Hoffmann-la Roche Inc.

Synthelabo

Jean-Claude Muller

Henri Ramuz

Christian Hoornaert

Urs O Hengartner

Gerard Cremer

Nigel R Beeley

Pascale Goberville

Pascal George

Jonathan Reid Frost

Thomas A Purcell

Daniel J Galtier

Icilio A Cavero

Lydia Zard

Peter Vogt

Andre Pierre Dumas

Corinne Rousselle

Patrick Pasau

Marquard Imfeld

Michel Aletru

Peter Hicks

Marc Daumas

Regine Bartsch

Francois Elkik

Howard Williams

Compounds which can be expressed as tautomeric forms and having the formulas (I), (I') and (I') ##STR1## wherein R.sub.1 =a straight or branched (C.sub.1-7) alkyl group or a straight or branched (C.sub.3-9) alkenyl group or a cyclo(C.sub.3-7)alkyl(C.sub.1-6) alkyl group, R.sub.2 =an atom of hydrogen, or a straight or branched (C.sub.1-7)alkyl group, or a cyclo(C.sub.3-7)alkyl(C.sub.1-3)alkyl group, or an aryl(C.sub.1-3)alkyl group optionally substituted on the ring, or an aryloxy(C.sub.1-3)alkyl group optionally substituted on the ring, or an arylthio(C.sub.1-3)alkyl group optionally substituted on the ring, or an arylsulfonyl(C.sub.1-3)alkyl group optionally substituted on the ring, or a heteroaryl(C.sub.1-3)alkyl group optionally substituted on the ring, R.sub.3 =CO.sub.2 H, 1H-tetrazol-5-yl, NHCOR.sub.11, NHSO.sub.2 R.sub.11, CONHSO.sub.2 R.sub.11 or CONHOR.sub.12 group where R.sub.11 =a methyl, trifluoromethyl, or phenyl group optionally substituted, R.sub.12 =a hydrogen atom, or a methyl or a phenyl group optionally substituted. The compounds are useful for antagonizing angiotensin II.

4-pyrimidinone derivatives their preparation and their application in

Compounds of the formula ##STR1## in which Y represents hydrogen, fluorine, chlorine, methyl or methoxy, R.sub.1 represents phenyl substituted by fluorine, methyl, methoxy, trifluoromethyl or phenyl, or R.sub.1 represents 2-thienyl, R.sub.2 represents methyl, and R.sub.3 represents (C.sub.1 -C.sub.4)-alkyl, or phenyl-(C.sub.1 -C.sub.2)-alkyl optionally substituted on the ring by 2 to 3 methoxy groups, or 2-(2-pyridyl)ethyl, or R.sub.2 and R.sub.3 form, with the adjacent nitrogen, 4-phenyl(1-piperidyl), 4-phenylmethyl(1-piperidyl), 1,2,3,4-tetrahydro-2-isoquinolyl, 6-methoxy-1,2,3,4-tetrahydro-2-isoquinolyl, 5,8-dimethoxy-1,2,3,4-tetrahydro-2-isoquinolyl, 6,7-dimethoxy 1,2,3,4-tetrahydro-2-isoquinolyl, 2,3,4,5-tetrahydro-1H-3-benzazepin-3-yl, or 7,8-dimethoxy-2,3,4,5-tetrahydro-1H-3-benzazepin-3-yl, and X represents carbonyl or sulphonyl, and their salts are useful as neuroprotective and antiiischaemic agents.

Benzoxazine derivatives and their application in therapy

The present invention provides a compound which is a quinoline derivative of the formula (I) ##STR1## in which R.sub.1 represents either 1H-tetrazol-5-yl, or CO.sub.2 H,

Quinoline derivatives

Quinoline derivatives, process for their preparation, and their

A compound of formula (I) ##STR1## in which: X denotes hydrogen, a halogen, a trifluoromethyl group, a C.sub.1 -C.sub.4 alkyl group or a C.sub.1 -C.sub.4 alkoxy group;

N-aminobutyl-n-phenylarylamide derivatives, their preparation and their

N-aminobutyl-n-phenylarylamide compounds and their application in therapy

Compositions of diltiazem and angiotensin-converting enzyme inhibitor useful for the treatment of hypertension, cardiac insufficiency and coronary insufficiency.

Pharmaceutical composition containing diltiazem and

Compounds which are 1,5-benzothiazepine derivatives of general formula (I) ##STR1## in which R denotes hydrogen or C.sub.1 -C.sub.4 alkyl and R.sub.1 and R.sub.2 either separately denote C.sub.1 -C.sub.4 alkyl groups or together denote a tetramethylene or pentamethylene group and their acid addition salts are therapeutically active as calcium antagonists.

1,5-benzothiazepine derivatives and compositions containing them

Novel pyrimidinedicarbamates of the formula ##STR1## wherein R is lower alkyl or (lower alkyloxy)-(lower alkyl) and X is a leaving group, can be manufactured by carbamoylating the corresponding free diamines. They are valuable intermediates and can be used, for example, for the manufacture of corresponding oxadiazolopyrimidines of the formula ##STR2## and pharmaceutically acceptable salts thereof. The latter have valuable long-lasting vasodilating and/or bloodpressure lowering properties and are accordingly suitable especially for the treatment of vascular-conditioned hypertensions or as vasodilators in the case of peripheral blood supply disorders.

Dicarbamates

2,4-Disubstituted 6-[3,6-dihydro-1(2H)-pyridyl]pyrimidine-3-oxides of the formula ##STR1## wherein R.sup.1 is lower alkyl or lower alkoxy-lower alkyl, R.sup.2 is hydrogen or --COOR.sup.3 wherein R.sup.3 is lower alkyl or lower alkoxy-lower alkyl, which are important for the preparation of therapeutically valuable 1,2,5,6-tetrahydropyridyl-substituted 2-oxo-2H-[1,2,4]oxadiazolopyrimidinecarbamates, are described. The foregoing oxides of formula I can be prepared by reacting the corresponding arylsulfonyloxy- or alkylsulfonyl-substituted derivatives with 1,2,5,6-tetrahydropyridine.

Pyrimidinecarbamate derivatives as intermediates

Oxadiazolo[2,3-c]pyrimidine derivatives of the formula ##STR1## wherein R is alkyl, alkenyl, alkynyl or alkoxyalkyl, as well as their salts, are described. The compounds of formula I have valuable, long-lasting vasodilating and/or blood pressure-lowering properties and are useful for the treatment of vascular-conditioned hypertensions or as vasodilators in peripheral blood supply disorders. The compounds are prepared, inter alia, by carbamoylating the corresponding derivative containing a free amino group and optional salt formation.

Oxadiazolopyrimidine derivatives

7[3,6-Dihydro-1(2H)-p

Oxadiazolotriazine derivatives of the formula ##STR1## wherein R.sup.1, R.sup.2 and R.sup.3 are as hereinafter set forth, are described. A process for preparing compounds of formula I wherein R.sup.1 is hydrogen, R.sup.2 is a group of the formula --COOR.sup.5, wherein R.sup.5 is as hereinafter set forth, and R.sup.3 is as hereinafter set forth, by cyclizing an intermediate of the formula ##STR2## wherein R.sup.3 and R.sup.5 are as hereinafter set forth, is also described. The compounds of formula I are useful in the treatment of vascular-condition hypertension or also as vasodilators in the case of peripheral blood supply disorders.

Oxadiazolotriazine derivatives

Oxadiazolotriazine derivatives of the formula ##STR1## wherein R.sup.1, R.sup.2 and R.sup.3 are as hereinafter set forth, are described. The compounds of formula I are useful in the treatment of vascular-condition hypertension or also as vasodilators in the case of peripheral blood supply disorders.

A process for preparing oxadiazolopyrimidines of the formula ##STR1## wherein R is alkyl or alkoxyalkyl, by reacting a compound of the formula ##STR2## wherein R is as set forth above, with phosgene, is described.

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Rixheim, France

Jean-Claude Muller