Acylamino-substituted fused cyclopentanecarboxylic acid derivatives and their use as pharmaceuticals

Abstract

The present invention relates to compounds of the formula I, wherein A, Y, Z, R 3 to R 6 , R 20 to R 22 and R 50 have the meanings indicated in the claims, which are valuable pharmaceutical active compounds. Specifically, they are inhibitors of the endothelial differentiation gene receptor 2 (Edg-2, EDG2), which is activated by lysophosphatidic acid (LPA) and is also termed as LPA 1 receptor, and are useful for the treatment of diseases such as atherosclerosis, myocardial infarction and heart failure, for example. The invention furthermore relates to processes for the preparation of the compounds of the formula I, their use and pharmaceutical compositions comprising them.

We claim: 
     
         1 . A compound of formula I, 
       
         
           
           
               
               
           
         
         wherein 
         ring A is a 3-membered to 7-membered cycloalkane ring, a benzene ring, or a monocyclic 5-membered or 6-membered aromatic heterocyclic ring which comprises 1 or 2 identical or different hetero ring members chosen from the series consisting of N, N(R 0 ), O and S, wherein the cycloalkane ring is optionally substituted by one or more identical or different substituents chosen from the series consisting of fluorine and (C 1 -C 4 )-alkyl, and the benzene ring and the heterocyclic rings are optionally substituted by one or more identical or different substituents chosen from the series consisting of halogen, R 1 , HO—, R 1 —O—, R 1 —C(O)—O—, R 1 —S(O) 2 —O—, R 1 —S(O) m —, H 2 N—, R 1 —NH—, R 1 —N(R 1 )—, R 1 —C(O)—NH—, R 1 —C(O)—N(R 71 )—, R 1 —S(O) 2 —NH—, R 1 —S(O) 2 —N(R 71 )—, R 1 —C(O)—, HO—C(O)—, R 1 —O—C(O)—, H 2 N—C(O)—, R 1 —NH—C(O)—, R 1 —N(R 1 )—C(O)—, H 2 N—S(O) 2 —, R 1 —NH—S(O) 2 —, R 1 —N(R 1 )—S(O) 2 —, NC—, O 2 N—, phenyl and Het; 
         Y is chosen from the series consisting of N(R 10 ), S, O, C(R 12 )═C(R 13 ), N═C(R 14 ) and C(R 15 )═N; 
         Z is chosen from the series consisting of N and C(R 16 ); 
         R 0  is chosen from the series consisting of hydrogen and R 2 ; 
         R 1 , R 2 , R 11 , R 30 , R 33 , R 35 , R 54 , R 55 , R 57  and R 58  are, independently of each other group R 1 , R 2 , R 11 , R 30 , R 33 , R 35 , R 54 , R 55 , R 57  and R 58 , chosen from the series consisting of (C 1 -C 6 )-alkyl, (C 2 -C 6 )-alkenyl, (C 2 -C 6 )-alkynyl, (C 3 -C 7 )-cycloalkyl and (C 3 -C 7 )-cycloalkyl-(C 1 -C 4 )-alkyl- which are all optionally substituted by one or more identical or different substituents R 70 ; 
         R 3  and R 5  are independently of each other chosen from the series consisting of hydrogen, (C 1 -C 4 )-alkyl, phenyl-(C 1 -C 4 )-alkyl-, phenyl and hydroxy; 
         R 4  and R 6  are independently of each other chosen from the series consisting of hydrogen and (C 1 -C 4 )-alkyl; 
         R 10  is chosen from the series consisting of hydrogen and R 11 ; 
         R 12 , R 13 , R 14 , R 15  and R 16  are independently of each other chosen from the series consisting of hydrogen, halogen, (C 1 -C 4 )-alkyl, HO—(C 1 -C 4 )-alkyl-, (C 1 -C 4 )-alkyl-O—, (C 1 -C 4 )-alkyl-S(O) m —, H 2 N—, (C 1 -C 4 )-alkyl-NH—, (C 1 -C 4 )-alkyl-N((C 1 -C 4 )-alkyl)-, (C 1 -C 4 )-alkyl-C(O)—, NC— and O 2 N—; 
         R 20  is chosen from the series consisting of hydrogen and (C 1 -C 4 )-alkyl; 
         one of the groups R 21  and R 22  is a group of the formula II
   R 24 —R 23 —  II
 
 
         and the other of the groups R 21  and R 22  is chosen from the series consisting of hydrogen, halogen, R 30 , HO—, R 30 —O—, R 30 —C(O)—O—, R 30 —S(O) 2 —O—, R 30 —S(O) m —, H 2 N—, R 30 —NH—, R 30 —N(R 30 )—, R 30 —C(O)—NH—, R 30 —C(O)—N(R 71 )—, R 30 —S(O) 2 —NH—, R 30 —S(O) 2 —N(R 71 )—, R 30 —C(O)—, HO—C(O)—, R 30 —O—C(O)—, H 2 N—C(O)—, R 30 —NH—C(O)—, R 30 —N(R 30 )—C(O)—, H 2 N—S(O) 2 —, R 30 —NH—S(O) 2 —, R 30 —N(R 30 )—S(O) 2 —, NC—, O 2 N— and Het 1 ; 
         R 23  is a direct bond or a chain consisting of 1 to 5 chain members of which 0, 1 or 2 chain members are identical or different hetero chain members chosen from the series consisting of N(R 25 ), O, S, S(O) and S(O) 2 , but two hetero chain members can be present in adjacent positions only if one of them is chosen from the series consisting of S(O) and S(O) 2  and the other is chosen from the series consisting of N(R 25 ), O and S, and the other chain members are identical or different groups C(R 26 )(R 26 ), wherein two adjacent groups C(R 26 )(R 26 ) can be connected to each other by a double bond or a triple bond; 
         R 24  is chosen from the series consisting of hydrogen, R 31 , HO—, R 31 —O—, R 31 —C(O)—O—, R 31 —S(O) m —, H 2 N—, R 31 —NH—, R 31 —N(R 31 )—, R 31 —C(O)—NH—, R 31 —C(O)—N(R 71 )—, R 31 —S(O) 2 —NH—, R 31 —S(O) 2 —N(R 71 )—, R 31 —C(O)—, HO—C(O)—, R 31 —O—C(O)—, H 2 N—C(O)—, R 31 —NH—C(O)—, R 31 —N(R 31 )—C(O)—, H 2 N—S(O) 2 —, R 31 —NH—S(O) 2 —, R 31 —N(R 31 )—S(O) 2 —, NC— and a 3-membered to 10-membered, monocyclic, bicyclic or tricyclic ring which is saturated or unsaturated and contains 0, 1, 2 or 3 identical or different hetero ring members chosen from the series consisting of N, N(R 32 ), O, S, S(O) and S(O) 2 , which ring is optionally substituted on ring carbon atoms by one or more identical or different substituents chosen from the series consisting of halogen, R 33 , HO—, R 33 —O—, R 33 —C(O)—O—, R 33 —S(O) 2 —O—, R 33 —S(O) m —, H 2 N—, R 33 —NH—, R 33 —N(R 33 )—, R 33 —C(O)—NH—, R 33 —C(O)—N(R 71 )—, R 33 —S(O) 2 —NH—, R 33 —S(O) 2 —N(R 71 )—, H 2 N—S(O) 2 —NH—, R 33 —NH—S(O) 2 —NH—, R 33 —N(R 33 )—S(O) 2 —NH—, H 2 N—S(O) 2 —N(R 71 )—, R 33 —NH—S(O) 2 —N(R 71 )—, R 33 —N(R 33 )—S(O) 2 —N(R 71 )—, R 33 —C(O)—, HO—C(O)—, R 33 —O—C(O)—, H 2 N—C(O)—, R 33 —NH—C(O)—, R 33 —N(R 33 )—C(O)—, H 2 N—S(O) 2 —, R 33 —NH—S(O) 2 —, R 33 —N(R 33 )—S(O) 2 —, NC—, O 2 N—, oxo, phenyl and Het, 
         provided that the total number of C, N, O and S atoms which is present in the two groups R 23  and R 24 , is at least 5; 
         R 25  is chosen from the series consisting of hydrogen and (C 1 -C 4 )-alkyl; 
         R 26 , independently of each other group R 26 , is chosen from the series consisting of hydrogen, fluorine, (C 1 -C 4 )-alkyl and HO—, or two groups R 26  bonded to the same carbon atom together are oxo, or two of the groups R 26  or one group R 25  and one group R 26 , together with the comprised chain members, form a 3-membered to 7-membered monocyclic ring which is saturated and contains 0, 1 or 2 identical or different hetero ring members chosen from the series consisting of N, N(R 34 ), O, S, S(O) and S(O) 2 , which ring is optionally substituted on ring carbon atoms by one more identical or different substituents chosen from the series consisting of fluorine and (C 1 -C 4 )-alkyl; 
         R 31  is chosen from the series consisting of (C 1 -C 6 )-alkyl, (C 2 -C 6 )-alkenyl and (C 2 -C 6 )-alkynyl which are all optionally substituted by one or more identical or different substituents R 70 ; 
         R 32  and R 34  are independently of each other chosen from the series consisting of hydrogen, R 35 , R 35 —S(O) 2 —, R 35 —C(O)—, R 35 —O—C(O)—, phenyl and Het; 
         R 50  is chosen from the series consisting of R 51 —O— and R 52 —N(R 53 )—; 
         R 51  is chosen from the series consisting of hydrogen and R 54 ; 
         R 52  is chosen from the series consisting of hydrogen, R 55 , NC— and R 56 —S(O) 2 —; 
         R 53  is chosen from the series consisting of hydrogen and R 57 ; 
         R 56  is chosen from the series consisting of R 58  and phenyl; 
         R 60 , independently of each other group R 60 , is chosen from the series consisting of hydrogen and (C 1 -C 4 )-alkyl; 
         R 70  is chosen from the series consisting of HO—, R 71 —O—, R 71 —C(O)—O—, R 71 —S(O) m —, H 2 N—, R 71 —NH—, R 71 —N(R 71 )—, R 71 —C(O)—NH—, R 71 —C(O)—N(R 71 )—, R 71 —S(O) 2 —NH—, R 71 —S(O) 2 —N(R 71 )—, HO—C(O)—, R 71 —O—C(O)—, H 2 N—C(O)—, R 71 —NH—C(O)—, R 71 —N(R 71 )—C(O)—, H 2 N—S(O) 2 —, R 71 —NH—S(O) 2 —, R 71 —N(R 71 )—S(O) 2 —, NC—, oxo, phenyl and Het 2 ; 
         R 71 , independently of each other group R 71 , is chosen from (C 1 -C 4 )-alkyl, (C 3 -C 4 )-cycloalkyl and (C 3 -C 4 )-cycloalkyl-(C 1 -C 2 )-alkyl-; 
         Het, independently of each other group Het, is a monocyclic 4-membered to 7-membered heterocyclic ring which comprises 1, 2 or 3 identical or different hetero ring members chosen from the series consisting of N, N(R 60 ), O, S, S(O) and S(O) 2 , which ring is saturated or unsaturated and is optionally substituted by one or more identical or different substituents chosen from the series consisting of halogen, (C 1 -C 4 )-alkyl and R 70 ; 
         Het 1  is a monocyclic 4-membered to 7-membered heterocyclic ring which comprises 1 or 2 identical or different hetero ring members chosen from the series consisting of N, N(R 60 ), O, S, S(O) and S(O) 2 , which ring is saturated and is optionally substituted by one or more identical or different substituents chosen from the series consisting of fluorine and (C 1 -C 4 )-alkyl; 
         Het 2  is a monocyclic 5-membered or 6-membered heterocyclic ring which comprises 1, 2 or 3 identical or different hetero ring members chosen from the series consisting of N, N(R 60 ), O and S, which ring is aromatic and is optionally substituted by one or more identical or different substituents chosen from the series consisting of halogen, (C 1 -C 4 )-alkyl, (C 1 -C 4 )-alkyl-O— and NC—; 
         m, independently of each other number m, is an integer chosen from the series consisting of 0, 1 and 2; 
         phenyl, independently of each other group phenyl, is optionally substituted by one or more identical or different substituents chosen from the series consisting of halogen, (C 1 -C 4 )-alkyl, (C 1 -C 4 )-alkyl-O— and NC—, unless specified otherwise; 
         cycloalkyl, independently of each other group cycloalkyl, and independently of any other substituents on cycloalkyl, is optionally substituted by one or more identical or different substituents chosen from fluorine and (C 1 -C 4 )-alkyl; and 
         alkyl, alkenyl and alkynyl, independently of each other group alkyl, alkenyl and alkynyl, and independently of any other substituents on alkyl, alkenyl and alkynyl, is optionally substituted by one or more fluorine substituents; 
         in any of its stereoisomeric forms or a mixture of stereoisomeric forms in any ratio, or a physiologically acceptable salt thereof, or a physiologically acceptable solvate of any of them, 
         provided that the compound of the formula I is not 2-[(6,2′,4′-trichlorobiphenyl-3-carbonyl)amino]indane-2-carboxylic acid, 2-[6-chloro-[1,1′,4′,1″]terphenyl-3-carbonyl)amino]indane-2-carboxylic acid, 2-(4-chloro-3-phenylethynyl-benzoylamino)-indane-2-carboxylic acid, 5-(4-chloro-phenyl)-2-[4-(2-methyl-1H-benzoimidazol-1-ylmethyl)-benzoylamino]-indane-2-carboxylic acid or 5-(4-chloro-phenyl)-2-[4-(2-methyl-1H-benzoimidazol-1-ylmethyl)-benzoylamino]-indane-2-carboxylic acid ethyl ester. 
       
     
     
         2 . The compound according to  claim 1 , wherein:
 R 3  and R 5  are independently of each other chosen from the series consisting of hydrogen, (C 1 -C 4 )-alkyl, phenyl-(C 1 -C 4 )-alkyl- and phenyl;   in any of its stereoisomeric forms or a mixture of stereoisomeric forms in any ratio, or a physiologically acceptable salt thereof, or a physiologically acceptable solvate of any of them.   
     
     
         3 . The compound according to  claim 1 , wherein:
 ring A is a cyclohexane ring, a benzene ring, a pyridine ring, a pyridazine ring or a thiophene ring, wherein the cyclohexane ring is optionally substituted by one or more identical or different substituents chosen from the series consisting of fluorine and (C 1 -C 4 )-alkyl, and the benzene ring, the pyridine ring, the pyridazine ring and the thiophene ring are optionally substituted by one or more identical or different substituents chosen from the series consisting of halogen, R 1 , HO—, R 1 —O—, R 1 —C(O)—O—, R 1 —S(O) 2 —O—, R 1 —S(O) m —, H 2 N—, R 1 —NH—, R 1 —N(R 1 )—, R 1 —C(O)—NH—, R 1 —C(O)—N(R 71 )—, R 1 —S(O) 2 —NH—, R 1 —S(O) 2 —N(R 71 )—, R 1 —C(O)—, HO—C(O)—, R 1 —O—C(O)—, H 2 N—C(O)—, R 1 —NH—C(O)—, R 1 —N(R 1 )—C(O)—, H 2 N—S(O) 2 —, R 1 —NH—S(O) 2 —, R 1 —N(R 1 )—S(O) 2 —, NC— and O 2 N—;   Y is chosen from the series consisting of S, C(R 12 )═C(R 13 ), and C(R 15 )═N; and   Z is C(R 16 );   in any of its stereoisomeric forms or a mixture of stereoisomeric forms in any ratio, or a physiologically acceptable salt thereof, or a physiologically acceptable solvate of any of them.   
     
     
         4 . The compound according to  claim 1 , wherein:
 ring A is a benzene ring, a pyridine ring, a pyrazine or a thiophene ring which rings are all optionally substituted by one or two identical or different substituents chosen from the series consisting of halogen, (C 1 -C 4 )-alkyl and (C 1 -C 4 )-alkyl-O—;   Y is chosen from the series consisting of S, C(R 12 )═C(R 13 ) and C(R 15 )═N;   Z is C(R 16 );   R 3  and R 5  are independently of each other chosen from the series consisting of hydrogen and (C 1 -C 4 )-alkyl;   R 4  and R 6  are hydrogen;   R 12 , R 13 , R 15  and R 16  are independently of each other chosen from the series consisting of hydrogen, halogen (C 1 -C 4 )-alkyl, (C 1 -C 4 )-alkyl-O— and NC—; and   R 20  is hydrogen;   in any of its stereoisomeric forms or a mixture of stereoisomeric forms in any ratio, or a physiologically acceptable salt thereof, or a physiologically acceptable solvate of any of them.   
     
     
         5 . The compound according to  claim 1 , wherein:
 R 21  is chosen from the series consisting of hydrogen, halogen, (C 1 -C 4 )-alkyl, HO—(C 1 -C 4 )-alkyl-, (C 1 -C 4 )-alkyl-O—, (C 1 -C 4 )-alkyl-S(O) m —, H 2 N—, (C 1 -C 4 )-alkyl-NH—, di((C 1 -C 4 )-alkyl)N—, (C 1 -C 4 )-alkyl-C(O)— and NC—;   R 22  is a group of the formula II;
   R 24 —R 23 —  II
 
   R 23  is a direct bond or a chain consisting of 2, 3 or 4 chain members of which 0 or 1 chain members are hetero chain members chosen from the series consisting of N(R 25 ), O, S, S(O) and S(O) 2 , and the other chain members are identical or different groups C(R 26 )(R 26 ), wherein two adjacent groups C(R 26 )(R 26 ) can be connected to each other by a double bond or a triple bond;   in any of its stereoisomeric forms or a mixture of stereoisomeric forms in any ratio, or a physiologically acceptable salt thereof, or a physiologically acceptable solvate of any of them.   
     
     
         6 . The compound according to  claim 1 , wherein:
 R 24  is a 3-membered to 7-membered monocyclic ring or a 7-membered to 10-membered bicyclic ring, which rings are saturated or unsaturated and contain 0, 1 or 2 identical or different hetero ring members chosen from the series consisting of N, N(R 32 ), O, S, S(O) and S(O) 2 , and which rings are optionally substituted on ring carbon atoms by one or more identical or different substituents chosen from the series consisting of halogen, R 33 , HO—, R 33 —O—, R 33 —S(O) m —, H 2 N—, R 33 —NH—, R 33 —N(R 33 )—, R 33 —C(O)—NH—, R 33 —C(O)—N(R 71 )—, R 33 —S(O) 2 —NH—, R 33 —S(O) 2 —N(R 71 )—, H 2 N—S(O) 2 —NH—, R 33 —NH—S(O) 2 —NH—, R 33 —N(R 33 )—S(O) 2 —NH—, H 2 N—S(O) 2 —N(R 71 )—, R 33 —NH—S(O) 2 —N(R 71 )—, R 33 —N(R 33 )—S(O) 2 —N(R 71 )—, HO—C(O)—, R 33 —O—C(O)—, H 2 N—C(O)—, R 33 —NH—C(O)—, R 33 —N(R 33 )—C(O)—, NC—, oxo, phenyl and Het; and   R 32  is chosen from the series consisting of hydrogen, R 35 , R 35 —C(O)—, R 35 —O—C(O)— and phenyl;   in any of its stereoisomeric forms or a mixture of stereoisomeric forms in any ratio, or a physiologically acceptable salt thereof, or a physiologically acceptable solvate of any of them.   
     
     
         7 . The compound according to  claim 1 , wherein:
 ring A is a benzene ring, a pyridine ring, a pyrazine or a thiophene ring which rings are all optionally substituted by one or two identical or different substituents chosen from the series consisting of halogen, (C 1 -C 4 )-alkyl and (C 1 -C 4 )-alkyl-O—;   Y is chosen from the series consisting of S, C(R 12 )═C(R 13 ) and C(R 15 )═N;   Z is C(R 16 );   R 3  and R 5  are independently of each other chosen from the series consisting of hydrogen and (C 1 -C 4 )-alkyl;   R 4  and R 6  are hydrogen;   R 12 , R 13 , R 15  and R 16  are independently of each other chosen from the series consisting of hydrogen, halogen (C 1 -C 4 )-alkyl, (C 1 -C 4 )-alkyl-O— and NC—;   R 20  is hydrogen;   R 21  is chosen from the series consisting of hydrogen, halogen, (C 1 -C 4 )-alkyl, HO—(C 1 -C 4 )-alkyl-, (C 1 -C 4 )-alkyl-O—, (C 1 -C 4 )-alkyl-S(O) m —, H 2 N—, (C 1 -C 4 )-alkyl-NH—, di((C 1 -C 4 )-alkyl)N—, (C 1 -C 4 )-alkyl-C(O)— and NC—;   R 22  is a group of the formula II;
   R 24 —R 23 —  II
 
   R 23  is a direct bond or a chain consisting of 2, 3 or 4 chain members of which 0 or 1 chain members are hetero chain members chosen from the series consisting of N(R 25 ), O, S, S(O) and S(O) 2 , and the other chain members are identical or different groups C(R 26 )(R 26 ), wherein two adjacent groups C(R 26 )(R 26 ) can be connected to each other by a double bond or a triple bond;   R 24  is a 3-membered to 7-membered monocyclic ring or a 7-membered to 10-membered bicyclic ring, which rings are saturated or unsaturated and contains 0, 1 or 2 identical or different hetero ring members chosen from the series consisting of N, N(R 32 ), O, S, S(O) and S(O) 2 , which ring is optionally substituted on ring carbon atoms by one or more identical or different substituents chosen from the series consisting of halogen, R 33 , HO—, R 33 —O—, R 33 —S(O) m —, H 2 N—, R 33 —NH—, R 33 —N(R 33 )—, R 33 —C(O)—NH—, R 33 —C(O)—N(R 71 )—, R 33 —S(O) 2 —NH—, R 33 —S(O) 2 —N(R 71 )—, HO—C(O)—, R 33 —O—C(O)—, H 2 N—C(O)—, R 33 —NH—C(O)—, R 33 —N(R 33 )—C(O)—, NC—, oxo, phenyl and Het; and   R 32  is chosen from the series consisting of hydrogen, R 35 , R 35 —C(O)—, R 35 —O—C(O)— and phenyl;   in any of its stereoisomeric forms or a mixture of stereoisomeric forms in any ratio, or a physiologically acceptable salt thereof, or a physiologically acceptable solvate of any of them.   
     
     
         8 . The compound according to  claim 1 , wherein
 ring A is a benzene ring which is optionally substituted by one or two identical or different substituents chosen from the series consisting of halogen, (C 1 -C 4 )-alkyl and (C 1 -C 4 )-alkyl-O—;   Y is C(R 12 )═C(R 13 );   Z is C(R 16 );   R 3 , R 4 , R 5  and R 6  are hydrogen;   R 12 , R 13  and R 16  are independently of each other chosen from the series consisting of hydrogen, halogen, (C 1 -C 4 )-alkyl, (C 1 -C 4 )-alkyl-O— and NC—;   R 20  is hydrogen;   R 21  is chosen from the series consisting of hydrogen, halogen, (C 1 -C 4 )-alkyl, HO—(C 1 -C 4 )-alkyl-, (C 1 -C 4 )-alkyl-O—, (C 1 -C 4 )-alkyl-S(O) m —, (C 1 -C 4 )-alkyl-C(O)— and NC—;   R 22  is a group of the formula II;
   R 24 —R 23 —  II
 
   R 23  is a direct bond or a chain consisting of 2, 3 or 4 chain members of which 0 or 1 chain members are hetero chain members chosen from the series consisting of N(R 25 ), O, S, S(O) and S(O) 2 , and the other chain members are identical or different groups C(R 26 )(R 26 );   R 24  is a benzene ring which is optionally substituted by one or more identical or different substituents chosen from the series consisting of halogen, R 33 , HO—, R 33 —O—, R 33 —S(O) m —, H 2 N—, R 33 —NH—, R 33 —N(R 33 )—, R 33 —C(O)—NH—, R 33 —S(O) 2 —NH—, HO—C(O)—, R 33 —O—C(O)—, H 2 N—C(O)—, R 33 —NH—C(O)—, R 33 —N(R 33 )—C(O)— and NC—;   provided that the total number of C, N, O and S atoms which is present in the two groups R 23  and R 24 , is at least 5;   R 25  is chosen from the series consisting of hydrogen and (C 1 -C 4 )-alkyl;   R 26 , independently of each other group R 26 , is chosen from the series consisting of hydrogen, fluorine, (C 1 -C 4 )-alkyl and HO—, or two of the groups R 26  which are bonded to the same carbon atom in the chain, together with the carbon atom carrying them, form a cyclopropane ring;   R 33  is, independently of each other group R 33 , chosen from the series consisting of (C 3 -C 7 )-cycloalkyl and (C 3 -C 7 )-cycloalkyl-(C 1 -C 2 )-alkyl-, which are all optionally substituted by one or more identical or different substituents R 70 ;   R 50  is chosen from the series consisting of R 51 —O— and R 52 —N(R 53 )—;   R 51  is chosen from the series consisting of hydrogen and (C 1 -C 4 )-alkyl;   R 52  is chosen from the series consisting of hydrogen and (C 1 -C 4 )-alkyl;   R 53  is chosen from the series consisting of hydrogen and (C 1 -C 4 )-alkyl;   R 70  is chosen from the series consisting of HO— and R 71 —O—;   R 71  is (C 1 -C 4 )-alkyl;   m, independently of each other number m, is an integer chosen from the series consisting of 0 and 2;   cycloalkyl, independently of each other group cycloalkyl, and independently of any other substituents on cycloalkyl, is optionally substituted by one or more identical or different substituents chosen from fluorine and (C 1 -C 4 )-alkyl; and   alkyl, independently of each other group alkyl, and independently of any other substituents on alkyl, is optionally substituted by one or more fluorine substituents;   in any of its stereoisomeric forms or a mixture of stereoisomeric forms in any ratio, or a physiologically acceptable salt thereof, or a physiologically acceptable solvate of any of them.   
     
     
         9 . The compound according to  claim 1 , which is
 2-[4-methylsulfanyl-3-(2-m-tolyl-ethoxy)-benzoylamino]-indane-2-carboxylic acid,   2-[4-acetyl-3-(2-m-tolyl-ethoxy)-benzoylamino]-indane-2-carboxylic acid,   2-[4-ethyl-3-(2-m-tolyl-ethoxy)-benzoylamino]-indane-2-carboxylic acid,   2-[4-ethoxy-3-(2-m-tolyl-ethoxy)-benzoylamino]-indane-2-carboxylic acid,   2-[4-methoxy-3-(2-m-tolyl-ethoxy)-benzoylamino]-indane-2-carboxylic acid,   2-{4-methoxy-3-[2-(3-trifluoromethylsulfanyl-phenyl)-ethoxy]-benzoylamino}-indane-2-carboxylic acid,   2-[4-methoxy-3-(1-m-tolyl-cyclopropylmethoxy)-benzoylamino]-indane-2-carboxylic acid,   2-{3-[2-(3-cyano-phenyl)-ethoxy]-4-methoxy-benzoylamino}-indane-2-carboxylic acid,   5-[4-methoxy-3-(2-m-tolyl-ethoxy)-benzoylamino]-5,6-dihydro-4H-cyclopenta[b]thiophene-5-carboxylic acid,   2-{[5-acetyl-4-(2-m-tolyl-ethoxy)-thiophene-2-carbonyl]-amino}-indane-2-carboxylic acid,   2-[3-fluoro-4-methoxy-5-(2-m-tolyl-ethoxy)-benzoylamino]-indane-2-carboxylic acid,   2-[4-methoxy-3-(2-m-tolyloxy-ethyl)-benzoylamino]-indane-2-carboxylic acid,   2-[4-methoxy-3-(3-m-tolyl-propyl)-benzoylamino]-indane-2-carboxylic acid,   5-fluoro-2-[4-methoxy-3-(2-m-tolyl-ethoxy)-benzoylamino]-indane-2-carboxylic acid,   2-[4-methoxy-3-(2-m-tolyl-ethoxy)-benzoylamino]-5,6-dimethyl-indane-2-carboxylic acid,   2-[4-cyano-3-(2-m-tolyl-ethoxy)-benzoylamino]-indane-2-carboxylic acid,   2-[4-methoxy-3-(2-m-tolyl-ethylamino)-benzoylamino]-indane-2-carboxylic acid,   2-{3-[2-(3-chloro-phenyl)-ethoxy]-4-methyl-benzoylamino}-indane-2-carboxylic acid,   2-[4-methoxy-3-(2-m-tolyl-ethylsulfanyl)-benzoylamino]-indane-2-carboxylic acid,   2-[3-(2-m-tolyl-ethoxy)-4-trifluoromethyl-benzoylamino]-indane-2-carboxylic acid,   2-{3-[2-(2-fluoro-5-methyl-phenyl)-ethoxy]-4-trifluoromethyl-benzoylamino}-indane-2-carboxylic acid,   2-(3-{2-[3-(2-hydroxy-ethyl)-phenyl]-ethoxy}-4-methoxy-benzoylamino)-indane-2-carboxylic acid,   2-{[6-methoxy-5-(2-m-tolyl-ethoxy)-pyridine-3-carbonyl]-amino}-indane-2-carboxylic acid,   2-[(3′-methanesulfonylamino-6-methoxy-biphenyl-3-carbonyl)-amino]-indane-2-carboxylic acid,   2-[(3′-dimethylaminosulfonylamino-6-methoxy-biphenyl-3-carbonyl)-amino]-indane-2-carboxylic acid,   2-[(6-methoxy-3′-trifluoromethoxy-biphenyl-3-carbonyl)-amino]-indane-2-carboxylic acid,   2-[(3′-cyanomethyl-6-methoxy-biphenyl-3-carbonyl)-amino]-indane-2-carboxylic acid,   2-[(3′-isopropyl-6-methoxy-biphenyl-3-carbonyl)-amino]-indane-2-carboxylic acid,   2-[(3-chloro-6-methoxy-Z-methyl-biphenyl-3-carbonyl)-amino]-indane-2-carboxylic acid,   2-{[5-(3-chloro-phenyl)-6-methoxy-pyridine-3-carbonyl]-amino}-indane-2-carboxylic acid, or   2-[3-(2,2-difluoro-2-phenyl-ethoxy)-4-methoxy-benzoylamino]-indane-2-carboxylic acid;   in any of its stereoisomeric forms or a mixture of stereoisomeric forms in any ratio, or a physiologically acceptable salt thereof, or a physiologically acceptable solvate of any of them.   
     
     
         10 . A process for the compound according to  claim 1 , comprising reacting a compound of formula III with a compound of the formula IV, 
       
         
           
           
               
               
           
         
         wherein the ring A and the groups Y, Z, R 3  to R 6 , R 20  to R 22  and R 50  in the compounds of the formulae III and IV are defined as in  claim 1  and additionally functional groups can be present in protected form or in the form of a precursor group, and the group G in the compound of the formula IV is HO—, (C 1 -C 4 )-alkyl-O— or halogen. 
       
     
     
         11 . A pharmaceutical composition comprising the compound according to  claim 1 , in any of its stereoisomeric forms or a mixture of stereoisomeric forms in any ratio, or a physiologically acceptable salt thereof, or a physiologically acceptable solvate of any of them, and a pharmaceutically acceptable carrier. 
     
     
         12 . A pharmaceutical composition comprising the compound according to  claim 9 , in any of its stereoisomeric forms or a mixture of stereoisomeric forms in any ratio, or a physiologically acceptable salt thereof, or a physiologically acceptable solvate of any of them, and a pharmaceutically acceptable carrier. 
     
     
         13 . A method for treating a cardiovascular disease, heart failure, cardiomyopathy, myocardial infarction, myocardial remodeling, vascular remodeling, hypertension, atherosclerosis, peripheral arterial occlusive disease, restenosis, thrombosis, vascular permeability disorder, an inflammatory disease, rheumatoid arthritis, osteoarthritis, renal disease, renal papillary necrosis, renal failure, a pulmonary disease, chronic obstructive pulmonary disease, asthma, acute respiratory dystress syndrome, an immunological disease, an allergic disease, tumor growth, metastasis, a metabolic disease, a fibrotic disease, pulmonary fibrosis, cardiac fibrosis, vascular fibrosis, perivascular fibrosis, renal fibrosis, liver fibrosis, fibrosing skin condition, psoriasis, pain, pruritus, retinal ischemia, reperfusion damage, macular degeneration, a psychiatric disorder, a neurodegenerative disease, a cerebral nerve disorder, a peripheral nerve disorder, an endocrinic disorder, hyperthyroidism, a scarring disorder or a would healing disorder, or for cardioprotection or renoprotection, in a patient in need thereof, comprising administering to the patient a pharmaceutically effective amount of the compound according to  claim 1 , in any of its stereoisomeric forms or a mixture of stereoisomeric forms in any ratio, or a physiologically acceptable salt thereof, or a physiologically acceptable solvate of any of them. 
     
     
         14 . A method for treating a cardiovascular disease, heart failure, cardiomyopathy, myocardial infarction, myocardial remodeling, vascular remodeling, hypertension, atherosclerosis, peripheral arterial occlusive disease, restenosis, thrombosis, vascular permeability disorder, an inflammatory disease, rheumatoid arthritis, osteoarthritis, renal disease, renal papillary necrosis, renal failure, a pulmonary disease, chronic obstructive pulmonary disease, asthma, acute respiratory dystress syndrome, an immunological disease, an allergic disease, tumor growth, metastasis, a metabolic disease, a fibrotic disease, pulmonary fibrosis, cardiac fibrosis, vascular fibrosis, perivascular fibrosis, renal fibrosis, liver fibrosis, fibrosing skin condition, psoriasis, pain, pruritus, retinal ischemia, reperfusion damage, macular degeneration, a psychiatric disorder, a neurodegenerative disease, a cerebral nerve disorder, a peripheral nerve disorder, an endocrinic disorder, hyperthyroidism, a scarring disorder or a would healing disorder, or for cardioprotection or renoprotection, in a patient in need thereof, comprising administering to the patient a pharmaceutically effective amount of the compound according to  claim 9 , in any of its stereoisomeric forms or a mixture of stereoisomeric forms in any ratio, or a physiologically acceptable salt thereof, or a physiologically acceptable solvate of any of them.