Boehringer Mannheim Gmbh

Sb Pharmco Puerto Rico Inc.

Boehringer Mannheim Pharmaceuticals Corporation - Smithkline Beecham

Boehringer Mannheim Pharmaceuticals Corporation Smith Kline Corporation

Gisbert Sponer

Wolfgang Kampe

Karl Dietmann

Max Thiel

Walter-Gunar Friebe

Kurt Stach

Fritz Wiedemann

Alfred Mertens

Klaus Strein

Egon Roesch

Bernd Muller-Beckmann

Wolfgang Von Der Saal

Wolfgang Bartsch

Ernst-Christian Witte

Robert Ruffolo, Jr

Christos Tsaklakidis

Herbert Leinert

Kurt Stach, Deceased

Helmut Michel

Jens-Peter Holck

Carl H Ross

Neil Howard Shusterman

Mary Ann Lukas-Laskey

Jurgen Engel

Bernhard Kutscher

Wolfgang Schaumann

Otto-Henning Wilhelms

Werner Winter

Franz Braun

Michael Nelboeck-Hochstetter

Roland Ofenloch

By Werner Plattner, Administrator

By Werner Plattner, Executor

Georg Niebch

Erika Von Mullendorff

Harald D Borbe-Volmer

Fritz Wiedemann, Deceased

Karl Dietmann, Deceased

Ulrich Reicke

Neil Shusterman

Marianne Siebert-Weigel

A method of treatment using a compound of Formula I:wherein:

Method of treatment for decreasing mortality resulting from congestive heart failure

Use of carbazole compounds for the treatment of congestive heart failure

A method of treatment using a compound of Formula I: ##STR1## wherein: R.sub.1 is hydrogen, lower alkanoyl of up to 6 carbon atoms or aroyl selected from benzoyl and naphthoyl;

Method of treatment for decreasing mortality resulting from congestive

The present invention provides compounds of the general formula: ##STR1## wherein R.sub.1 is a hydroxyl group or a methoxy radical, R.sub.2 is a hydrogen atom or a hyroxyl group and R.sub.3 is a hydrogen atom or a hydroxyl group, with the proviso that R.sub.2 and R.sub.3 are not simultaneously hydrogen atoms when R.sub.1 is a methoxy radical; and the pharmacologically acceptable salts thereof. The present invention also provides processes for the preparation of these compounds and pharmaceutical compositions containing them.

Piperazine derivatives, uses thereof and pharmaceutical compositions

Naftopidil,1-(2-methoxyphenyl)-4-[3-(naphth-1-yloxy)-2-hydroxypropyl)]-pipe razine, or of a salt thereof, is effective in the treatment of dysuria, particularly in causes of prostatic hypertrophy.

Method for treating dysuria using naftopidil

The new pyrrolobenzimidazoles according to the present invention are compounds of the general formula: ##STR1## wherein R.sub.1 is a hydrogen atom or an alkyl, alkenyl or cycloalkyl radical, R.sub.2 is a hydrogen atom, an alkyl or alkenyl radical or a cyano group or a carbonyl group substituted by a hydroxyl or hydrazino group or by an alkyl, alkoxy, amino, alkylamino or dialkylamino group or together with R.sub.1 represents a cycloalkylene radical or R.sub.1 and R.sub.2 together form an alkylidene or cycloalkylidene radical, X is a valency bond, a C.sub.1 -C.sub.4 alkylene radical or a vinylene radical, T is an oxygen or sulphur atom and Py is a 2-, 3- or 4-pyridyl radical which optionally carries an oxygen atom on the ring heteroatom and/or can be substituted one or more times by alkyl, alkoxy, hydroxyl, cyano or nitro, as well as by halogen; the tautomers thereof and the physiologically acceptable salts thereof with inorganic and organic acids.

Certain pyridinoylamino-indolin-2-one derivatives

The present invention provides compounds of the general formula: ##STR1## wherein R.sub.1 is a straight-chained or branched C.sub.1 -C.sub.12 -alkyl radical which can be substituted by phenyl, naphthyl or a C.sub.3 -C.sub.7 -cycloalkyl radical; a straight-chained or branched C.sub.2 -C.sub.6 -alkenyl radical which can be substituted by a C.sub.3 -C.sub.7 -cycloalkyl radical or a phenyl or naphthyl radical; a C.sub.3 -C.sub.7 -cycloalkyl radical or a mono- or bicyclic aromatic radical which is unsubstituted or substituted one or more times, the substituents being C.sub.1 -C.sub.4 -alkyl, C.sub.1 -C.sub.4 -alkoxy, carboxyl or carbethoxy, R.sub.2 and R.sub.3, which can be the same or different, are straight-chained or branched, saturated or unsaturated C.sub.1 -C.sub.6 -alkyl radicals which are optionally substituted by hydroxyl, C.sub.1 -C.sub.3 -alkoxy or C.sub.1 -C.sub.3 -alkoxy-C.sub.1 -C.sub.3 -alkoxy or, together with the nitrogen atom to which they are attached, form a saturated or unsaturated ring which can contain further heteroatoms and is optionally substituted by a lower alkyl or lower alkoxy radical or by an oxygen atom, A is a valency bond or a straight-chained or branched alkylene radical containing up to 6 and preferably up to 3 carbon atoms, R.sub.4 is a mono- or bicyclic aromatic or heteroaromatic radical which is unsubstituted or substituted one or more times, whereby the substituents are alkyl, C.sub.2 -C.sub.6 -alkenyl, alkoxy, C.sub.2 -C.sub.6 -alkenyloxy, hydroxyalkyl, C.sub.2 -C.sub.6 -alkylenedioxy, hydroxyalkoxy, alkoxyethoxy, alkylamino, dialkylamino, alkoxycarbonylethyloxy, alkylthio, alkylsulphinyl, alkylsulphonyl, alkylsulphonyloxy, carboxyl, alkoxycarbonyl, aminocarbonyl, mono- or dialkylaminocarbonyl, haloalkyl or cyano, as well as halogen atoms, such as chlorine, bromine or fluorine, X is a valency bond or a straight-chained or branched, saturated or unsaturated hydrocarbon radical containing up to 6 carbon atoms, Y is a valency bond or an oxygen atom and R.sub.5 is a C.sub.3 -C.sub.7 -cycloalkyl radical or a mono- or bicyclic aromatic or heteroaromatic radical which is unsubstituted or substituted one or more times, the substituents being alkyl, alkoxy, C.sub.2 -C.sub.6 -alkenyloxy, aralkoxy, hydroxyl, hydroxyalkoxy, alkoxyalkoxy, alkoxycarbonylalkoxy, C.sub.1 -C.sub.2 -alkenylenedioxy, dialkylamino, alkylthio, alkylsulphinyl, alkyl-sulphonyl, alkylsulphonyloxy, hydroxyalkyl, carboxyl, alkoxycarbonyl, aminocarbonyl, mono- or dialkylaminocarbonyl or cyano, as well as halogen atoms, such as chlorine, bromine or fluorine, with the proviso that Y cannot be an oxygen atom when X is a valency bond and that when R.sub.1 is a saturated hydrocarbon radical, X must be a radical with at least 2 carbon atoms; as well as the pharmacologically acceptable salts thereof and the optical isomers thereof. The present invention also provides processes for the preparation of these 1,2-diamino compounds and pharmaceutical compositions containing them.

1,2-diamino compounds, processes for their preparation and

Compounds are disclosed, including 2-diethylamino-3-isobutoxy-N-phenyl-N-2-furanyl-methyl-propylamine and compounds of the formula: ##STR1## wherein R.sub.1 is an iso-C.sub.4 -C.sub.6 -alkyl radical; A is a valency bond or a straight-chained or branched alkyl radical containing up to 6 carbon atoms; R.sub.4 is a phenyl radical which is unsubstituted or substituted one or more times by C.sub.1 -C.sub.6 -alkyl, C.sub.2 -C.sub.6 -alkenyl, C.sub.1 -C.sub.3 -alkoxy, C.sub.2 -C.sub.6 -alkenyloxy, hydroxy-C.sub.1 -C.sub.6 -alkyl, C.sub.2 -C.sub.6 -alkylenedioxy, hydroxy-C.sub.1 -C.sub.3 -alkoxy, C.sub.1 -C.sub.3 -alkoxy-C.sub.1 -C.sub.3 -alkoxy, C.sub.1 -C.sub.6 -alkylamino, di(C.sub.1 -C.sub.6 -alkyl)amino, C.sub.1 -C.sub.3 -alkoxycarbonyl-C.sub.1 -C.sub.3 -alkoxy, C.sub.1 -C.sub.6 -alkylthio, C.sub.1 -C.sub.6 -alkylsulphinyl, C.sub.1 -C.sub.6 -alkylsulphonyl, C.sub.1 -C.sub.6 -alkylsulphonyloxy, carboxyl, C.sub.1 -C.sub.3 -alkoxycarbonyl, aminocarbonyl, mono- or di(C.sub.1 -C.sub.6 -alkyl)aminocarbonyl, halo-C.sub.1 -C.sub.6 -alkyl, cyano, or halogen; and R.sub.5 is a benzyl radical substituted at least once by C.sub.1 -C.sub.3 -alkoxy. The compounds are useful for the treatment of heart circulatory diseases.

1,2-diamino compounds, process for their preparation and pharmaceutical

The present invention provides indole derivatives of the general formula: ##STR1## wherein R.sub.1 is a hydrogen atom or an alkyl, alkenyl, cycloalkyl, cycloalkenyl, carboxyl, cyano, alkylcarbonyl, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl or aryl radical, R.sub.2 is a hydrogen atom or an alkyl, trihalogenomethyl, hydroxyl, cycloalkyl, cyano, carboxyl, alkoxycarbonyl, alkylcarbonyl, aminocarbonyl, alkylaminocarbonyl or dialkylaminocarbonyl radical; R.sub.2 is a heterocyclic five-membered ring containing 1 to 4 heteroatoms or a heterocyclic six-membered ring containing 1 to 5 heteroatoms, the heteroatoms of the five- and six-membered rings being the same or different and being nitrogen, oxygen or sulphur and one or more of the nitrogen atoms optionally carrying an oxygen atom, the said five- and six-membered rings optionally being substituted by one or more alkyl, alkoxy, alkylthio, oxo, hydroxyl, nitro, amino, halogen or cyano groups; or R.sub.2 is ##STR2## the tautomers thereof and the physiologically acceptable salts thereof with inorganic and organic acids. The present invention also provides processes for the preparation of these compounds and pharmaceutical compositions containing them. Furthermore, the present invention provides intermediates of the general formula: ##STR3## in which R.sub.1, R.sub.2, A and X have the same meanings as above, and processes for the preparation of these intermediates.

Heterocyclic-substituted indoles and pharmaceutical compositions

The present invention provides pyridazinone derivatives of the general formula: ##STR1## wherein Het is a mono- or bicyclic heterocycle with one or two nitrogen atoms, B-C is a --CHR.sub.1 --CH.sub.2 --, --CR.sub.1 .dbd.CH--, --CHR.sub.1 --O--, --O--CHR.sub.1 --, --CHR.sub.1 --NH-- or --NH--CHR.sub.1 -- group, R.sub.1 being a hydrogen atom or an alkyl radical, and A is an amiono, alkylcarbonylamino, aminocarbonylamino, aminothiocarbonylamino, alkylaminothiocarbonylamino, alkylamionocarbonylamino, N'-cyanoguanidino or N'-cyano-N'-alkylguanidino group, a substituted phenyl ring or heterocycle attached via a nitrogen or sulphur atom, or a mono- or bicyclic substituted heterocycle with 1 to 3 nitrogen atoms, one ring nitrogen atom being directly attached to Het; as well as the physiologically acceptable salts thereof. The present invention also provides processes for the preparation of these pyridazinone drivatives and pharmaceutical compositions containing them for the treatment of heart and circulatory diseases.

Pyridazinone derivatives, and pharmaceutical compositions containing them

The present invention provides new tricyclic benzotriazoles of the general formula: ##STR1## wherein Z is a hydrogen atom or an acyl radical, Y is an oxygen or sulphur atom or two hydrogen atoms and X is an oxygen or sulphur atom or a &gt;CR.sub.1 R.sub.2 or &gt;NR.sub.3 group, R.sub.1 is a hydrogen atom or an alkyl, alkenyl or cycloalkyl radical, R.sub.2 is a hydrogen atom or an alkyl, alkenyl or cyano group or a carbonyl group substituted by a hydroxyl, alkyl, alkoxy, amino, alkylamino, dialkylamino or hydrazino group or R.sub.2, together with R.sub.1, represents a cycloalkylene radical or R.sub.1 and R.sub.2 together form an alkylidene or cycloalkylidene radical and R.sub.3 is a hydrogen atom or an alkyl radical; the tautomers thereof and the physiologically acceptable acid-addition salts thereof with inorganic and organic acids. The present invention also provides processes for the preparation of these tricyclic benzotriazoles and pharmaceutical compositions containing them for the treatment of heart and circulatory diseases.

Tricyclic benzotriazoles, processes for the preparation thereof and

Pyrrolobenzimidazoles, processes for the preparation thereof and pharmaceutical compositions thereof for the treatment of coronary insufficiencies, cardiac failure, blood circulatory disturbances and occlusive diseases. The new pyrrolobenzimidazoles are of the formula ##STR1## wherein R.sub.1 is hydrogen, alkyl, alkenyl or cycloalkyl, R.sub.2 is hydrogen, alkyl, alkenyl, cyano or a substituted carbonyl or R.sub.1 and R.sub.2 together represent cycloalkylene or form alkylidene or cycloalkylidene, X is a valency bond, C.sub.1 -C.sub.4 alkylene or vinylene, T is oxygen or sulphur and Py is pyridyl or substituted pyridyl and including the tautomers thereof and the physiologically acceptable salts thereof.

Pyrrolobenzimidazoles for treating heart or circulatory diseases

The present invention provides aryloxypropanolamines of the general formula: ##STR1## wherein R.sub.1, R.sub.2, R.sub.3 and R.sub.4, which may be the same or different, are hydrogen or halogen atoms or lower alkyl, cyano, carboxamide, hydroxyl, lower acyloxy, lower alkoxy, lower alkenyloxy or aryl lower alkoxy radicals, R.sub.5 and R.sub.6, which may be the same or different, are hydrogen atoms or lower alkyl radicals, X is a straight or branched alkylene chain containing 2 to 6 carbon atoms, A is a mono-, bi- or tricyclic heteroaromatic or hydroheteroaromatic radical or, when at least one of the symbols R.sub.1, R.sub.2, R.sub.3 and R.sub.4 is other than a hydrogen atom, may also be a phenyl radical, with the proviso that when A is a uracil-6-yl radical, the 5-position of the uracil moiety does not contain a hydrogen atom, R.sub.7, R.sub.8, R.sub.9, R.sub.10 and R.sub.11, which may be the same or different, are mono- or divalent substituents selected from hydrogen, halogen, notro, hydraxylamino, amino, lower acylamino, lower alkylamino, di-(lower alkyl)-amino, hydroxyethylamino, di-(hydroxyethyl)-amino, hydroxyl, lower alkoxy, allyloxy, methoxy lower alkoxy, cyano, carboxamido, carboxy, lower alkoxycarbonyl, hydroxymethyl, lower alkoxymethyl, halomethyl, aminomethyl, lower acylaminomethyl, halomethyl, aminomethyl, lower acylaminomethyl, di(lower alkyl)-aminomethyl, pyrrolidinomethyl, piperidinomethyl, di-(hydroxyethyl)-amino, hydroxyl, lower alkoxy, allyloxy, methoxy lower alkoxy, cyano, carboxamido, carboxy, lower alkoxycarbonyl, hydroxymethyl, lower alkoxymethyl, halomethyl, aminomethyl, lower acyaminomethyl, di-(lower alkyl)-aminomethyl, pyrrolidinomethyl, piperidinomethyl, di-(hydroxyethyl)-aminomethyl, morpholinomethyl, piperazinomethyl, 4-lower acylpiperazinomethyl, 4-lower alkylpiperazinomethyl, lower alkyl, lower alkenyl, 2-cyanoethyl, 2-hydroxyethyl, phenyl lower alkyl and phenyl, the phenyl radicals being optionally substituted with 1 or 2 hydroxyl or methoxy radicals, or from oxygen or sulphur; the optically-active forms and the racemic mixtures thereof, and the pharmacologically compatible salts thereof. The present invention also provides processes for the preparation of these compounds and pharmaceutical compositions containing them. These compounds are useful for the prophylaxis and combatting of cardiac and circulatory diseases.

Cardioactive pyrazole and imidazole aryloxypropanolamines

Carbazolyl-(4)-oxypropanolamine compounds of the formula ##STR1## wherein R.sub.1 is hydrogen, lower alkanoyl or aroyl;

Carbazolyl-(4)-oxypropanolamine compounds and therapeutic compositions

The present invention provides aminopropanol derivatives of the general formula: ##STR1## wherein R.sub.1 is a hydrogen atom or a lower alkanoyl or an aroyl radical, R.sub.2 is a lower alkyl radical or a radical of the general formula: ##STR2## wherein X is a valency bond, a methylene group or an oxygen or sulphur atom, Ar is a monocyclic, carbo- or heterocyclic aryl radical, R.sub.6 and R.sub.7, which can be the same or different, are hydrogen atoms or lower alkyl radicals, R.sub.8 and R.sub.9, which can be the same or different, are hydrogen or halogen atoms, hydroxyl groups, lower alkanoyl radicals, alkenyl radicals, alkynyl radicals, alkyl radicals, lower alkoxy radicals, aralkoxy radicals, alkenyloxy radicals, alkynyloxy radicals, lower alkylthio radicals, aminocarbonyl radicals, aminosulphonyl radicals or acylamino radicals; or R.sub.2 is a 1,4-benzodioxan-2-ylmethyl radical, R'.sub.2 is a hydrogen atom or a benzyl radical, R.sub.3 is a carboxyl group or a lower alkoxycarbonyl, aminocarbonyl, cyano, oximinomethyl, formyl, hydroxymethyl or lower alkoxycarbimidoyl radical, R.sub.4 is a hydrogen atom or a lower alkyl radical or a --CH.sub.2 --O--R.sub.1 radical, R.sub.1 having the same meaning as above, and R.sub.5 is a hydrogen atom or a lower alkyl radical; the optionally-active forms and racemates thereof and the pharmacologically acceptable salts thereof. The present invention also provides processes for the preparation of these compounds and pharmaceutical compositions containing them. Furthermore, the present invention is concerned with the use of these compounds for the prophylaxis and treatment of heart and circulatory diseases.

3-Cyano-indoles as cardioselective agents

Growing community of inventors

Laudenbach, Germany

Gisbert Sponer