Merck Patent Gesellschaft MIT Beschrankter Haftung

Hans-Jochen Schliep

Rochus Jonas

Hans J Enenkel

Klaus-Otto Minck

Hanns Wurziger

Hans-Eckart Radunz

Klaus Otto Minck

Michael Klockow

Hans-Joachim Enenkel

Michael Kloft

Michael Wolf

Dieter Orth

Werner Mehrhof

Juergen Harting

Karl-Heinz Becker

Ernst Schorscher

Karl Heinz Becker

Christoph Seyfried

Manfred Baumgarth

Joachim Gante

Hans-Adolf Kurmeier

Joachim Leibrock

Ingeborg Lues

Rolf Pohlke

Jurgen Harting

Wolf-Dietrich Weber

Helmut Muller-Calgan

Jaime Piulats

The present invention relates to thiadiazinones of the formula I ##STR1## having a phosphodiesterase-inhibiting action and which are suitable for combating cardiovascular and asthmatic disorders.

Thiadiazinones

Compounds of formula I ##STR1## in which R.sup.1 and R.sup.2 are each independently of one another H or A,

New 2-arylimidazopyridines of the general formula I ##STR1## wherein --A.dbd.B-- is (a) --CH.dbd.N-- or (b) N.dbd.CH--,

2-arylimidazopyridines

New salicylic acid derivatives of the general formula I ##STR1## in which R.sup.1 is H or CH.sub.3,

Salicylic acid derivatives

Thiadiazinones of the formula I ##STR1## wherein A is --CHR.sup.4 --CHR.sup.5 --, --CH.sub.2 --CR.sup.4 R.sup.5 --, --CR.sup.4 R.sup.5 --CH.sub.2 --, --CHR.sup.4 --CHR.sup.5 --CH.sub.2 --, --CHR.sup.4 --CH.sub.2 --CHR.sup.5 --, --CH.sub.2 --CHR.sup.4 --CHR.sup.5 --, --CR.sup.4 R.sup.5 --CH.sub.2 CH.sub.2 --, --CH.sub.2 --CR.sup.4 R.sup.5 --CH.sub.2 -- or --CH.sub.2 CH.sub.2 --CR.sup.4 R.sup.5 --,

2-Aryltetraazaindenes of the formula ##STR1## wherein --A-- is --N.dbd.CH--CN.dbd.N-- or --CH.dbd.N--N.dbd.CH--, Ar is unsubstituted phenyl or phenyl mono-, di- or tri-substituted by hydroxyl, mercapto, dialkylamino, trifluoromethyl and/or --Z--R groups, Z is --O--, --S-- or --SO-- and R is alkyl, alkenyl, alkynyl or cyanomethyl, the alkyl, alkenyl and alkynyl groups each having up to 5 C atoms, and their physiologically acceptable salts, exhibit blood pressure, myocardial contraction, and anti-ulcer activities.

Pharmaceutical compositions for treating ulcers containing

2-Aryltetraazaindenes of the formula ##STR1## wherein --A-- is --N.dbd.CH--CH.dbd.N-- or --CH.dbd.N--N.dbd.CH--, Ar is unsubstituted phenyl or phenyl mono-, di- or trisubstituted by hydroxyl, mercapto, dialkylamino, trifluoromethyl and/or --Z--R groups, Z is --O--, --S-- or --SO-- and R is alkyl, alkenyl, alkynyl or cyanomethyl, the alkyl, alkenyl and alkynyl groups each having up to 5 C atoms, and their physiologially acceptable salts, exhibit blood pressure, myocardial contraction, and anti-ulcer activities.

Pharmaceutical compositions containing 2-aryltetraazaindenes for

2-Aryltetraazaindenes of the formula ##STR1## wherein --A-- is --N.dbd.CH--CH.dbd.N-- or --CH.dbd.N--N.dbd.CH--, Ar is unsubstituted phenyl or phenyl mono-, di- or tri-substituted by hydroxyl, mercapto, dialkylamino, trifluoromethyl and/or --Z--R groups, Z is --O--, --S-- or --SO-- and R is alkyl, alkenyl, alkynyl or cyanomethyl, the alkyl, alkenyl and alkynyl groups each having up to 5 C atoms, and their physiologically acceptable salts, exhibit blood pressure, myocardial contraction, and anti-ulcer activities.

2-Aryltetraazaindenes for treating cardiac insufficiency

13-Thiaprostanoic acid derivatives of the general formula I ##STR1## wherein A is --CO-- or --CHOH--; B is --CH.sub.2 CH.sub.2 -- or --CH.dbd.CH--; Q is 1,4-phenylene or 1,4-naphthylene; R.sup.1 is H or OH; R.sup.2 is H or CH.sub.3 ; R.sup.3 is alkyl with 1-8 carbon atoms or alkyl with 1-8 carbon atoms substituted by (a) phenyl, (b) phenyl substituted by at least one of CH.sub.3, F, Cl, Br, OH, OCH.sub.3 or CF.sub.3 ; (c) phenoxy or (d) phenoxy substituted by at least one of CH.sub.3, F, Cl, Br, OH, OCH.sub.3 or CF.sub.3 ; and R.sup.4 is NH.sub.2, CH.sub.3, phenyl, p-acetylaminophenyl, p-benzoylaminophenyl or phenylamino. These compounds are useful for lowering blood pressure as well as for other pharmaceutical purposes. They also are useful intermediates for the preparation of other known pharmaceuticals such s the 13-thiaprostaglandins.

13-Thiaprostaglandin derivatives

Phenothiazine derivatives of the formula ##STR1## wherein R is H, F, Cl, Br, I, CH.sub.3, CF.sub.3, CN, CH.sub.3 O or CH.sub.3 CO; Y is S, SO, or SO.sub.2 ; Z is imidazol-1-yl, 2-methyl-imidazol-1-yl, pyrazol-1-yl or benzimidazol-1-yl; and n is 1, 2 or 3; or the physiologically acceptable acid addition salts thereof; are useful as antihypertensive agents, for example.

Phenothiazine derivatives and a process for their preparation

2-Guanidinomethyl-indolines of the formula ##STR1## wherein R.sup.1 and R.sup.2 each independently is H or alkyl of 1-6 carbon atoms, and the physiologically acceptable acid addition salts thereof have good antihypertensive properties.

2-Guanidinomethyl-indolines

New phenoxy-amino-propanols of formula ##STR1## wherein R.sup.1 is alkenyl, alkynyl, alkoxyalkyl or alkenyloxyalkyl with 2-6 C atoms in each case or cycloalkyl with 3-8 C atoms; and R.sup.2 is alkyl or hydroxyalkyl with 1-6 C atoms in each case, cycloalkyl with 3-8 C atoms, aralkyl or aralkyl wherein the aryl radical is mono- to tri-substituted by alkyl, alkoxy, OH, F and/or Cl or mono-substituted by methylenedioxy, with a total of 7-15 C atoms in each case, and the physiologically acceptable acid addition salts thereof, exhibit various pharmacological properties including isoprenaline-antagonism on the heart rate and blood pressure.

Phenoxy-amino-propanols

Adenine derivatives of the formula ##SPC1## Wherein R is phenyl or thienyl, and the physiologically acceptable acid addition salts thereof, possess, with good compatibility, cardio-active properties and are produced by the reaction of a purine derivative of the formula ##SPC2## Wherein X is F, Cl, Br, I, SR.sub.1, SOR.sub.1, SO.sub.2 R.sub.1 or OSi(CH.sub.3).sub.3, R.sub.1 being alkyl of 1-4 carbon atoms, phenyl or benzyl, with an amine of the formula ##SPC3## Wherein R has the values given above, or a salt thereof.

Pharmaceutical compositions containing adenine derivatives

Novel isoquinoline derivatives of the formula ##SPC1## Wherein R.sub.1 is H or, together with R.sub.2, a C--N bond; R.sub.2 is H, R.sub.8 or, together with R.sub.1, a C--N bond; R.sub.3 is H, methyl or ethyl; R.sub.4 and R.sub.5 each are H or collectively a C--C bond; and R.sub.6 and R.sub.7 each are H or methoxy; R.sub.8 being acyl of 1-10 carbon atoms or alkyl of 1-17 carbon atoms optionally mono- or polysubstituted by phenyl, OH, ArCOO--, ArCONH--, piperidino, 3,4-dehydropiperidino, morpholino, carboxy, carbomethoxy and/or carbethoxy, Ar being 3,4,5-trimethoxyphenyl; and the physiologically acceptable acid addition salts and quaternary ammonium salts thereof, have cardiovascular activity and can be prepared by acylating a corresponding primary amine lacking the COAr group with 3,4,5-trimethoxybenzoic acid or a functional derivative thereof.

Growing community of inventors

Traisa, Germany

Hans-Jochen Schliep