Compounds and methods for treating multiple sclerosis

Abstract

The invention described herein pertains to the treatment of multiple sclerosis. In particular, the invention described herein pertains to the treatment of multiple sclerosis using compounds that modulate the action of acrolein.

1 - 33 . (canceled) 
     
     
         34 . A composition comprising a fused hydrazinopyridazine in a therapeutically effective amount for treating a patient with multiple sclerosis, wherein the composition is formulated for sustained release of the fused hydrazinopyridazine. 
     
     
         35 . The composition according to  claim 34 , wherein the fused hydrazinopyridazine is a compound of the formula: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, wherein:
 R is independently selected in each instance from hydrogen, acyl, or sulfonyl; or alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heteroalkyl, heteroalkenyl, cycloheteroalkyl, cycloheteroalkenyl, aryl, heteroaryl, arylalkyl, or heteroarylalkyl, each of which is optionally substituted; and 
 R A  represents three substituents, each of which is independently selected from the group consisting of hydrogen, halo, hydroxy and derivatives thereof, amino and derivatives thereof, thio and derivatives thereof, acyl, carboxylate or a derivative thereof, hydroxylamino and derivatives thereof, hydrazino and derivatives thereof, sulfonyl or a derivative thereof, or sulfonyl or a derivative thereof; or alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heteroalkyl, heteroalkenyl, cycloheteroalkyl, cycloheteroalkenyl, aryl, heteroaryl, arylalkyl, or heteroarylalkyl, each of which is optionally substituted; and two of R A  are taken together with the attached carbons to form an optionally substituted saturated, unsaturated, or aromatic carbocycle or heterocycle. 
 
     
     
         36 . The composition according to  claim 35 , wherein R A  represents a hydrogen; or
 R A  includes an optionally substituted benzo group; or   R A  includes an optionally substituted fused piperidine; or   R A  includes a hydrazino or derivative thereof; or   R A  includes a hydrazino; or   R A  includes amino or a derivative thereof; or   R A  includes dialkylamino, where each alkyl is independently selected, and independently optionally substituted.   
     
     
         37 . The composition according to  claim 35 , wherein each R is hydrogen; or at least one R is acyl; or at least one R is optionally substituted alkoxycarbonyl. 
     
     
         38 . The composition according to  claim 37 , wherein each R is hydrogen. 
     
     
         39 . The composition according to  claim 37 , wherein at least one R is acyl. 
     
     
         40 . The composition according to  claim 37 , wherein at least one R is optionally substituted alkoxycarbonyl. 
     
     
         41 . The composition according to  claim 35 , wherein the fused hydrazinopyridazine is selected from the group consisting of hydralazine, dihydralazine, and endralazine. 
     
     
         42 . The composition according to  claim 34 , wherein the composition is formulated for oral administration. 
     
     
         43 . The composition according to  claim 42 , wherein the composition is formulated as a single unit dosage. 
     
     
         44 . The composition according to  claim 42 , wherein the composition is formulated as a divided unit dosage. 
     
     
         45 . A method for treating a patient with multiple sclerosis, the method comprising: providing a composition comprising a fused hydrazinopyridazine in a therapeutically effective amount for treating the patient with multiple sclerosis, wherein the composition is formulated for sustained release of the fused hydrazinopyridazine. 
     
     
         46 . The method according to  claim 45 , wherein the fused hydrazinopyridazine is a compound of the formula: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, wherein:
 R is independently selected in each instance from hydrogen, acyl, or sulfonyl; or alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heteroalkyl, heteroalkenyl, cycloheteroalkyl, cycloheteroalkenyl, aryl, heteroaryl, arylalkyl, or heteroarylalkyl, each of which is optionally substituted; and 
 R A  represents three substituents, each of which is independently selected from the group consisting of hydrogen, halo, hydroxy and derivatives thereof, amino and derivatives thereof, thio and derivatives thereof, acyl, carboxylate or a derivative thereof, hydroxylamino and derivatives thereof, hydrazino and derivatives thereof, sulfonyl or a derivative thereof, or sulfonyl or a derivative thereof; or alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heteroalkyl, heteroalkenyl, cycloheteroalkyl, cycloheteroalkenyl, aryl, heteroaryl, arylalkyl, or heteroarylalkyl, each of which is optionally substituted; and two of R A  are taken together with the attached carbons to form an optionally substituted saturated, unsaturated, or aromatic carbocycle or heterocycle. 
 
     
     
         47 . The method according to  claim 46 , wherein R A  represents a hydrogen; or
 R A  includes an optionally substituted benzo group; or   R A  includes an optionally substituted fused piperidine; or   R A  includes a hydrazino or derivative thereof; or   R A  includes a hydrazino; or   R A  includes amino or a derivative thereof; or   R A  includes dialkylamino, where each alkyl is independently selected, and independently optionally substituted.   
     
     
         48 . The method according to  claim 46 , wherein each R is hydrogen; or at least one R is acyl; or at least one R is optionally substituted alkoxycarbonyl. 
     
     
         49 . The method according to  claim 48 , wherein each R is hydrogen. 
     
     
         50 . The method according to  claim 48 , wherein at least one R is acyl. 
     
     
         51 . The method according to  claim 48 , wherein at least one R is optionally substituted alkoxycarbonyl. 
     
     
         52 . The method according to  claim 46 , wherein the fused hydrazinopyridazine is selected from the group consisting of hydralazine, dihydralazine, and endralazine. 
     
     
         53 . The method according to  claim 45 , wherein the composition is formulated for oral administration.