Heterocyclically substituted benzoylguanidines, process for their preparation, their use as medicaments or diagnostics, and medicaments comprising them

Abstract

Heterocyclically substituted benzoylguanidines of the formula I in which the substituents R(1) to R(4) have the meanings indicated in the claims. These compounds I are suitable as antiarrhythmic pharmaceuticals having a cardioprotective component for infarct prophylaxis and infarct treatment, and also for the treatment of angina pectoris. They also preventively inhibit the pathophysiological processes in the formation of ischemically induced damage, in particular in the elicitation of ischemically induced cardiac arrhythmias.

We claim:  
     
         1 . A heterocyclically substituted benzoylguanidine of the formula I  
       
         
           
           
               
               
           
         
       
       in which: 
 R(1) is —(CF 2 ) c —CF 3 ; 
 c is zero, 1, 2 or 3;  
 
 R(2) is (C 1 -C 9 )-heteroaryl, linked via C or N, which is unsubstituted or substituted by 1-3 substituents selected from the group consisting of F, Cl, CF 3 , CH 3 , methoxy, hydroxyl, amino, methylamino and dimethylamino;  
 R(3) is H, F, Cl, Br, I, CN, NO 2  or (C 1 -C 8 )-alkyl;  
 R(4) is H, (C 1 -C 4 )-alkyl, (C 1 -C 4 )-alkoxy, F, Cl, Br, I, CN or —(CF 2 ) o —CF 3 ; 
 o is zero, 1 or 2;  
 or a pharmaceutically tolerable salt thereof.  
 
 
     
     
         2 . A compound of  claim 1 , wherein: 
 R(1) is trifluoromethyl;    R(2) is imidazolyl or benzimidazolyl, linked via C or N, each of which is unsubstituted or substituted by 1-3 substituents selected from the group consisting of F, Cl, CF 3 , CH 3 , methoxy, hydroxyl, amino, methylamino and dimethylamino;    R(3) is H, F, Cl or (C 1 -C 4 )-alkyl;    R(4) is H, (C 1 -C 4 )-alkyl, (C 1 -C 4 )-alkoxy, F, Cl or CF 3 .    
     
     
         3 . A compound of  claim 1 , wherein: 
 R(1) is trifluoromethyl;    R(2) is imidazolyl or benzimidazolyl, linked via N, each of which is unsubstituted or substituted by 1-3 substituents selected from the group consisting of F, Cl, CF 3 , CH 3  and methoxy;    R(3) is H;    R(4) is H, methyl, methoxy, Cl or CF 3 .    
     
     
         4 . A process for preparing a compound I of  claim 1 , which comprises reacting a compound of the formula II  
       
         
           
           
               
               
           
         
       
       in which R(1) to R(4) have the meaning indicated and L is an easily nucleophilically substitutable leaving group, with guanidine.  
     
     
         5 . A method of treating or preventing an illness caused by an ischemic condition, comprising administering an effective amount of a compound of  claim 1  to a host in need of such treatment or prevention.  
     
     
         6 . A method of treating or preventing cardiac infarct, comprising administering an effective amount of a compound of  claim 1  to a host in need of such treatment or prevention.  
     
     
         7 . A method of treating or preventing angina pectoris, comprising administering an effective amount of a compound of  claim 1  to a host in need of such treatment or prevention.  
     
     
         8 . A method for the treatment or prevention of an ischemic condition of the heart, comprising administering an effective amount of a compound of  claim 1  to a host in need of each treatment or prevention.  
     
     
         9 . A method for the treatment or prevention of stroke or of an ischemic condition of the peripheral or central nervous system, which comprises administering an effective amount of a compound of  claim 1  to a host in need of such treatment or prevention.  
     
     
         10 . A method for the treatment or prevention of an ischemic condition of the peripheral organs or limbs, comprising administering an effective amount of a compound of  claim 1  to a host need of such treatment or prevention.  
     
     
         11 . A method of treating or preventing a state of shock, comprising administering an effective amount of a compound of  claim 1  to a host in need of such treatment or prevention.  
     
     
         12 . A method of protecting a transplant organ during surgical operation or organ transplantations, comprising administering an effective amount of a compound of  claim 1  to a host in need of such treatment.  
     
     
         13 . A method of preserving or protecting organ transplants for surgical measures, comprising bringing an effective amount of a compound of  claim 1  into contact with the organ transplant.  
     
     
         14 . A method of treating an illness in which cell proliferation is a primary or secondary cause, comprising administering an effective amount of a compound of  claim 1  to a host in need of such treatment.  
     
     
         15 . A method of treating or protecting a disorder of fat metabolism, comprising administering an effective amount of a compound of  claim 1  to a host in need of such treatment or protection.  
     
     
         16 . A pharmaceutical composition, comprising a compound of  claim 1  and a pharmaceutically acceptable carrier.