(carboxylalkylenephenyl)phenyloxamides, method for the production thereof and use of same as a medicament

Abstract

The invention relates to (carboxylalkylenephenyl)phenyloxamides and their physiologically tolerated salts, and their use as a medicament.

1 - 18 . (canceled) 
     
     
         19 . A method for lowering blood glucose, for treating diabetes, a CNS disorder, schizophrenia, or Alzheimer's disease, or for increasing insulin secretion, in a patient in need thereof, comprising administering to the patient a pharmaceutically effective amount of the compound according to formula I 
       
         
           
           
               
               
           
         
         wherein: 
         R3 is H, F, Cl, Br, CN, CF 3 , OH, OCF 3 , OCHF 2 , SCH 3 , SCF 3 , phenyl, Ophenyl, COOH, COO—(C 1 -C 6 )-alkyl, CO—(C 1 -C 6 )-alkyl, (C 1 -C 6 )-alkyl, (C 3 -C 8 )-cycloalkyl, O—(C 1 -C 6 ) alkyl, OBn, SO 2 —(C 1 -C 4 )-alkyl, SO 3 H SO 2 NR9R10, NR9R10 or SO 2 —N-piperidinyl, wherein the alkyl and phenyl are optionally substituted one or more times by R12; 
         R1 and R5 are, independently, H, F, Cl, Br, CN, CF 3 , SCH 3 , SCF 3 , phenyl, O-phenyl, COOH, COO—(C 1 -C 6 )-alkyl, CO—(C 1 -C 6 )-alkyl, (C 1 -C 6 )-alkyl, SO 2 —(C 1 -C 4 )-alkyl, SO 3 H, SO 2 NR9R10, NR9R10 or SO 2 —N-piperidinyl, wherein the alkyl and phenyl are optionally substituted one or more times by R12; 
         R2 and R4 are, independently, H, F, Cl, Br, CN, CF 3 , OCF 3 , OCHF 2 , SCH 3 , SCF 3 , phenyl, O-phenyl, COOH, COO—(C 1 -C 6 )-alkyl, CO—(C 1 -C 6 )-alkyl, (C 1 -C 6 )-alkyl, O—(C 1 -C 6 )-alkyl, O-Bn, SO 2 —(C 1 -C 4 )-alkyl, SO 3 H, SO 2 NR9R10, NR9R10 or SO 2 —N-piperidinyl, wherein the alkyl and phenyl are optionally substituted one or more times by R12; 
         R7 and R8 are, independently, H or (C 1 -C 6 )-alkyl; 
         X is (C 2 -C 3 )-alkylene optionally substituted one or more times by R11; 
         m is 0, 1, 2, 3 or 4; 
         R6 is OH, F, Cl, Br, CN, OCH 3 , OCF 3 , CH 3 , CF 3 , (C 1 -C 6 )-alkyl or O—(C 1 -C 6 )-alkyl, wherein the alkyl is optionally substituted one or more times by OH, F, Cl, Br or CN; 
         R9 and R10 are, independently, H, (C 1 -C 6 )-alkyl or phenyl, wherein the alkyl is optionally substituted one or more times by F, Cl or Br, and the phenyl is optionally substituted one or more times by R6; 
         R11 is F, Cl, Br, CN, OH, O—(C 1 -C 6 )-alkyl, (C 1 -C 6 )-alkyl, (C 2 -C 6 )-alkenyl, (C 2 -C 6 )-alkynyl or NR9R10; and 
         R12 is F, Cl, Br, CN, OH, O—(C 1 -C 6 )-alkyl, (C 1 -C 6 )-alkyl, (C 2 -C 6 )-alkenyl, (C 2 -C 6 )-alkynyl, NR9R10, COOH, COO—(C 1 -C 4 )-alkyl, SCH 3 , SCF 3 , SO 2 —(C 1 -C 4 )-alkyl, SO 3 H or SO 2 NR9R10; 
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         20 . (canceled) 
     
     
         21 . The method according to  claim 19 , wherein
 R3 is H, F, Cl, Br, CF 3 , OCF 3 , COOH, COO—(C 1 -C 6 )-alkyl, (C 1 -C 6 )-alkyl, (C 3 -C 8 )-Cycloalkyl, phenyl, or O-phenyl, wherein the alkyl and phenyl are optionally substituted one or more times by R12;   R1 and R5 are, independently, H, F, Cl, Br, CF 3 , COOH, COO—(C 1 -C 6 )-alkyl, (C 1 -C 6 )-alkyl, phenyl, or Ophenyl, wherein the alkyl and phenyl are optionally substituted one or more times by R12;   R2 and R4 are, independently, H, F, Cl, Br, CF 3 , COOH, COO—(C 1 -C 6 )-alkyl, or (C 1 -C 6 )-alkyl;   R7 and R8 are H;   m is 0; and   R12 is F, Cl, Br, CN, OH, O—(C 1 -C 6 )-alkyl, (C 1 -C 6 )-alkyl, (C 2 -C 6 )-alkenyl, (C 2 -C 6 )-alkynyl, NR9R10, COOH, or COO—(C 1 -C 4 )-alkyl;   
       or a pharmaceutically acceptable salt thereof. 
     
     
         22 . The method according to  claim 19 , wherein
 R3 is H, F, Cl, Br, CF 3 , OCF 3 , COOH, COO—(C 1 -C 6 )-alkyl, (C 1 -C 6 )-alkyl, (C 3 -C 8 )-cycloalkyl, or phenyl;   R1 and R5 are, independently, H, F, Cl, Br, CF 3 , COOH, COO—(C 1 -C 6 )-alkyl, (C 1 -C 6 )-alkyl, or phenyl;   R2 and R4 are, independently, H, F, Cl, Br, CF 3 , COOH, COO—(C 1 -C 6 )-alkyl, or (C 1 -C 6 )-alkyl;   R7 and R8 are H;   m is 0; and   R11 is (C 2 -C 6 )-alkynyl;   
       or a pharmaceutically acceptable salt thereof. 
     
     
         23 . The method according to  claim 19 , wherein
 R3 is H, F, Cl, Br, CF 3 , OCF 3 , COOH, COO—(C 1 -C 6 )-alkyl, (C 1 -C 6 )-alkyl, (C 3 -C 8 )-cycloalkyl, or phenyl;   R1 and R5 are, independently, H, F, Cl, Br, CF 3 , COOH, COO—(C 1 -C 6 )-alkyl, (C 1 -C 6 )-alkyl, or phenyl;   R2 and R4 are, independently, H, F, Cl, Br, CF 3 , COOH, COO—(C 1 -C 6 )-alkyl, or (C 1 -C 6 )-alkyl;   R7 and R8 are H;   X is (C 2 -C 3 )-alkylene, where X is linked at position 4 to the ring; and   m is 0;   
       or a pharmaceutically acceptable salt thereof. 
     
     
         24 . The method according to  claim 19 , wherein
 R3 is H, F, Cl, Br, CN, CF 3 , OH, OCF 3 , OCHF 2 , SCH 3 , SCF 3 , phenyl, O-phenyl, COOH, COO—(C 1 -C 6 )-alkyl, CO—(C 1 -C 6 )-alkyl, (C 1 -C 6 )-alkyl, O—(C 1 -C 6 )-alkyl, O-Bn, SO 2 —(C 1 -C 4 )-alkyl, SO 3 H, SO 2 NR9R10, NR9R10 or SO 2 —N-piperidinyl, wherein the alkyl and phenyl are optionally substituted one or more times by R12;   
       or a pharmaceutically acceptable salt thereof. 
     
     
         25 . The method according to  claim 19 , wherein
 R3 is H, F, Cl, Br, CF 3 , OCF 3 , COOH, COO—(C 1 -C 6 )-alkyl, (C 1 -C 6 )-alkyl, phenyl, or O-phenyl, wherein the alkyl and phenyl are optionally substituted one or more times by R12;   R1 and R5 are, independently, H, F, Cl, Br, CF 3 , COOH, COO—(C 1 -C 6 )-alkyl, (C 1 -C 6 )-alkyl, phenyl, or O-phenyl, wherein the alkyl and phenyl are optionally substituted one or more times by R12;   R2 and R4 are, independently, H, F, Cl, Br, CF 3 , COOH, COO—(C 1 -C 6 )-alkyl, or (C 1 -C 6 )-alkyl;   R7 and R8 are H;   m is 0; and   R12 is F, Cl, Br, CN, OH, O—(C 1 -C 6 )-alkyl, (C 1 -C 6 )-alkyl, (C 2 -C 6 )-alkenyl, (C 2 -C 6 )-alkynyl, NR9R10, COOH, or COO—(C 1 -C 4 )-alkyl;   
       or a pharmaceutically acceptable salt thereof. 
     
     
         26 . The method according to  claim 19 , wherein
 R3 is H, F, Cl, Br, CF 3 , OCF 3 , COOH, COO—(C 1 -C 6 )-alkyl, (C 1 -C 6 )-alkyl, or phenyl;   R1 and R5 are, independently, H, F, Cl, Br, CF 3 , COOH, COO—(C 1 -C 6 )-alkyl, (C 1 -C 6 )-alkyl, or phenyl;   R2 and R4 are, independently, H, F, Cl, Br, CF 3 , COOH, COO—(C 1 -C 6 )-alkyl, or (C 1 -C 6 )-alkyl;   R7 and R8 are H;   X is (C 2 -C 3 )-alkylene; and   m is 0;   
       or a pharmaceutically acceptable salt thereof. 
     
     
         27 . The method according to  claim 19 , wherein
 R3 is H, F, Cl, Br, CF 3 , OCF 3 , COOH, COO—(C 1 -C 6 )-alkyl, or (C 1 -C 6 )-alkyl;   R1 and R5 are, independently, H, F, Cl, Br, CF 3 , COOH, COO—(C 1 -C 6 )-alkyl, (C 1 -C 6 )-alkyl, or phenyl;   R2 and R4 are, independently, H, F, Cl, Br, CF 3 , COOH, COO—(C 1 -C 6 )-alkyl, or (C 1 -C 6 )-alkyl;   R7 and R8 are H;   X is (C 2 -C 3 )-alkylene, where X is linked at position 4 to the ring; and   m is 0;   
       or a pharmaceutically acceptable salt thereof.