Substituted 3-phenylpropionic acids and the use thereof

1. A compound of the formula (I)

in which

R 1A represents hydrogen, fluorine, methyl, trifluoromethyl, ethyl, 1,1-difluoroethyl, 2,2,2-trifluoroethyl, n-propyl,

R 1B represents hydrogen or methyl,

R 2A represents hydrogen, methyl, trifluoromethyl, ethyl, 1,1-difluoroethyl, 2,2,2-trifluoroethyl or n-propyl, and

R 2B represents hydrogen or methyl,

R 3 represents hydrogen, fluorine, methyl or trifluoromethyl,

R 4 represents hydrogen, fluorine, chlorine, cyano, methyl, trifluoromethyl or ethyl,

R 5A represents methyl, trifluoromethyl or ethyl, and

R 5B represents trifluoromethyl,

or

R 5A and R 5B are attached to one another and together with the carbon atom to which they are attached form a difluoro-substituted cycloalkyl ring of the formula

R 6 represents hydrogen, fluorine, chlorine, bromine, cyano, (C 1 -C 4 )-alkyl, (C 2 -C 4 )-alkenyl, cyclopropyl or cyclobutyl, where

(C 1 -C 4 )-alkyl and (C 2 -C 4 )-alkenyl may be substituted up to three times by fluorine

and

cyclopropyl and cyclobutyl may be substituted up to two times by fluorine,

and

R 7 represents hydrogen, fluorine, chlorine, cyano, methyl, trifluoromethyl, ethyl, methoxy or trifluoromethoxy,

or a salt thereof.

2. The compound according to claim 1 in which

R 1A represents hydrogen, methyl, trifluoromethyl, ethyl, n-propyl,

R 1B represents hydrogen or methyl,

R 2A represents hydrogen, methyl, trifluoromethyl, ethyl or n-propyl,

R 2B represents hydrogen or methyl,

R 3 represents hydrogen, fluorine or methyl,

R 4 represents hydrogen, fluorine, chlorine, cyano, methyl or trifluoromethyl,

R 5A represents methyl or ethyl,

R 5B represents trifluoromethyl,

or

R 5A and R 5B are attached to one another and together with the carbon atom to which they are attached form a difluoro-substituted cycloalkyl ring of the formula

R 6 represents fluorine, chlorine, (C 1 -C 4 )-alkyl, (C 2 -C 3 )-alkenyl, cyclopropyl or cyclobutyl, where

(C 1 -C 4 )-alkyl and (C 2 -C 3 )-alkenyl may be substituted up to three times by fluorine

and

cyclopropyl and cyclobutyl may be substituted up to two times by fluorine,

and

R 7 represents hydrogen, fluorine, chlorine, methyl or methoxy,

or a salt thereof.

3. The compound according to claim 1 in which

R 1A represents hydrogen, methyl or ethyl,

R 1B represents hydrogen,

R 2A represents hydrogen, methyl, trifluoromethyl, ethyl or n-propyl,

R 2B represents hydrogen or methyl,

R 3 represents hydrogen,

R 4 represents fluorine, chlorine or methyl,

R 5A represents methyl,

R 5B represents trifluoromethyl,

or

R 5A and R 5B are attached to one another and together with the carbon atom to which they are attached form a difluoro-substituted cyclopentyl ring of the formula

R 6 represents fluorine, chlorine, methyl, trifluoromethyl, ethyl, 1,1-difluoroethyl, 2,2,2-trifluoroethyl, isopropyl, tert-butyl, 1,1,1-trifluoro-2-methylpropan-2-yl, vinyl, 1-fluorovinyl, cyclopropyl, 2,2-difluorocyclopropyl, cyclobutyl or 3,3-difluorocyclobutyl,

and

R 7 represents hydrogen, fluorine, chlorine or methyl,

or a salt thereof.

4. The compound according to claim 1 , wherein the compound is

(+)-3-(3-{[(2S,3R)-2-(4-tert-butylphenyl)-4,4,4-trifluoro-3-methylbutanoyl]amino}-4-chlorophenyl)propanoic acid;

3-[4-Chloro-3-({4,4,4-trifluoro-3-methyl-2-[4-(2,2,2-trifluoroethyl)phenyl]butanoyl}amino)phenyl]propanoic acid;

3-(4-chloro-3-{[(2S,3R)-2-(4-ethylphenyl)-4,4,4-trifluoro-3-methylbutanoyl]amino}phenyl)butanoic acid;

(3S)-3-(4-chloro-3-{[(4-chlorophenyl)(2,2-difluorocyclopentyl)acetyl]amino}phenyl)butanoic acid;

(+)-3-(4-Chloro-3-{[(2S,3R)-2-(4-chlorophenyl)-4,4,4-trifluoro-3-methylbutanoyl]amino}phenyl)propanoic acid;

(+)-(2S)-3-(4-Chloro-3-{[(2S,3R)-2-(4-chlorophenyl)-4,4,4-trifluoro-3-methylbutanoyl]amino}phenyl)-2-methylpropanoic acid;

(+)-(2S)-2-(4-Chloro-3-{[(2S,3R)-2-(4-chlorophenyl)-4,4,4-trifluoro-3-methylbutanoyl]amino}benzyl)butanoic acid;

3-(3-{[(3R)-2-(4-Chlorophenyl)-4,4,4-trifluoro-3-methylbutanoyl]amino}-4-fluorophenyl)-2-methylpropanoic acid;

threo-3-(3-{[(2S,3R)-2-(4-chlorophenyl)-4,4,4-trifluoro-3-methylbutanoyl]amino}-4-fluorophenyl)-2-methylbutanoic acid;

(+)-2-(4-Chloro-3-{[(2S,3R)-2-(4-chlorophenyl)-4,4,4-trifluoro-3-methylbutanoyl]amino}benzyl)-2-methylbutanoic acid;

3-(4-Chloro-3-{[(2S,3R)-2-(4-chlorophenyl)-4,4,4-trifluoro-3-methylbutanoyl]amino}phenyl)hexanoic acid;

(+)-3-(4-Chloro-3-{[(2S,3R)-2-(4-chlorophenyl)-4,4,4-trifluoro-3-methylbutanoyl]amino}phenyl)hexanoic acid;

(+)-3-(4-Chloro-3-{[(2S,3R)-2-(4-chlorophenyl)-4,4,4-trifluoro-3-methylbutanoyl]amino}phenyl)-4,4,4-trifluorobutanoic acid;

(+)-3-(4-Chloro-3-{[(2S,3R)-2-(4-chlorophenyl)-4,4,4-trifluoro-3-methylbutanoyl]amino}phenyl)pentanoic acid;

3-(4-chloro-3-{[(2S,3R)-2-(4-chlorophenyl)-4,4,4-trifluoro-3-methylbutanoyl]amino}phenyl)-2,2-dimethylpropanoic acid;

(2S)-3-[4-chloro-3-({4,4,4-trifluoro-3-methyl-2-[4-(2,2,2-trifluoroethyl)phenyl]butanoyl}amino)phenyl]-2-methylpropanoic acid;

(2S)-3-[4-chloro-3-({(2S,3R)-2-[4-(3,3-difluorocyclobutyl)phenyl]-4,4,4-trifluoro-3-methylbutanoyl}amino)phenyl]-2-methylpropanoic acid;

[1-(4-chloro-3-{[(2S,3R)-2-(4-chlorophenyl)-4,4,4-trifluoro-3-methylbutanoyl]amino}phenyl)-3,3-difluorocyclobutyl]acetic acid; or

(2S)-3-(4-Chloro-3-{[(4-chlorophenyl)(3,3-difluorocyclopentyl)acetyl]amino}phenyl)-2-methylpropanoic acid.

5. A process for preparing a compound according to claim 1 , wherein

(a) a carboxylic acid of the formula (II)

in which R 5A , R 5B , R 6 and R 7 have the meanings given in claim 1

is coupled with an amine of the formula (III)

in which R 1A , R 1B , R 2A , R 2B , R 3 and R 4 have the meanings given in claim 1

and

T 1 represents (C 1 -C 4 )-alkyl or benzyl,

to give a carboxamide of the formula (IV)

in which R 1A , R 1B , R 2A , R 2B , R 3 , R 4 , R 5A , R 5B , R 6 , R 7 and T 1 have the meanings given above,

(b) the ester radical T 1 is removed to give the compound of formula (I), and

(c) the compound of formula (I) is optionally separated into its enantiomers and/or diastereomers, and/or optionally reacted with one or more (i) solvents and/or (ii) bases to give a solvate, salt and/or solvate of a salt thereof.

6. The process according to claim 5 , wherein step (a) is performed via a carbonyl chloride intermediate in the presence of a base.

7. The process according to claim 5 , wherein in step (b) the ester radical T 1 is removed by basic or acidic solvolysis and, if T 1 represents benzyl, also by hydrogenolysis.

8. A pharmaceutical composition comprising a compound according to claim 1 and an inert, non-toxic, pharmaceutically suitable excipient.

9. A pharmaceutical composition comprising a compound according to claim 2 and an inert, non-toxic, pharmaceutically suitable excipient.

10. A pharmaceutical composition comprising a compound according to claim 3 and an inert, non-toxic, pharmaceutically suitable excipient.

11. A pharmaceutical composition comprising a compound according to claim 4 and an inert, non-toxic, pharmaceutically suitable excipient.

12. A pharmaceutical composition comprising a compound according to claim 1 in combination with one or more further active compounds selected from the group consisting of organic nitrates, NO donors, cGMP-PDE inhibitors, stimulators of guanylate cyclase, agents having antithrombotic activity, agents lowering blood pressure, and agents altering lipid metabolism.

13. A pharmaceutical composition comprising a compound according to claim 2 in combination with one or more further active compounds selected from the group consisting of organic nitrates, NO donors, cGMP-PDE inhibitors, stimulators of guanylate cyclase, agents having antithrombotic activity, agents lowering blood pressure, and agents altering lipid metabolism.

14. A pharmaceutical composition comprising a compound according to claim 3 in combination with one or more further active compounds selected from the group consisting of organic nitrates, NO donors, cGMP-PDE inhibitors, stimulators of guanylate cyclase, agents having antithrombotic activity, agents lowering blood pressure, and agents altering lipid metabolism.

15. A pharmaceutical composition comprising a compound according to claim 4 in combination with one or more further active compounds selected from the group consisting of organic nitrates, NO donors, cGMP-PDE inhibitors, stimulators of guanylate cyclase, agents having antithrombotic activity, agents lowering blood pressure, and agents altering lipid metabolism.

16. The process according to claim 5 , wherein step (a) is performed in the presence of an inert solvent with the aid of a condensing agent.