Benzoylguanidlne salt and hydrates thereof

Abstract

4-[4-(2-pyrrolylcarbonyl)-1-piperazinyl]-3-trifluoromethylbenzoylguanidine hydrochloride and its hydrates, processes for preparing this benzoylguanidine salt and its hydrates, pharmaceutical compositions containing this benzoylguanidine salt and its hydrates, and its use in treating diseases, particularly those in which inhibition of the cellular Na + /H + exchange is of therapeutic benefit.

1 . 4-[4-(2-pyrrolylcarbonyl)-1-piperazinyl]-3-trifluoromethylbenzoylguanidine hydrochloride 1  
       
         
           
           
               
               
           
         
       
     
     
         2 . A pharmaceutical composition comprising: 
 (a) the compound according to  claim 1;  and    (b) a pharmaceutically acceptable excipient.    
     
     
         3 . A method of treating diseases in which inhibition of the cellular Na + /H +  exchange is of therapeutic benefit in a patient in need thereof, the method comprising administering to the patient an effective amount of the compound according to  claim 1 .  
     
     
         4 . The method according to  claim 3 , wherein the compound according to  claim 1  is administered in the form of an aqueous injectable solution, a tablet, a suppository, an ointment, a transdermal plaster, an inhalation aerosol, or a nasal spray.  
     
     
         5 . A method of treating diseases in which inhibition of the cellular Na + /H +  exchange is of therapeutic benefit in a patient in need thereof, the method comprising administering to the patient an effective amount of a hydrate of 4-[4-(2-pyrrolylcarbonyl)-1-piperazinyl]-3-trifluoromethylbenzoylguanidine hydrochloride 1  
       
         
           
           
               
               
           
         
       
     
     
         6 . A method of treating diseases in which inhibition of the cellular Na + /H +  exchange is of therapeutic benefit in a patient in need thereof, the method comprising administering to the patient an effective amount of a monohydrate of 4-[4-(2-pyrrolylcarbonyl)-1-piperazinyl]-3-trifluoromethylbenzoylguanidine hydrochloride 1  
       
         
           
           
               
               
           
         
       
     
     
         7 . A method of treating diseases in which inhibition of the cellular Na + /H +  exchange is of therapeutic benefit in a patient in need thereof, the method comprising administering to the patient an effective amount of a hemihydrate of 4-[4-(2-pyrrolylcarbonyl)-1-piperazinyl]-3-trifluoromethylbenzoylguanidine hydrochloride 1 
       
         
           
           
               
               
           
         
       
     
     
         8 . The method according to  claim 5 , wherein the a hydrate of 4-[4-(2-pyrrolylcarbonyl)-1-piperazinyl]-3-trifluoromethylbenzoylguanidine hydrochloride 1 is administered in the form of an aqueous injectable solution, a tablet, a suppository, an ointment, a transdermal plaster, an inhalation aerosol, or a nasal spray.  
     
     
         9 . The method according to  claim 6 , wherein the monohydrate of 4-[4-(2-pyrrolylcarbonyl)-1-piperazinyl]-3-trifluoromethylbenzoylguanidine hydrochloride 1 is administered in the form of an aqueous injectable solution, a tablet, a suppository, an ointment, a transdermal plaster, an inhalation aerosol, or a nasal spray.  
     
     
         10 . The method according to  claim 7 , wherein the 4-[4-(2-pyrrolylcarbonyl)-1-piperazinyl]-3-trifluoromethylbenzoylguanidine hydrochloride 1 is administered in the form of an aqueous injectable solution, a tablet, a suppository, an ointment, a transdermal plaster, an inhalation aerosol, or a nasal spray.  
     
     
         11 . A method of treating a cardiovascular disease in a patient in need thereof, the method comprising administering to the patient an effective amount of the compound according to  claim 1 .  
     
     
         12 . The method according to  claim 11 , wherein the compound according to  claim 1  is administered in the form of an aqueous injectable solution, a tablet, a suppository, an ointment, a transdermal plaster, an inhalation aerosol, or a nasal spray.  
     
     
         13 . A method of treating a cardiovascular disease in a patient in need thereof, the method comprising administering to the patient an effective amount of a hydrate of 4-[4-(2-pyrrolylcarbonyl)-1-piperazinyl]-3-trifluoromethylbenzoylguanidine hydrochloride 1  
       
         
           
           
               
               
           
         
       
     
     
         14 . The method according to  claim 13 , wherein the a hydrate of 4-[4-(2-pyrrolylcarbonyl)-1-piperazinyl]-3-trifluoromethylbenzoylguanidine hydrochloride 1 is administered in the form of an aqueous injectable solution, a tablet, a suppository, an ointment, a transdermal plaster, an inhalation aerosol, or a nasal spray.  
     
     
         15 . A method of treating a cardiovascular disease in a patient in need thereof, the method comprising administering to the patient an effective amount of a monohydrate of 4-[4-(2-pyrrolylcarbonyl)-1-piperazinyl]-3-trifluoromethylbenzoylguanidine hydrochloride 1 
       
         
           
           
               
               
           
         
       
     
     
         16 . The method according to  claim 15 , wherein the monohydrate of 4-[4-(2-pyrrolylcarbonyl)-1-piperazinyl]-3-trifluoromethylbenzoylguanidine hydrochloride 1 is administered in the form of an aqueous injectable solution, a tablet, a suppository, an ointment, a transdermal plaster, an inhalation aerosol, or a nasal spray.  
     
     
         17 . A method of treating a cardiovascular disease in a patient in need thereof, the method comprising administering to the patient an effective amount of a hemihydrate of 4-[4-(2-pyrrolylcarbonyl)-1-piperazinyl]-3-trifluoromethylbenzoylguanidine hydrochloride 1  
       
         
           
           
               
               
           
         
       
     
     
         18 . The method according to  claim 17 , wherein the 4-[4-(2-pyrrolylcarbonyl)-1-piperazinyl]-3-trifluoromethylbenzoylguanidine hydrochloride 1 is administered in the form of an aqueous injectable solution, a tablet, a suppository, an ointment, a transdermal plaster, an inhalation aerosol, or a nasal spray.  
     
     
         19 . A method of treating coronary heart disease, cardiac infarct, angina pectoris, stable angina pectoris, ventricular arrhythmia, subventricular arrhythmias, cardiac insufficiency, embolism in the pulmonary circulation, acute or chronic kidney failure, chronic renal insufficiency, cerebral infarct, reperfusion damage in the restoration of blood supply to areas of the brain after the dissolving of vascular occlusions, or acute or chronic circulatory disorders of the brain in a patient in need thereof, the method comprising administering to the patient an effective amount of the compound according to  claim 1 .  
     
     
         20 . The method according to  claim 12 , wherein the compound according to  claim 1  is administered in the form of an aqueous injectable solution, a tablet, a suppository, an ointment, a transdermal plaster, an inhalation aerosol, or a nasal spray.  
     
     
         21 . A method of treating coronary heart disease, cardiac infarct, angina pectoris, stable angina pectoris, ventricular arrhythmia, subventricular arrhythmias, cardiac insufficiency, embolism in the pulmonary circulation, acute or chronic kidney failure, chronic renal insufficiency, cerebral infarct, reperfusion damage in the restoration of blood supply to areas of the brain after the dissolving of vascular occlusions, or acute or chronic circulatory disorders of the brain in a patient in need thereof, the method comprising administering to the patient an effective amount of a hydrate of 4-[4-(2-pyrrolylcarbonyl)-1-piperazinyl]-3-trifluoromethylbenzoylguanidine hydrochloride 1 
       
         
           
           
               
               
           
         
       
     
     
         22 . The method according to  claim 21 , wherein the a hydrate of 4-[4-(2-pyrrolylcarbonyl)-1-piperazinyl]-3-trifluoromethylbenzoylguanidine hydrochloride 1 is administered in the form of an aqueous injectable solution, a tablet, a suppository, an ointment, a transdermal plaster, an inhalation aerosol, or a nasal spray.  
     
     
         23 . A method of treating coronary heart disease, cardiac infarct, angina pectoris, stable angina pectoris, ventricular arrhythmia, subventricular arrhythmias, cardiac insufficiency, embolism in the pulmonary circulation, acute or chronic kidney failure, chronic renal insufficiency, cerebral infarct, reperfusion damage in the restoration of blood supply to areas of the brain after the dissolving of vascular occlusions, or acute or chronic circulatory disorders of the brain in a patient in need thereof, the method comprising administering to the patient an effective amount of a monohydrate of 4-[4-(2-pyrrolylcarbonyl)-1-piperazinyl]-3-trifluoromethylbenzoylguanidine hydrochloride 1 
       
         
           
           
               
               
           
         
       
     
     
         24 . The method according to  claim 23 , wherein the monohydrate of 4-[4-(2-pyrrolylcarbonyl)-1-piperazinyl]-3-trifluoromethylbenzoylguanidine hydrochloride 1 is administered in the form of an aqueous injectable solution, a tablet, a suppository, an ointment, a transdermal plaster, an inhalation aerosol, or a nasal spray.  
     
     
         25 . A method of treating coronary heart disease, cardiac infarct, angina pectoris, stable angina pectoris, ventricular arrhythmia, subventricular arrhythmias, cardiac insufficiency, embolism in the pulmonary circulation, acute or chronic kidney failure, chronic renal insufficiency, cerebral infarct, reperfusion damage in the restoration of blood supply to areas of the brain after the dissolving of vascular occlusions, or acute or chronic circulatory disorders of the brain in a patient in need thereof, the method comprising administering to the patient an effective amount of a hemihydrate of 4-[4-(2-pyrrolylcarbonyl)-1-piperazinyl]-3-trifluoromethylbenzoylguanidine hydrochloride 1 
       
         
           
           
               
               
           
         
       
     
     
         26 . The method according to  claim 25 , wherein the 4-[4-(2-pyrrolylcarbonyl)-1-piperazinyl]-3-trifluoromethylbenzoylguanidine hydrochloride 1 is administered in the form of an aqueous injectable solution, a tablet, a suppository, an ointment, a transdermal plaster, an inhalation aerosol, or a nasal spray.