Bicyclically substituted uracils and the use thereof

1. A method for treatment and/or prophylaxis of a cardiovascular disorder comprising administering an effective amount of a compound of the formula (I)

wherein

R 1 is hydrogen or (C 1 -C 4 )-alkyl,

R 2 is a group of the formula

wherein

* is the attachment site to the uracil nitrogen atom,

A is —CH 2 —, —CH 2 —CH 2 —, —O—CH 2 -## or oxygen,

wherein

## is the attachment site to the phenyl ring,

m is a number 0, 1 or 2,

R 4 is halogen, difluoromethyl, trifluoromethyl, (C 1 -C 4 )-alkyl, difluoromethoxy, trifluoromethoxy or (C 1 -C 4 )-alkoxy,

R 5A is hydrogen or deuterium,

R 5B is hydrogen, deuterium or (C 1 -C 4 )-alkyl,

R 6 is hydrogen or fluorine,

R 7 is hydrogen or fluorine,

R 8 is halogen, difluoromethyl, trifluoromethyl, (C 1 -C 4 )-alkyl or nitro,

R 9 is hydrogen, halogen, difluoromethyl, trifluoromethyl, (C 1 -C 4 )-alkyl, nitro or (C 1 -C 4 )-alkylthio,

R 3 is a group of the formula

wherein

# is the attachment site to the uracil nitrogen atom,

the ring Q is 5- to 7-membered heterocyclyl or 5- or 6-membered heteroaryl,

wherein 5- to 7-membered heterocyclyl and 5- or 6-membered heteroaryl may be substituted by 1 to 4 substituents independently selected from the group consisting of halogen, difluoromethyl, trifluoromethyl, trideuteromethyl, (C 1 -C 6 )-alkyl, (C 3 -C 7 )-cycloalkyl, oxo, hydroxyl, (C 1 -C 4 )-alkylcarbonyl, (C 1 -C 4 )-alkoxycarbonyl, aminocarbonyl and (C 1 -C 4 )-alkylsulphonyl,

wherein (C 1 -C 6 )-alkyl and (C 3 -C 7 )-cycloalkyl may in turn be substituted by 1 to 3 substituents independently selected from the group consisting of halogen, cyano, trifluoromethyl, (C 3 -C 7 )-cycloalkyl, hydroxyl, (C 1 -C 4 )-alkoxy and 4- to 7-membered heterocyclyl,

 and

wherein two (C 1 -C 6 )-alkyl radicals bonded to a carbon atom of 5- to 7-membered heterocyclyl and 5- or 6-membered heteroaryl, together with the carbon atom to which they are bonded, may form a 3- to 6-membered carbocycle,

R 24 is halogen, (C 1 -C 4 )-alkyl or (C 1 -C 4 )-alkoxy, and

n is a number 0, 1, 2 or 3,

or a salt, a solvate, or a solvate of a salt thereof, and wherein the cardiovascular disorder is selected from the group consisting of atherosclerosis, peripheral vascular disorder, cardiac vascular disorder, micro- and macrovascular damage, vasculitis, restenosis, and endothelial dysfunction.

2. The method according to claim 1 , wherein

R 1 is hydrogen, methyl or ethyl,

R 2 is a group of the formula

wherein

* is the attachment site to the uracil nitrogen atom,

A is —CH 2 —, —CH 2 —CH 2 —, —O—CH 2 -## or oxygen,

wherein

## is the attachment site to the phenyl ring,

R 4A is hydrogen, fluorine, chlorine, trifluoromethyl or methyl,

R 4B is hydrogen, fluorine, chlorine, trifluoromethyl or methyl,

with the proviso that at least one of the R 4A and R 4B radicals is not hydrogen,

R 5A is hydrogen,

R 5B is hydrogen,

R 6 is hydrogen,

R 7 is hydrogen,

R 8 is fluorine, chlorine, difluoromethyl, trifluoromethyl or methyl,

R 9 is fluorine, chlorine, difluoromethyl, trifluoromethyl or methyl,

R 3 is a group of the formula

wherein

# is the attachment site to the uracil nitrogen atom,

E 1 is CR 11 or N,

wherein

R 11 is hydrogen, (C 1 -C 4 )-alkyl, (C 3 -C 7 )-cycloalkyl or aminocarbonyl,

E 2 is CR 12 or N,

wherein

R 12 is hydrogen, (C 1 -C 4 )-alkyl or (C 3 -C 7 )-cycloalkyl,

E 3 is NR 14 or S,

wherein

R 14 is hydrogen, (C 1 -C 4 )-alkyl or (C 3 -C 7 )-cycloalkyl,

G 1 is C═O or SO 2 ,

G 2 is CR 16A R 16B , NR 17 , O or S,

wherein

R 16A is hydrogen, fluorine, (C 1 -C 4 )-alkyl or hydroxyl,

R 16B is hydrogen, fluorine, chlorine, (C 1 -C 4 )-alkyl or trifluoromethyl,

or

R 16A and R 16B together with the carbon atom to which they are bonded form a 3- to 6-membered carbocycle,

R 17 is hydrogen, (C 1 -C 6 )-alkyl, (C 3 -C 7 )-cycloalkyl or (C 1 -C 4 )-alkoxycarbonyl, wherein (C 1 -C 6 )-alkyl may be substituted by 1 to 3 substituents independently selected from the group consisting of fluorine, trifluoromethyl, cyano, (C 3 -C 7 )-cycloalkyl, hydroxyl, trifluoromethoxy, (C 1 -C 4 )-alkoxy, azetidinyl, oxetanyl, tetrahydrofuranyl and pyrrolidinyl,

G 3 is CR 18A R 18B , NR 19 , O or S,

wherein

R 18A is hydrogen, fluorine, (C 1 -C 4 )-alkyl or hydroxyl,

R 18B is hydrogen, fluorine, chlorine, (C 1 -C 4 )-alkyl or trifluoromethyl,

or

R 18A and R 18B together with the carbon atom to which they are bonded form a 3- to 6-membered carbocycle,

R 19 is hydrogen, (C 1 -C 6 )-alkyl, (C 3 -C 7 )-cycloalkyl or (C 1 -C 4 )-alkoxycarbonyl, wherein (C 1 -C 6 )-alkyl may be substituted by 1 to 3 substituents independently selected from the group consisting of fluorine, trifluoromethyl, cyano, (C 3 -C 7 )-cycloalkyl, hydroxyl, trifluoromethoxy, (C 1 -C 4 )-alkoxy, azetidinyl, oxetanyl, tetrahydrofuranyl and pyrrolidinyl,

G 4 is —CH 2 , C═O or SO 2 ,

K 1 is —CH 2 or O,

K 2 is —CH 2 or O,

with the proviso that only one of the K 1 and K 2 groups is O,

D 1 , D 2 , D 3 and D 4 are each independently CR 23 or N,

wherein

R 23 is hydrogen, halogen, (C 1 -C 6 )-alkyl or (C 3 -C 7 )-cycloalkyl,

with the proviso that not more than 2 of the D 1 , D 2 , D 3 and D 4 groups are N,

R 24 is fluorine or methyl,

n is a number 0 or 1,

R 10 is (C 1 -C 4 )-alkyl or (C 3 -C 7 )-cycloalkyl,

wherein (C 1 -C 4 )-alkyl may be substituted by 1 or 2 substituents independently selected from the group consisting of fluorine, trifluoromethyl, cyclopropyl, cyclobutyl, hydroxyl, methoxy, ethoxy, azetidinyl, oxetanyl, tetrahydrofuranyl and pyrrolidinyl,

R 13 is hydrogen, (C 1 -C 4 )-alkyl or (C 3 -C 7 )-cycloalkyl,

R 15 is hydrogen, (C 1 -C 6 )-alkyl or (C 3 -C 7 )-cycloalkyl,

wherein (C 1 -C 6 )-alkyl may be substituted by 1 or 2 substituents independently selected from the group consisting of fluorine, trifluoromethyl, cyclopropyl, cyclobutyl, hydroxyl, methoxy, ethoxy, azetidinyl, oxetanyl, tetrahydrofuranyl and pyrrolidinyl,

R 20 is hydrogen, (C 1 -C 6 )-alkyl, (C 3 -C 7 )-cycloalkyl or (C 1 -C 4 )-alkylcarbonyl,

wherein (C 1 -C 6 )-alkyl may be substituted by 1 or 2 substituents independently selected from the group consisting of fluorine, trifluoromethyl, cyclopropyl, cyclobutyl, hydroxyl, methoxy, ethoxy, azetidinyl, oxetanyl, tetrahydrofuranyl and pyrrolidinyl,

R 21 is hydrogen, (C 1 -C 6 )-alkyl, (C 3 -C 7 )-cycloalkyl or (C 1 -C 4 )-alkylsulphonyl,

R 22A is hydrogen or (C 1 -C 4 )-alkyl,

R 22B is hydrogen or (C 1 -C 4 )-alkyl,

or

R 22A and R 22B together with the carbon atom to which they are bonded form a carbonyl group,

or a salt, a solvate, or a solvate of a salt thereof.

3. The method according to claim 1 , wherein

R 1 is hydrogen,

R 2 is a group of the formula

wherein

* is the attachment site to the uracil nitrogen atom,

A is —CH 2 —,

R 4A is chlorine or trifluoromethyl,

R 4B is hydrogen,

R 3 is a group of the formula

wherein

# is the attachment site to the uracil nitrogen atom,

E 1 is CR 11

wherein

R 11 is hydrogen,

E 2 is N,

G 1 is C═O,

G 2 is CR 16A R 16B , NR 17 , O or S,

wherein

R 16A is hydrogen, fluorine, methyl or hydroxyl,

R 16B is hydrogen, fluorine, methyl or trifluoromethyl,

or

R 16A and R 16B together with the carbon atom to which they are bonded form a cyclopropyl ring,

R 17 is hydrogen, (C 1 -C 4 )-alkyl or (C 3 -C 5 )-cycloalkyl,

wherein (C 1 -C 4 )-alkyl may be substituted by 1 to 3 substituents independently selected from the group consisting of fluorine, trifluoromethyl, cyano, cyclopropyl, cyclobutyl, hydroxyl, trifluoromethoxy, methoxy, ethoxy, azetidinyl, oxetanyl, tetrahydrofuranyl and pyrrolidinyl,

R 24 is hydrogen or fluorine,

R 10 is (C 1 -C 4 )-alkyl, and

R 15 is hydrogen, methyl or ethyl,

wherein methyl and ethyl may be substituted by 1 substituent selected from the group consisting of fluorine, trifluoromethyl and cyclopropyl,

or a salt, a solvate, or a solvate of a salt thereof.

4. The method according to claim 1 , wherein

R 1 is hydrogen,

R 2 is a group of the formula

wherein

* is the attachment site to the uracil nitrogen atom,

R 5A is hydrogen,

R 5B is hydrogen,

R 6 is hydrogen,

R 7 is hydrogen,

R 8 is fluorine, chlorine or trifluoromethyl,

R 9 is fluorine, chlorine, trifluoromethyl or methyl,

R 3 is a group of the formula

wherein

# is the attachment site to the uracil nitrogen atom,

E 1 is CR 11

wherein

R 11 is hydrogen,

E 2 is N,

G 1 is C═O,

G 2 is CR 16A R 16B , NR 17 , O or S,

wherein

R 16A is hydrogen, fluorine, methyl or hydroxyl,

R 16B is hydrogen, fluorine, methyl or trifluoromethyl,

or

R 16A and R 16B together with the carbon atom to which they are bonded form a cyclopropyl ring,

R 17 is hydrogen, (C 1 -C 4 )-alkyl or (C 3 -C 5 )-cycloalkyl,

wherein (C 1 -C 4 )-alkyl may be substituted by 1 to 3 substituents independently selected from the group consisting of fluorine, trifluoromethyl, cyano, cyclopropyl, cyclobutyl, hydroxyl, trifluoromethoxy, methoxy, ethoxy, azetidinyl, oxetanyl, tetrahydrofuranyl and pyrrolidinyl,

R 24 is hydrogen or fluorine,

R 10 is (C 1 -C 4 )-alkyl, and

R 15 is hydrogen, methyl or ethyl,

wherein methyl and ethyl may be substituted by 1 substituent selected from the group consisting of fluorine, trifluoromethyl and cyclopropyl,

or a salt, a solvate, or a solvate of a salt thereof.

5. The method according to claim 1 , wherein the compound is 1-(1,3-dimethyl-2-oxo-2,3-dihydro-1H-benzimidazol-5-yl)-2,4-dioxo-3-[(1R)-4-(trifluoromethyl)-2,3-dihydro-1H-inden-1-yl]-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid (R enantiomer) of the formula

or a salt, a solvate, or a solvate of a salt thereof.

6. The method according to claim 1 , wherein the compound is is 1-(6-fluoro-1,3-dimethyl-2-oxo-2,3-dihydro-1H-benzimidazol-5-yl)-2,4-dioxo-3-[(1R)-4-(trifluoromethyl)-2,3-dihydro-1H-inden-1-yl]-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid (R enantiomer) of the formula

or a salt, a solvate, or a solvate of a salt thereof.

7. The method according to claim 1 , wherein the compound is 1-(3-methyl-2-oxo-2,3-dihydro-1,3-benzoxazol-6-yl)-2,4-dioxo-3-[(1R)-4-(trifluoromethyl)-2,3-dihydro-1H-inden-1-yl]-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid (R enantiomer) of the formula

or a salt, a solvate, or a solvate of a salt thereof.

8. The method according to claim 1 , wherein the compound is 2,4-dioxo-3-[(1R)-4-(trifluoromethyl)-2,3-dihydro-1H-inden-1-yl]-1-(1,3,3-trimethyl-2-oxo-2,3-dihydro-1H-indol-5-yl)-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid (R enantiomer) of the formula

or a salt, a solvate, or a solvate of a salt thereof.

9. The method according to claim 1 , wherein the compound is 1-(1′-methyl-2′-oxo-1′,2′-dihydrospiro [cyclopropane-1,3′-indole]-5′-yl)-2,4-dioxo-3-[(1R)-4-(trifluoromethyl)-2,3-dihydro-1H-inden-1-yl]-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid (R enantiomer) of the formula

or a salt, a solvate, or a solvate of a salt thereof.

10. The method according to claim 1 , wherein the compound is 1-(3-methyl-2-oxo-2,3-dihydro-1,3-benzothiazol-6-yl)-2,4-dioxo-3-[(1R)-4-(trifluoromethyl)-2,3-dihydro-1H-inden-1-yl]-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid (R enantiomer) of the formula

or a salt, a solvate, or a solvate of a salt thereof.

11. The method according to claim 1 , wherein the compound is ethyl 1-(3-methyl-2-oxo-2,3-dihydro-1,3-benzoxazol-6-yl)-2,4-dioxo-3-[(1R)-4-(trifluoromethyl)-2,3-dihydro-1H-inden-1-yl]-1,2,3,4-tetrahydropyrimidine-5-carboxylate (R enantiomer) of the formula

or a salt, a solvate, or a solvate of a salt thereof.

12. The method of claim 1 , wherein the cardiovascular disorder is peripheral vascular disorder.

13. The method according to claim 1 , wherein the compound is 1-(1,3-dimethyl-2-oxo-2,3-dihydro-1H-benzimidazol-5-yl)-2,4-dioxo-3-[(1R)-4-(trifluoromethyl)-2,3-dihydro-1H-inden-1-yl]-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid (R enantiomer) of the formula

14. The method according to claim 1 , wherein the compound is 1-(6-fluoro-1,3-dimethyl-2-oxo-2,3-dihydro-1H-benzimidazol-5-yl)-2,4-dioxo-3-[(1R)-4-(trifluoromethyl)-2,3-dihydro-1H-inden-1-yl]-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid (R enantiomer) of the formula

15. The method according to claim 1 , wherein the compound is 1-(3-methyl-2-oxo-2,3-dihydro-1,3-benzoxazol-6-yl)-2,4-dioxo-3-[(1R)-4-(trifluoromethyl)-2,3-dihydro-1H-inden-1-yl]-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid (R enantiomer) of the formula

16. The method according to claim 1 , wherein the compound is 2,4-dioxo-3-[(1R)-4-(trifluoromethyl)-2,3-dihydro-1H-inden-1-yl]-1-(1,3,3-trimethyl-2-oxo-2,3-dihydro-1H-indol-5-yl)-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid (R enantiomer) of the formula

17. The method according to claim 1 , wherein the compound is 1-(1′-methyl-2′-oxo-1′,2′-dihydro spiro [cyclopropane-1,3′-indole]-5′-yl)-2,4-dioxo-3-[(1R)-4-(trifluoromethyl)-2,3-dihydro-1H-inden-1-yl]-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid (R enantiomer) of the formula

18. The method according to claim 1 , wherein the compound is 1-(3-methyl-2-oxo-2,3-dihydro-1,3-benzothiazol-6-yl)-2,4-dioxo-3-[(1R)-4-(trifluoromethyl)-2,3-dihydro-1H-inden-1-yl]-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid (R enantiomer) of the formula

19. The method according to claim 1 , wherein the compound is ethyl 1-(3-methyl-2-oxo-2,3-dihydro-1,3-benzoxazol-6-yl)-2,4-dioxo-3-[(1R)-4-(trifluoromethyl)-2,3-dihydro-1H-inden-1-yl]-1,2,3,4-tetrahydropyrimidine-5-carboxylate (R enantiomer) of the formula