Compounds of use in the treatment of epilepsy, seizure, and electroconvulsive disorders

Abstract

The present invention provides pharmaceutical preparations and the uses thereof for preventing and/or treating seizures and other electroconvulsive disorders by administering a pharmaceutically effective amount of a therapeutic compound having the following formula (I): Embodiments include administering an effective amount of 4,4′-thiodianiline, 4,4′-diaminobenzophenone, 4,4′-methylenedianiline, 4,4′-diaminodiphenyl ether, or (3-aminophenyl)-(4-aminophenyl) amine, an analog, or a pharmaceutically accepted salt or complex thereof to a mammal in need of treatment or prevention of epilepsy, seizure, or other electroconvulsive disorder.

What is claimed is:  
     
         1 . A therapeutic compound, including resolved enantiomers, diastereoisomers, tautomers, salts, solvates and polymorphic forms thereof, having the following formula (I):  
       
         
           
           
               
               
           
         
       
       wherein 
 R 1 , R 2 , R 3 , and R 4 , are each independently selected from the group consisting of hydrogen, hydroxy, amino, phenyl, a substituted or unsubstituted C 1-10  alkyl, C 3-10  branched alkyl, a substituted or unsubstituted C 3-8  cycloalkyl, a substituted or unsubstituted arylalkyl, a substituted or unsubstituted C 1-10  alkoxyl and a substituted or unsubstituted C 1-10  acyl; and  
 X is selected from the group consisting of —O—, —S—, —N(H)—, —Se—, —Si—, —CH═CH—, —C≡C—, —N═N—, —N═CH—, —CH═N—, —C(S)—, —N(H)S(O)—, —N(H)SO 2 —, —N(H)O—, —N(H)S—, —S(O)—, —SO 2 —, —PO 4 —, —Si(O)—, —C(O)—, —CH 2 —, —CF 2 —, and a covalent bond.  
 
     
     
         2 . The compound of  claim 1 , wherein the substituted or unsubstituted arylalkyl comprises Ar—(CH 2 ) n ; where Ar is an aromatic ring and n is from 1 to 10.  
     
     
         3 . The compound of  claim 2 , wherein the substituents of the substituted groups are selected from the group consisting of halogen, phenyl, thio, amino, hydroxyl, hydroxylamino, nitrile, carboxyl, amido, phosphate, sulfate, sulfonamide, nitroso, nitrone, azido, imino, hydrazine, guanidino, oxyguanidino, methylguanidino, hydroxyguanidino, aminoguanidino, thioguanidino, amidino, oxyamidino, ureido, thioureido, thioamido and nitro.  
     
     
         4 . The compound of  claim 1 , wherein the compound is selected form the group consisting of 4,4′-thiodianiline, 4,4′-diaminobenzophenone, 4,4′-diaminodiphenyl ether, 4,4′-methylenedianiline, and (3-aminophenyl)-(4-aminophenyl) amine.  
     
     
         5 . The compound of  claim 1 , wherein the compound is 4,4′-thiodianiline.  
     
     
         6 . The compound of  claim 1 , wherein the compound is 4,4′-diaminobenzophenone.  
     
     
         7 . The compound of  claim 1 , wherein the compound is 4,4′-diaminodiphenyl ether.  
     
     
         8 . The compound of  claim 1 , wherein the compound is 4,4′-methylenedianiline.  
     
     
         9 . The compound of  claim 1 , wherein the compound is (3-aminophenyl)-(4-aminophenyl) amine.  
     
     
         10 . A pharmaceutical composition comprising the compound of  claim 1  in an admixture with a pharmaceutically acceptable carrier, adjuvant or vehicle.  
     
     
         11 . A pharmaceutical composition comprising the compound of  claim 3  in an admixture with a pharmaceutically acceptable carrier, adjuvant or vehicle.  
     
     
         12 . A pharmaceutical composition comprising the compound of  claim 4  in an admixture with a pharmaceutically acceptable carrier, adjuvant or vehicle.  
     
     
         13 . A pharmaceutical composition comprising the compound of  claim 5  in an admixture with a pharmaceutically acceptable carrier, adjuvant or vehicle.  
     
     
         14 . A pharmaceutical composition comprising the compound of  claim 6  in an admixture with a pharmaceutically acceptable carrier, adjuvant or vehicle.  
     
     
         15 . A pharmaceutical composition comprising the compound of  claim 7  in an admixture with a pharmaceutically acceptable carrier, adjuvant or vehicle.  
     
     
         16 . A pharmaceutical composition comprising the compound of  claim 8  in an admixture with a pharmaceutically acceptable carrier, adjuvant or vehicle.  
     
     
         17 . A pharmaceutical composition comprising the compound of  claim 9  in an admixture with a pharmaceutically acceptable carrier, adjuvant or vehicle.  
     
     
         18 . A method of treating, ameliorating, or preventing epilepsy, seizure or electroconvulsive disorders in mammals which comprises administering a therapeutic effective amount of the compound of  claim 1  to said mammal.  
     
     
         19 . A method of treating, ameliorating, or preventing epilepsy, seizure or electroconvulsive disorders in mammals which comprises administering a therapeutic effective amount of the compound of  claim 1  to said mammal.  
     
     
         20 . A method of treating, ameliorating, or preventing epilepsy, seizure or electroconvulsive disorders in mammals which comprises administering a therapeutic effective amount of the compound of  claim 3  to said mammal.  
     
     
         21 . A method of treating, ameliorating, or preventing epilepsy, seizure or electroconvulsive disorders in mammals which comprises administering a therapeutic effective amount of the compound of  claim 4  to said mammal.  
     
     
         22 . A method of treating, ameliorating, or preventing epilepsy, seizure or electroconvulsive disorders in mammals which comprises administering a therapeutic effective amount of the compound of  claim 5  to said mammal.  
     
     
         23 . A method of treating, ameliorating, or preventing epilepsy, seizure or electroconvulsive disorders in mammals which comprises administering a therapeutic effective amount of the compound of  claim 6  to said mammal.  
     
     
         24 . A method of treating, ameliorating, or preventing epilepsy, seizure or electroconvulsive disorders in mammals which comprises administering a therapeutic effective amount of the compound of  claim 7  to said mammal.  
     
     
         25 . A method of treating, ameliorating, or preventing epilepsy, seizure or electroconvulsive disorders in mammals which comprises administering a therapeutic effective amount of the compound of  claim 8  to said mammal.  
     
     
         26 . A method of treating, ameliorating, or preventing epilepsy, seizure or electroconvulsive disorders in mammals which comprises administering a therapeutic effective amount of the compound of  claim 9  to said mammal.  
     
     
         27 . The method of  claim 21 , wherein the therapeutic effective amount is from about 0.1 mg/kg to about 300 mg/kg.  
     
     
         28 . The method of  claim 21 , wherein the therapeutic effective amount is from about 1 mg/kg to about 40 mg/kg.