NITRATE ESTERS OF PIPERIDINES

1 . A compound of the general formula (I)

wherein

R 1 is aryl or heterocyclyl, in particular benzimidazolyl, benzo[1,3]dioxolyl, benzofuranyl, benzooxazolyl, benzothiazolyl, benzo[b]thienyl, quinazolinyl, quinolyl, quinoxalinyl, 2H-chromenyl, 3,4-dihydro-2H-benzo[1, 4]oxazinyl, dihydro-3H-benzo-[1,4]oxazinyl, dihydro-2H-benzo[1,4]thiazinyl, 1a,7b-dihydro-1H-cyclopropa[c]chromenyl, 2,3-dihydro-1H-indolyl, dihydro-1H-pyrido[2,3-b][1,4]oxazinyl, imidazo[1,2-a]pyridyl, imidazo[1,5-a]pyridyl, indazolyl, indolyl, isobenzofuranyl, isoquinolyl, [1,5]naphthyridyl, phenyl, phthalazinyl, pyridyl, pyrimidinyl, 1H-pyrrolo[2,3-b]pyridyl, 1H-pyrrolo[2,3-c]pyridyl, 1H-pyrrolo[3,2-b]pyridyl, tetrahydro-quinolyl, tetrahydroquinoxalinyl, 1,1a,2,7b-tetrahydro-cyclopropa[c]chromenyl, tetrahydroimidazo[1,2-a]-pyridyl, tetrahydroimidazo[1,5-a]pyridyl, tetrahydro-isoquinolyl[1,2,3]triazolo[1,5-a]pyridyl or [1,2,4] triazolo[4,3-a]pyridyl, which are substituted by 1-4 acyl-C 1-8 -alkoxy-C 1-8 -alkoxy, acyl-C 1-8 -alkoxy-C 1-8 -alkyl, (N-acyl)-C 1-8 -alkoxy-C 1-8 -alkylamino, C 1-8 -alkanoyl, C 1-8 -alkoxy, C 1-8 -alkoxy-C 1-8 -alkanoyl, C 1-8 -alkoxy-C 1-8 -alkoxy, C 1-8 -alkoxy-C 1-8 -alkoxy-C 1-8 -alkyl, C 1-8 -alkoxy-C 1-8 -alkyl, (N—C 1-8 -alkoxy)-C 1-8 -alkylamino-carbonyl-C 1-8 -alkoxy, (N—C 1-8 -alkoxy)-C 1-8 -alkylamino-carbonyl-C 1-8 -alkyl, C 1-8 -alkoxy-C 1-8 -alkylcarbamoyl, C 1-8 -alkoxy-C 1-8 -alkylcarbonyl, C 1-8 -alkoxy-C 1-8 -alkyl-carbonylamino, 1-C 1-8 -alkoxy-C 1-8 -alkylheterocyclyl, C 1-8 -alkoxyaminocarbonyl-C 1-8 -alkoxy, C 1-8 -alkoxyamino-carbonyl-C 1-8 -alkyl, C 1-8 -alkoxycarbonyl, C 1-8 -alkoxy-carbonyl-C 1-8 -alkoxy, C 1-8 -alkoxycarbonyl-C 1-8 -alkyl, C 1-8 -alkoxycarbonylamino-C 1-8 -alkoxy, C 1-8 -alkoxycarbonyl-amino-C 1-8 -alkyl, C 1-8 -alkyl, (N—C 1-8 -alkyl)-C 1-8 -alkoxy-C 1-8 -alkylcarbamoyl, (N—C 1-8 -alkyl)-C 1-8 -alkoxy-C 1-8 -alkyl-carbonylamino, (N—C 1-8 -alkyl)-C 1-8 -alkoxycarbonylamino, (N—C 1-8 -alkyl)-C 1-8 -alkylcarbonylamino-C 1-8 -alkoxy, (N—C 1-8 -alkyl-C 1-8 -alkylcarbonylamino-C 1-8 -alkyl, (N—C 1-8 -alkyl)-C 1-8 -alkylsulphonylamino-C 1-8 -alkoxy, (N—C 1-8 -alkyl)-C 1-8 -alkylsulphonylamino-C 1-8 -alkyl, C 1-8 -alkylamidinyl, C 1-8 -alkylamino-C 1-8 -alkoxy, di-C 1-8 -alkylamino-C 1-8 -alkoxy, C 1-8 -alkylamino-C 1-8 -alkyl, di-C 1-8 -alkylamino-C 1-8 -alkyl, C 1-8 -alkylaminocarbonyl-C 1-8 -alkoxy, di-C 1-8 -alkylamino-carbonyl-C 1-8 -alkoxy, C 1-8 -alkylaminocarbonyl-C 1-8 -alkoxy-C 1-8 -alkyl, C 1-8 -alkylaminocarbonyl-C 1-8 -alkyl, di-C 1-8 -alkyl-aminocarbonyl-C 1-8 -alkyl, C 1-8 -alkylamino-carbonylamino-C 1-8 -alkoxy, C 1-8 -alkyl-aminocarbonylamino-C 1-8 -alkyl, C 1-8 -alkylcarbonylamino, C 1-8 -alkylcarbonyl-amino-C 1-8 -alkoxy, C 1-8 -alkylcarbonylamino-C 1-8 -alkyl, C 1-8 -alkylcarbonyloxy-C 1-8 -alkoxy, C 1-8 -alkylcarbonyloxy-C 1-8 -alkyl, C 1-8 -alkylsulphonyl, C 1-8 -alkylsulphonyl-C 1-8 -alkoxy, C 1-8 -alkylsulphonyl-C 1-8 -alkyl, C 1-8 -alkyl-sulphonylamino-C 1-8 -alkoxy, C 1-8 -alkylsulphonylamino-C 1-8 -alkyl, unalkylated N-mono- or N,N-di-C 1-8 -alkylated amino, aryl-C 0-8 -alkoxy, aryl-C 0-8 -alkyl, unalkylated or N-mono- or N,N-di-C 1-8 -alkylated carbamoyl-C 0-8 -alkoxy, unalkylated or N-mono- or N,N-di-C 1-8 -alkylated carbamoyl-C 0-8 -alkyl, carboxy-C 1-8 -alkoxy, carboxy-C 1-8 -alkoxy-C 1-8 -alkyl, carboxy-C 1-8 -alkyl, cyano, cyano-C 1-8 -alkoxy, cyano-C 1-8 -alkyl, C 3-8 -cycloalkyl-C 1-8 -alkoxy, C 3-8 -cycloalkyl-C 1-8 -alkyl, C 3-8 -cycloalkylcarbonylamino-C 1-8 -alkoxy, C 3-8 -cycloalkylcarbonylamino-C 1-8 -alkyl, O,N-dimethylhydroxyamino-C 1-8 -alkyl, halogen, halogeno-C 1-8 -alkoxy, halogeno-C 1-8 -alkyl, heterocyclyl-C 0-8 -alkoxy, heterocyclyl-C 0-8 -alkyl, heterocyclylcarbonyl, hydroxy-C 1-8 -alkoxy-C 1-8 -alkoxy, hydroxy-C 1-8 -alkoxy-C 1-8 -alkyl, hydroxy-C 1-8 -alkyl, O-methyloximyl-C 1-8 -alkyl, oxide or oxo;

R 2 is C 2-8 -alkenyloxy-C 1-8 -alkoxy, C 2-8 -alkenyloxy-C 1-8 -alkyl, C 1-8 -alkoxy, C 1-8 -alkoxy-C 1-8 -alkoxy, unsubstituted or halogen-substituted C 1-8 -alkoxy-C 1-8 -alkoxy-C 1-8 -alkyl, C 1-8 -alkoxy-C 1-8 -alkyl, C 1-8 -alkoxy-C 1-8 -alkylamino-C 1-8 -alkoxy, C 1-8 -alkoxy-C 1-8 -alkylamino-C 1-8 -alkyl, C 1-8 -alkoxy-C 1-8 -alkylsulphanyl-C 1-8 -alkoxy, C 1-8 -alkoxy-C 1-8 -alkylsulphanyl-C 1-8 -alkyl, C 1-8 -alkoxy-C 0-8 -alkyl-C 3-8 -cycloalkyl-C 0-8 -alkoxy-C 1-8 -alkyl, C 1-8 -alkyl, C 1-8 -alkyl-sulphanyl-C 1-8 -alkoxy, C 1-8 -alkylsulphanyl-C 1-8 -alkoxy-C 1-8 -alkoxy, C 1-8 -alkylsulphanyl-C 1-8 -alkoxy-C 1-8 -alkyl, C 1-8 -alkylsulphanyl-C 1-8 -alkyl, C 1-8 -alkylsulphonyl-C 1-8 -alkoxy-C 1-8 -alkoxy, C 1-8 -alkylsulphonyl-C 1-8 -alkoxy-C 1-8 -alkyl, aryl-C 0-8 -alkoxy-C 1-8 -alkoxy, aryl-C 1-8 -alkoxy-C 1-8 -alkyl, aryloxy, C 3-8 -cycloalkyl-C 0-8 -alkoxy-C 1-8 -alkoxy, C 3-8 -cycloalkyl-C 0-8 -alkoxy-C 1-8 -alkoxy-C 1-8 -alkyl, C 3-8 -cycloalkyl-C 0-8 -alkoxy-C 1-8 -alkyl, heterocyclyl-C 0-8 -alkoxy-C 1-8 -alkoxy, heterocyclyl-C 0-8 -alkoxy-C 1-8 -alkyl or heterocyclyloxy;

R 3 is halogen,

R 4 is acyl, C 2-8 -alkenyl, C 1-8 -alkyl, aryl-C 1-8 -alkyl or hydrogen;

X is -Alk-, —O-Alk-, -Alk-O—, —O-Alk-O—, —S-Alk-, -Alk-S—, -Alk-NR 4 —, —NR 4 -Alk-, —C(O)—NR 4 —, -Alk-C(O)—NR 4 —, —O-Alk-C(O)—NR 4 —, —C(O)—NR 4 -Alk-, -Alk-C(O)—NR 4 -Alk-, —NR 4 —C(O)—, -Alk-NR 4 —C(O)—, —NR 4 —C(O)-Alk-, -Alk-NR 4 —C(O)-Alk-, —O-Alk-C(O)—NR 4 —, —O-Alk-NR 4 —C(O)—, —S(O) 2 —NR 4 —, -Alk-S(O) 2 —NR 4 —, —S(O) 2 —NR 4 -Alk-, -Alk-S(O) 2 —NR 4 -Alk-, —NR 4 —S(O) 2 —, -Alk-NR 4 —S(O) 2 —, —NR 4 —S(O) 2 -Alk- or -Alk-NR 4 —S(O) 2 -Alk-, where Alk designates C 1-8 -alkylene which is unsubstituted or substituted by halogen;

Y is a) unsubstituted or heterocyclyl- and/or halogen- and/or hydroxy- and/or C 1-8 -alkoxy-substituted

-Alk-,

-Alk-O-Alk-,

-Alk-NR 4 -Alk-,

-Alk-C(O)-Alk-,

-Alk-C(O)—NR 4 -Alk-,

-Alk-C(O)-Alk-NR 4 -Alk-,

-Alk-NR 4 —C(O)-Alk- or

-Alk-NR 4 -Alk-C(O)-Alk-,

where Alk designates linear or branched C 1-8 -alkylene; or

b) if p=0, is additionally

i) a bond

ii) unsubstituted or heterocyclyl- and/or halogen- and/or hydroxy- and/or C 1-8 -alkoxy-substituted

-Alk-O—,

-Alk-NR 4 —,

-Alk-C(O)— or

-Alk-NR 4 —C(O)-Alk-O—,

where Alk designates linear or branched C 1-8 -alkylene;

Z 0 is equal to —U-Z 1 -

wherein Z, is —C(O)—O—, —O—C(O)O—, —C(O)—NR 7 —C(O) or —O—C(O)—NR 7 —C(O)—, wherein

R 7 is as defined below;

U is a bivalent radical having the following meaning:

a)

C 1-8 -alkylene, unsubstituted or substituted with one or more of the substituents selected from the group consisting of: halogen, hydroxy, —ONO 2 or T o , wherein T o is —OC(O)—(C 1-8 -alkyl)-ONO 2 or —O—(C 1-8 -alkyl)-ONO 2 ;

C 3-8 -cycloalkylene, the ring being unsubstituted or substituted with side chains T, wherein T is C 1-8 -alkyl;

b)

wherein v is an integer from 0 to 20, and v1 is an integer from 1 to 20;

c)

wherein v is an integer from 0 to 20, and v1 is an integer from 1 to 20;

d)

wherein:

v1 is as defined above and v2 is an integer from 0 to 2;

Z 2 =—O—C(O)— or —C(O)—O— and R 5 is H or CH 3 ;

e)

wherein:

v1, v2, R 5 and Z 2 are as defined above;

U 1 is —CH 2 —CH 2 — or —CH═CH—(CH 2 ) v2 —;

f)

wherein:

v1 and R 5 are as defined above, R 6 is H or —C(O)CH 3 ;

g)

wherein Z 3 is —O—, or —S—, v3 is an integer from 1 to 6, R 5 is as defined above; or

h)

wherein:

v4 is an integer from 0 to 10;

v5 is an integer from 1 to 10;

R 7 , R 8 , R 9 , R 10 are the same or different, and are H or C 1-4 alkyl;

U 2 is a heterocyclic saturated, unsaturated or aromatic 5 or 6 membered ring, containing one or more heteroatoms selected from nitrogen, oxygen and sulphur, and is preferably selected from

m is 0, 1 or 2;

n is 0 or 1;

p is 0 or 1;

q is 0 or 1;

where, if p is =0, q is =1, and if p is =1, q is =0,

and their salts, preferably their pharmaceutically usable salts.

2 . A compound according to claim 1 , whereby said compound has the general formula

wherein R 1 , R 2 , R 3 , X, Y and Z 0 , and m, n, p and q have the meaning indicated for the compounds of the formula (I) in claim 1 .

3 . A compound according to claim 1 , characterized in that R 1 is benzimidazolyl, 2H-chromenyl, 3,4-dihydro-2H-benzo[1,4]oxazinyl, 1a,7b-dihydro-1H-cyclopropa[c]-chromenyl, indazolyl, indolyl, 2,3-dihydro-1H-indolyl, phenyl or 1,1a,2,7b-tetrahydrocyclopropa[c]chromenyl, which are mono- or polysubstituted by C 1-8 -alkoxy, C 1-8 -alkoxy-C 1-8 -alkoxy, C 1-8 -alkoxy-C 1-8 -alkoxy-C 1-8 -alkyl, C 1-8 -alkoxy-C 1-8 -alkyl, C 1-8 alkoxycarbonylamino-C 1-8 -alkoxy, C 1-8 -alkoxy-carbonylamino-C 1-8 -alkyl, C 1-8 -alkyl, (N—C 1-8 -alkyl)-C 1-8 -alkylcarbonylamino-C 1-8 -alkoxy, (N—C 1-8 -alkyl)-C 1-8 -alkylcarbonylamino-C 1-8 -alkyl, (N—C 1-8 -alkyl)-C 1-8 -alkylsulphonylamino-C 1-8 -alkoxy, (N—C 1-8 -alkyl)-C 1-8 -alkylsulphonylamino-C 1-8 -alkyl, C 1-8 -alkylcarbonylamino-C 1-8 -alkoxy, C 1-8 -alkyl-carbonylamino-C 1-8 -alkyl, C 1-8 alkylsulphonyl-C 1-8 -alkoxy, C 1-8 -alkyl-sulphonyl-C 1-8 -alkyl, C 1-8 -alkylsulphonylamino-C 1-8 alkoxy, C 1-8 -alkylsulphonylamino-C 1-8 -alkyl, C 3-8 -cycloalkylcarbonylamino-C 1-8 -alkoxy, C 3-8 -cycloalkyl-carbonylamino-C 1-8 -alkyl, halogen, halo-C 1-8 -alkoxy, halo-C 1-8 -alkyl or oxide.

4 . A compound according to claim 1 , whereby m is =0.

5 - 7 . (canceled)

8 . A method for the prevention, delay of the development or of the treatment of disease states which are caused, partly caused by or associated with the renin activity and a nitrogen monoxide deficiency or whose state can be improved by inhibition of the renin system and by supply of nitrogen monoxide, in which a therapeutically efficacious amount of a compound according to claim 1 can be used.

9 . A pharmaceutical preparation comprising a compound according to claim 1 and a common additive.

10 . A pharmaceutical combination in the form of a preparation or of a kit of individual components consisting of a) a compound according to claim 1 and b) at least one pharmaceutical form whose active agent has a blood pressure-lowering, inotropic, anti-diabetic, lipid-lowering or anti-oxidative effect.

11 . A method for the prevention, delay of the development or of the treatment of disease states which are caused, partly caused by or associated with the renin activity and a nitrogen monoxide deficiency or whose state can be improved by inhibition of the renin system and by supply of nitrogen monoxide, in which a therapeutically efficacious amount of a compound according to claim 2 can be used.

12 . A pharmaceutical preparation comprising a compound according to claim 2 and a common additive.

13 . A pharmaceutical combination in the form of a preparation or of a kit of individual components consisting of a) a compound according to claim 2 and b) at least one pharmaceutical form whose active agent has a blood pressure-lowering, inotropic, anti-diabetic, lipid-lowering or anti-oxidative effect.

14 . A compound according to claim 2 , characterized in that

R 1 is benzimidazolyl, 2H-chromenyl, 3,4-dihydro-2H-benzo[1,4]oxazinyl, 1a,7b-dihydro-1H-cyclopropa[c]-chromenyl, indazolyl, indolyl, 2,3-dihydro-1H-indolyl, phenyl or 1,1a,2,7b-tetrahydrocyclopropa[c]chromenyl, which are mono- or polysubstituted by C 1-8 -alkoxy, C 1-8 -alkoxy-C 1-8 -alkoxy, C 1-8 -alkoxy-C 1-8 -alkoxy-C 1-8 -alkyl, C 1-18 -alkoxy-C 1-8 -alkyl, C 1-8 -alkoxycarbonylamino-C 1-8 -alkoxy, C 1-8 -alkoxy-carbonylamino-C 1-8 -alkyl, C 1-8 -alkyl, (N—C 1-8 -alkyl)-C 1-8 -alkylcarbonylamino-C 1-8 -alkoxy, (N—C 1-8 -alkyl)-C 1-8 -alkylcarbonylamino-C 1-8 -alkyl, (N—C 1-8 -alkyl)-C 1-8 -alkylsulphonylamino-C 1-8 -alkoxy, (N—C 1-8 -alkyl)-C 1-8 -alkylsulphonylamino-C 1-8 -alkyl, C 1-8 -alkylcarbonylamino-C 1-8 -alkoxy, C 1-8 -alkyl-carbonylamino-C 1-8 -alkyl, C 1-8 -alkylsulphonyl-C 1-8 -alkoxy, C 1-8 -alkyl-sulphonyl-C 1-8 -alkyl, C 1-8 -alkylsulphonylamino-C 1-8 -alkoxy, C 1-8 -alkylsulphonylamino-C 1-8 -alkyl, C 3-8 -cycloalkylcarbonylamino-C 1-8 -alkoxy, C 3-8 -cycloalkyl-carbonylamino-C 1-8 -alkyl, halogen, halo-C 1-8 -alkoxy, halo-C 1-8 -alkyl or oxide.

15 . A compound according to claim 2 , characterized in that m is =0.