alkyl and the other represents lower alkyl, cyano aor amino, X represents oxygen or the group --NH--, Alk.sub.1 represents lower alkylene or optionally substituted phenyl-lower alkylene, which separates the group X from the nitrogen atom by at least two carbon atoms, R.sub.4 represents hydrogen, lower alkyl or optionally substituted phenyl-lower alkyl, Z represents the group --(C.dbd.O)-- or a single bond, Alk.sub.2 represents lower alkylene which separates the groups Z and Y preferably by from 2 to 4 carbon atoms, Y represents the group --(C.dbd.O)-- and Ar.sub.1 represents a monocyclic, carbocyclic or heterocyclic aryl radical, and salts of such compounds having salt-forming properties, have cardiovascular properties, especially coronary dilatory and anti-hypertensive properties.

3,5-diacyl-2,6-dialkyl-4-aryl-1,4-dihydropyridines, their use, and

Compounds of the formula I ##STR1## in which n represents 1, 2 or 3, Ar represents a carbocyclic or heterocyclic aryl radical, Ac represents the acyl radical of an acid, Z represents a radical --OR.sub.7 or --NR.sub.8 R.sub.9, R.sub.1 represents hydrogen, unsubstituted or substituted lower alkyl, a carbocyclic or heterocyclic aryl radical or free, etherified or esterified hydroxy, R.sub.2 and R.sub.3, independently of one another, each represents hydrogen, unsubstituted or substituted lower alkyl, formyl or functionally modified formyl, carboxy or functionally modified carboxy, a carbocyclic or heterocyclic aryl radical or unsubstituted or mono- or di-substituted amino, R.sub.4 represents hydrogen or lower alkyl, R.sub.5 and R.sub.6, independently of one another, each represents hydrogen, unsubstituted or substituted lower alkyl or a carbocyclic or heterocyclic aryl radical, R.sub.7, R.sub.8 and R.sub.9, independently of one another, each represents hydrogen, unsubstituted or substituted alkyl or a carbocyclic or heterocyclic aryl radical; in which R.sub.1 and R.sub.2 together or R.sub.1 and R.sub.3 together may represent unsubstituted or substituted lower alkylene in which a carbon atom is optionally replaced by a hetero atom, in which R.sub.4 and R.sub.5 together, and likewise R.sub.5 and R.sub.6 together and/or R.sub.8 and R.sub.9 together, independently of one another, may represent unsubstituted or substituted lower alkylene in which a carbon atom may have been replaced by a hetero atom, optical isomers of compounds of the formula I, mixtures of these optical isomers and salts of such compounds that have a salt-forming grouping, are distinguished by cardiovascular, especially blood pressure-reducing, properties. They are manufactured in a manner known per se.

Dihydro pyridine compounds, compositions and use

The present invention relates to novel N-oxide compounds that have cardiovascular properties, especially antihypertensive activity, and that correspond to the formula ##STR1## in which Py represents an unsubstituted or substituted N-oxidopyridyl radical, R.sub.1 represents hydrogen or unsubstituted or substituted lower alkyl, one of the radicals R.sub.2 and R.sub.3 represents lower alkyl and the other represents hydrogen; lower alkyl; lower alkyl containing free, etherified or esterified hydroxy, oxo, functionally modified carboxy or free or substituted amino or imino; functionally modified carboxy; or free or substituted amino, it being possible for an amino group R.sub.2 or R.sub.3 to be bonded to a lower alkyl radical R.sub.1 or, if R.sub.2 or R.sub.3 represents, for example, hydroxy-lower alkyl, for this hydroxy-lower alkyl, together with the adjacent acyl radical Ac.sub.1 or Ac.sub.2, to form a 2-oxa-1-oxo-lower alkylene radical, the carbonyl group of which is bonded to the 3- or 5-ring carbon atom of the 1,4-dihydropyridine ring, and each of the groups Ac.sub.1 and Ac.sub.2 represents, independently of the other, the acyl radical of an acid, and salts of compounds of the formula I having salt-forming groups, processes for the manufacture of these compounds, the use of these compounds and their salts, and pharmaceutical preparations which contain these compounds and salts, as antihypertensive agents and coronary dilators for the treatment of cardiovascular conditions, such as hypertonia, vascular constrictions, Angina pectoris and cardiac insufficiency.

N-Oxide compounds useful in the treatment of cardiovascular ailments

Piperidines of the formula ##STR1## in which R.sub.1 is a substituted or unsubstituted heteroaryl radical, alk.sub.1 and alk.sub.2 independently of one another are lower alkylene radicals, each of which separates by 2 carbon atoms the nitrogen atom bonded thereto from the methane group bonded thereto, R.sub.2 is a free or acylated hydroxyl group, Ph is a substituted or unsubstituted o-phenylene radical, n is 0 or 1, R.sub.3 is a hydrogen atom, a lower alkyl radical or a hydroxyl group and R.sub.5 is a lower alkyl radical or a hydrogen atom, or R.sub.3 and R.sub.5 together are a second bond and R.sub.4 and R.sub.6 are each a hydrogen atom, or R.sub.4 together with R.sub.3 is an oxo group, R.sub.5 is a lower alkyl radical or a hydrogen atom and R.sub.6 is a hydrogen atom, or R.sub.6 together with R.sub.5 is an oxo group, R.sub.3 is a hydrogen atom, a lower alkyl radical or a hydroxyl group and R.sub.4 is a hydrogen atom, or salts thereof are antihypertensive and antiarrhythmic agents.

Piperidine derivatives

The invention relates to novel piperidino-propanols, especially 1-(3-heterocyclyloxy-2-hydroxy-propanol)-4-(N-diazcyclyl)-piperidines of the formula ##STR1## in which R.sub.1 is a substituted or unsubstituted heteroaryl radical, R.sub.2 is hydrogen or a substituted or unsubstituted aliphatic, cycloaliphatic, cycloaliphatic-aliphatic or araliphatic hydrocarbon radical or an acyl radical and alk is lower alkylene which separates the two nitrogen atoms from one another by 2 or 3 carbon atoms, or is a substituted or unsubstituted 1,2-phenylene radical, and salts thereof, as well as processes for their preparation, and also to pharmaceutical preparations containing these compounds and the use thereof, preferably in the form of pharmaceutical preparations as antihypertensive agents, antitachycardiac agents and .alpha.-sympathicolytic agents.

Piperidino-propanols

A process known per se for the manufacture of oxygenated N-aryl-diazacyclic compounds of the formula ##STR1## wherein each of R.sub.1 and R.sub.2 represents a substituted or unsubstituted aryl group and alk represents a lower alkylene group which separates both nitrogen atoms from each other by 2 or 3 carbon atoms, or salts thereof. The novel compounds can be used as antihypertensives, antitachycardiac agents and .alpha.-receptor blockers.

Oxygenated N-aryl-diazacyclic compounds

A process known per se for the manufacture of oxygenated N-aryl-diazacyclic compounds of the formula ##STR1## wherein EACH OF R.sub.1 and R.sub.2 represents a substituted or unsubstituted aryl group and alk represents a lower alkylene group which separates both nitrogen atoms from each other by 2 or 3 carbon atoms, or salts thereof. The novel compounds can be used as antihypertensives, antitachycardiac agents and .alpha.-receptor blockers.

Antihypertensive 1-substituted-4-(2-oxo-1-imidazolidinyl) piperidines

1-(3-Aryloxy-2-hydroxypropyl)-4-(1-oxoisoquinolino)-piperidines, e.g. those of the formula ##STR1## R' = H, alkanoylaminoethenyl, carbamoyl, alkanoyl, CN, alkoxycarbonylamino-lower alkyl, halo, OH, alkanoylamino, alkyl, alkoxy, alkenyl, alkenyloxy

4(2' Isoquinolin-1-one)piperidines

The present invention relates to 1,4-dihydropyridines of the formula I ##STR1## and their tautomers, wherein R.sub.1 represents an aryl radical, R.sub.2 and R.sub.3 independently of one another represents hydrogen or a hydrocarbon radical, R.sub.4 represents an alkyl, aryl or aralkyl radical, R.sub.5 denotes an alkoxy radical, which is optionally substituted by an amino group, or denotes an amino group and n is 1 or 2, especially to the 2,6-dimethyl-3-carbomethoxy-5-methylsulphonyl-4-(2-trifluoromethylphenyl)- 1,4-dihydro-pyridine and to the 2,6-dimethyl-3-carbomethoxy-5-methylsulphonyl-4-(2-nitrophenyl)-1,4-dihydr opyridine. They have an antihypertensive activity.

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Basel, Switzerland

Hans Kuhnis