Methods of treating alpha adrenergic mediated conditions

Abstract

Described herein are compounds for and methods of treating conditions or diseases in a subject by administering to the subject a pharmaceutical composition containing an effective amount of an α-adrenergic modulator. The compounds and methods are also useful for alleviating types of pain, both acute and chronic.

1 . A method of treating a condition or disease which is neuropathic pain in a mammal comprising:
 administering a compound having a structure   
       
         
           
           
               
               
           
         
         wherein R 1  and R 2  are each independently selected from hydrogen, C 1-4  alkyl, C 1-4  alkoxy, OH, halogen, NR′ 2 , CN, CO 2 R′, C(O)NR′R″, alcohol, C 1-4  halogenated alkyl, C 1-4  halogenated alkoxy, and substituted or unsubstituted aryl or heteroaryl;
 R′ is selected from hydrogen, C 1-4  alkyl and C 1-4  halogenated alkyl, substituted or unsubstituted aryl or heteroaryl; 
 R″ is selected from hydrogen and C 1-4  alkyl, substituted or unsubstituted aryl or heteroaryl; and 
 
         wherein said compound activates at least one of said α-adrenergic receptors. 
       
     
     
         2 . The method according to  claim 1  wherein the neuropathic pain is selected from the group consisting of PHN (post-herpetic neuralgia), PTN (post-traumatic neuropathy), CRPS (complex regional pain syndrome) and drug-induced neuropathy. 
     
     
         3 . The method according to  claim 1  wherein R1 and R2 are each independently a halogen or halogenated alkyl. 
     
     
         4 . The method according to  claim 1  wherein said compound is N-(2-chloro-3-fluoro-benzyl)-4,5-dihydro-1H-imidazol-2-amine. 
     
     
         5 . The method according to  claim 1  wherein said compound is N-(2-difluoromethoxy)-benzyl)-4,5-dihydro-1H-imidazol-2-amine. 
     
     
         6 . The method according to  claim 1  wherein said compound is N-(2,3-dimethyl-benzyl)-4,5-dihydro-1H-imidazol-2-amine. 
     
     
         7 . The method according to  claim 1  wherein said compound is N-(trifluoromethyl-benzyl)-4,5-dihydro-1H-imidazol-2-amine. 
     
     
         8 . The method according to  claim 1  wherein said compound is N-(trifluoromethoxy-benzyl)-4,5-dihydro-1H-imidazol-2-amine. 
     
     
         9 . The method according to  claim 1  wherein said compound is N-(2-fluoro-benzyl)-4,5-dihydro-1H-imidazol-2-amine. 
     
     
         10 . The method according to  claim 1  wherein said compound is N-(2-fluoro-3-trifluoromethyl-benzyl)-4,5-dihydro-1H-imidazol-2-amine. 
     
     
         11 . The method according to  claim 1  wherein said compound is N-(2,3-dimethoxy-benzyl)-4,5-dihydro-1H-imidazol-2-amine. 
     
     
         12 . The method according to  claim 1  wherein said compound is N-(3-bromo-2-methoxy-benzyl)-4,5-dihydro-1H-imidazol-2-amine. 
     
     
         13 . The method according to  claim 1  wherein said compound is N-(2-chloro-benzyl)-4,5-dihydro-1H-imidazol-2-amine. 
     
     
         14 . The method according to  claim 1  wherein said compound is N-(2-methyl-benzyl)-4,5-dihydro-1H-imidazol-2-amine. 
     
     
         15 . The method according to  claim 1  wherein said compound is N-(3-chloro-2-fluoro-benzyl)-4,5-dihydro-1H-imidazol-2-amine. 
     
     
         16 . The method according to  claim 1  wherein said compound is N-(2,3-dichlorobenzyl)-4,5-dihydro-1H-imidazol-2-amine. 
     
     
         17 . The method according to  claim 1  wherein said compound is N-(2,3-dimethylbenzyl)-4,5-dihydro-1H-imidazol-2-amine. 
     
     
         18 . The method according to  claim 1  wherein said compound is N-(2-fluorobenzyl)-4,5-dihydro-1H-imidazol-2-amine. 
     
     
         19 . A pharmaceutical composition for treating a condition or disease which is neuropathic pain comprising:
 a compound having a structure   
       
         
           
           
               
               
           
         
         wherein R 1  and R 2  are each independently selected from hydrogen, C 1-4  alkyl, C 1-4  alkoxy, OH, halogen, NR′ 2 , CN, CO 2 R′, C(O)NR′R″, alcohol, C 1-4  halogenated alkyl, C 1-4  halogenated alkoxy, and substituted or unsubstituted aryl or heteroaryl;
 R′ is selected from hydrogen, C 1-4  alkyl and C 1-4  halogenated alkyl, substituted or unsubstituted aryl or heteroaryl; 
 R″ is selected from hydrogen and C 1-4  alkyl, substituted or unsubstituted aryl or heteroaryl; and 
 
         wherein said compound activates at least one of said α-adrenergic receptors. 
       
     
     
         20 . The composition according to  claim 19  wherein said condition or disease is selected from the group consisting of postherpetic neuralgia (PHN), post-traumatic neuropathy pain (PTN), complex regional pain syndrome (CRPS) and drug-induced neuropathy. 
     
     
         21 . The method of  claim 1  wherein the mammal is a human.