Cinnamic acid amides

Abstract

The present invention relates to compounds, to processes for preparing them, to pharmaceutical compositions comprising them, and to their use in the therapy and/or prophylaxis in illnesses in people or animals, especially diseases of bacterial infection.

1 . A compound of the formula (I), 
     
       
         
         
             
             
         
       
     
     in which
 R 1  is hydrogen, methyl or halogen; 
 R 1′  is hydrogen, methyl or halogen; 
 R 2  is hydrogen or methyl; 
 R 3  is hydrogen, hydroxyl, amino, C 1 -C 3  alkyl, C 1 -C 3  alkoxy, benzyloxy, C 1 -C 3  alkylamino, C 1 -C 3  alkylcarbonylamino, phenylcarbonylamino or benzyl-carbonylamino 
 R 4  is hydrogen or C 1 -C 3  alkyl; 
 n is 2 or 3, 
 when n is 2: 
 two substituents R 5  together with the carbon atoms to which they are attached form a dioxine ring fused to the B ring, which may be substituted by 0, 1 or 2 substituents R 5-1 , the substituents R 5-1  being selected independently of one another from the group consisting of halogen, nitro, amino, trifluoromethyl, hydroxyl and alkoxy; 
 when n is 3: 
 one substitutent R 5  is halogen, trifluoromethyl, trifluoromethoxy, nitro, amino, alkylamino, hydroxyl, alkyl, alkoxy, carboxyl, alkoxycarbonyl, benzyloxycarbonyl, aminocarbonyl, alkylaminocarbonyl, aryl or heteroaryl, 
 and 
 two substituents R 5  together with the carbon atoms to which they are attached form a dioxine ring fused to the B ring, which may be substituted by 0, 1 or 2 substituents R 5-1 , the substituents R 5-1  being selected independently of one another from the group consisting of halogen, nitro, amino, trifluoromethyl, hydroxyl and alkoxy; 
 R 6  is alkyl, cycloalkyl or cycloalkenyl; 
 it being possible for R 6  to be substituted by 0, 1, 2 or 3 substituents R 6-1 , the substituents R 6-1  being selected independently of one another from the group consisting of halogen, nitro, amino, trifluoromethyl, hydroxyl, alkyl and alkoxy; 
 m is a number 1, 2 or 3; 
 A is aryl or heteroaryl,
 it being possible for A to be substituted by 0, 1, 2 or 3 substituents R A , the substituents R A  being selected independently of one another from the group consisting of halogen, alkyl, nitro, amino, cyano, trifluoromethyl, aryl, heteroaryl, hydroxyl, alkoxy, alkyl-amino, carboxyl, alkoxycarbonyl, aminocarbonyl, alkyl-carbonylamino and alkyl-amino-carbonyl, 
 
 or 
 two substituents R A  together with the carbon atoms to which they are attached form a dioxolane ring fused to the A ring, which may be substituted by 0, 1 or 2 substituents R A-1 , the substituents R A-1  being selected independently of one another from the group consisting of halogen, nitro, amino, trifluoromethyl, hydroxyl and alkoxy; 
 B is aryl or heteroaryl; 
 or a pharmaceutically acceptable salt, solvate or hydrate thereof. 
 
   
   
       2 - 20 . (canceled) 
   
   
       21 . A compound as claimed in  claim 1 , characterized in that
 R 1  is hydrogen or methyl;   R 1′  is hydrogen, methyl or fluorine;   R 2  is hydrogen;   R 3  is hydrogen, amino, C 1 -C 3  alkyl, C 1 -C 3  alkoxy, benzyloxy, C 1 -C 3  alkylamino, C 1 -C 3  alkylcarbonylamino, phenylcarbonylamino or benzylcarbonylamino;   R 4  is methyl;   two substituents R 5  together with the carbon atoms to which they are attached form a dioxine ring fused to the B ring;   R 6  is C 2 -C 7  alkyl, C 3 -C 7  cycloalkyl or C 5 -C 7  cycloalkenyl,   it being possible for R 6  to be substituted by 0, 1 or 2 substituent R 6-1 , R 6-1  being selected from the group consisting of halogen, trifluoromethyl, alkyl and methoxy,   m is a number 1 or 2;   A is phenyl, naphthyl or 5-, 6- or 10-membered heteroaryl,   it being possible for A to be substituted by 0, 1 or 2 substituents R A , the substituents R A  being selected independently of one another from the group consisting of halogen, alkyl, amino, cyano, trifluoromethyl, aryl, heteroaryl, hydroxyl, alkoxy, alkylamino, alkoxycarbonyl and aminocarbonyl,   or   two substituents R A  together with the carbon atoms to which they are attached form a dioxolane ring fused to the R A  ring, which may be substituted by 0 or 1 substituents R A-1 , the substituents R A-1  being selected independently of one another from the group consisting of halogen, nitro, amino, trifluoromethyl, hydroxyl and alkoxy;   B is phenyl, naphthyl or 5-, 6-, 9- or 10-membered heteroaryl.   
   
   
       22 . A compound as claimed in one of  claims 1  or  21 , characterized in that it conforms to formula (Ia) 
     
       
         
         
             
             
         
       
     
     in which
 R 1  is hydrogen; 
 R 1′  is hydrogen, methyl or fluorine; 
 R 2  is hydrogen; 
 R 3  is hydrogen, amino, methyl, methoxy, ethoxy, methylamino or dimethylamino; 
 R 4  is methyl; 
 n is 2; 
 two substituents R 5  together with the carbon atoms to which they are attached form a dioxine ring fused to the B ring; 
 R 6  is C 3 -C 6  alkyl, C 4 -C 6  cycloalkyl or C 5 -C 6  cycloalkenyl; 
 m is the number 1; 
 A is phenyl, pyridyl, imidazolyl, thienyl, furanyl, oxadiazolyl, pyrazolyl, pyrazinyl, pyridazinyl, pyrimidinyl, quinolinyl or isoquinolinyl,
 it being possible for A to be substituted by 0, 1 or 2 substituents R A , the substituents R A  being selected independently of one another from the group consisting of halogen, alkyl, cyano, trifluoromethyl, phenyl and alkoxy, 
 
 or 
 two substituents R A  together with the carbon atoms to which they are attached form a dioxolane ring fused to the A ring; 
 B is phenyl, naphthyl, pyridyl, thienyl, furanyl, quinolinyl or isoquinolinyl. 
 
   
   
       23 . A compound as claimed in  claim 22 , characterized in that
 R 1  is hydrogen;   R 1′  is hydrogen;   R 2  is hydrogen;   R 3  is hydrogen, amino, methylamino or dimethylamino;   R 4  is methyl;   n is 2;   two substituents R 5  together with the phenyl ring to which they are attached form a 1,3-benzodioxole or a 1,4-benzodioxane;   R 6  is isopropyl, tert-butyl, isobutyl, isopentyl, cyclobutyl or cyclopentyl;   m is the number 1;   A is phenyl, pyridyl, thienyl, quinolinyl or isoquinolinyl,
 it being possible for A to be substituted by 0, 1 or 2 substituents R A , the substituents R A  being selected independently of one another from the group consisting of fluorine, chlorine, C 1 -C 3  alkyl, cyano, trifluoromethyl, phenyl and C 1 -C 3  alkoxy, 
   or   two substituents R A  together with the phenyl ring to which they are attached form a 1,3-benzodioxole or a 1,4-benzodioxane;   B is phenyl, naphthyl, thienyl, quinolinyl or isoquinolinyl.   
   
   
       24 . A compound as claimed in one of  claims 1  or  21 , characterized in that R 1  is hydrogen. 
   
   
       25 . A compound as claimed in  claim 1 , characterized in that R 1′  is hydrogen. 
   
   
       26 . A compound as claimed in  claim 1 , characterized in that R 2  is hydrogen. 
   
   
       27 . A compound as claimed in  claim 1 , characterized in that R 4  is methyl. 
   
   
       28 . A compound as claimed in  claim 1 , characterized in that m is the number 1. 
   
   
       29 . A compound as claimed in  claim 1 , characterized in that R 3  is hydrogen or amino. 
   
   
       32 . A compound as claimed in  claim 1 , characterized in that R 6  is isopropyl, tert-butyl, isobutyl, isopentyl or cyclopentyl. 
   
   
       33 . A compound as claimed in  claim 1 , characterized in that A is phenyl or pyridyl, it being possible for A to be substituted by 0, 1 or 2 substituents R A , the substituents R A  being selected independently of one another from the group consisting of fluorine, chlorine, cyano, trifluoromethyl, phenyl and methoxy. 
   
   
       34 . A process for preparing compounds as claimed in  claim 1 , characterized in that
 by process [A]   a compound of the formula   
     
       
         
         
             
             
         
       
       in which R 2  to R 6 , B and n are as defined in  claim 1 , 
       is reacted with a compound of the formula 
     
     
       
         
         
             
             
         
       
       in which R 1  and R 1′ , A and m are as defined in  claim 1 , 
       it being possible for these to be in activated form if desired, 
       or 
       by process [B] 
       a compound of the formula 
     
     
       
         
         
             
             
         
       
       in which R 3 , R 4  and R 6  are as defined in  claim 1   
       is reacted with a compound of the formula 
     
     
       
         
         
             
             
         
       
       in which R 1 , R 1′ , R 2 , R 5 , A, B, m and n are as defined in  claim 1 , 
       it being possible for these to be in activated form if desired. 
     
   
   
       35 . A pharmaceutical composition comprising at least one compound as claimed in  claim 1  in combination with at least one pharmaceutically acceptable carrier or excipient. 
   
   
       36 . A method of treating a bacterial infection in a person or animal comprising administering to said person or animal an antibacterially effective amount of at least one compound of  claim 1 .