US2004157889A1PendingUtilityA1

Method of treating of demyelinating diseases or conditions

Assignee: AVENTIS PHARMA INCPriority: Feb 15, 2001Filed: Feb 3, 2004Published: Aug 12, 2004
Est. expiryFeb 15, 2021(expired)· nominal 20-yr term from priority
A61P 9/00A61P 43/00A61P 37/00A61P 9/10A61P 35/00A61P 25/00A61P 27/02A61P 3/00A61P 25/04A61P 25/02A61P 29/00A61P 25/28A61P 19/02A61P 19/00A61P 17/02A61P 19/08A61P 13/10A61P 13/02A61P 13/00A61K 31/4439
58
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Claims

Abstract

N-(Pyridinyl)-1H-indol-1-amines of formula I provide a unique combination of blocking properties for both the potassium and sodium channels. These compounds are useful for the treatment of Demyelinating Diseases and Conditions such as Multiple Sclerosis, Spinal Cord Injury, Traumatic Brain Injury and Stroke. The compounds are also useful for Stroke Rehabilitation, the treatment of Bladder Irritation and Dysfunction, and the treatment of Neuropathic Pain and Chemokine-Induced Pain.

Claims

exact text as granted — not AI-modified
We claim:  
     
         1 . A method of treating Demyelinating Diseases said method comprising administering to a patient in need thereof a therapeutically effective amount of a compound of formula I  
       
         
           
           
               
               
           
         
       
       wherein 
 m is 0, 1 or 2;  
 n is 0, 1 or 2;  
 p is 0 or 1;  
 each R is independently hydrogen, halogen, trifluoromethyl, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, benzyloxy, hydroxy, nitro or amino;  
 each R 1  is independently hydrogen, C 1 -C 6 alkyl, C 1 -C 6 alkenyl, C 1 -C 6 alkanoyl, halogen, cyano, —C(O)C 1 -C 6 alkyl, —C 1 -C 6 alkyleneCN, —C 1 -C 6 alkyleneNR′R″ wherein R′ and R″ are each independently hydrogen or C 1 -C 6 alkyl,  
 —C 1 -C 6 alkyleneOC(O)C 1 -C 6 alkyl, or —CH(OH)R 4 wherein R 4  is hydrogen or C 1 -C 6 alkyl;  
 R 2  is hydrogen, C 1 -C 6 alkyl optionally substituted with halogen, hydroxy or benzyloxy, C 1 -C 6 alkenyl, C 1 -C 6 alkynyl,  
 —CO 2 C 1 -C 6 alkyl, or —R 5 —NR′ R″ wherein R 5  is C 1 -C 6 alkylene, C 1 -C 6 alkenylene or C 1 -C 6 alkynylene and R′ and R″ are each independently hydrogen, C 1 -C 6 alkyl or alternatively the group —NR′R″ as a whole is 1-pyrrolidinyl; and  
 R 3  is hydrogen, nitro, amino, halogen, C 1 -C 6 alkoxy, hydroxy or C 1 -C 6 alkyl  
 or a pharmaceutically acceptable salt thereof.  
 
     
     
         2 . The method of  claim 1  wherein R is hydrogen, halogen, trifluoromethyl, or C 1 -C 6 alkyl; R 1  is hydrogen or C 1 -C 6 alkyl; R 2  is hydrogen or C 1 -C 6 alkyl; R 3  is hydrogen, C 1 -C 6 alkyl or halogen; and p is 0.  
     
     
         3 . The method of  claim 1  wherein the Demyelinating Disease is multiple sclerosis.  
     
     
         4 . The method of  claim 2  wherein the compound has the following formula  
       
         
           
           
               
               
           
         
       
     
     
         5 . The method of  claim 4  wherein the Demyelinating Disease is multiple sclerosis.  
     
     
         6 . A method of treating Demyelinating Conditions said method comprising administering to a patient in need thereof a therapeutically effective amount of the compound of  claim 1 .  
     
     
         7 . The method of  claim 6  wherein R is hydrogen, halogen, trifluoromethyl, or C 1 -C 6 alkyl; R 1  is hydrogen or C 1 -C 6 alkyl; R 2  is hydrogen or C 1 -C 6 alkyl; R 3  is hydrogen, C 1 -C 6 alkyl or halogen; and p is 0.  
     
     
         8 . The method of  claim 6  wherein the Demyelinating Condition is Spinal Cord Injury.  
     
     
         9 . The method of  claim 6  wherein the Demyelinating Condition is Traumatic Brain Injury.  
     
     
         10 . The method of  claim 6  wherein the Demyelinating Condition is Stroke.  
     
     
         11 . The method of  claim 7  wherein the compound has the following formula  
       
         
           
           
               
               
           
         
       
     
     
         12 . The method of  claim 11  wherein the Demyelinating Condition is Spinal Cord Injury.  
     
     
         13 . The method of  claim 11  wherein the Demyelinating Condition is Traumatic Brain Injury.  
     
     
         14 . The method of  claim 11  wherein the Demyelinating Condition is Stroke.  
     
     
         15 . A method of Stroke Rehabilitation said method comprising administering to a patient in need thereof a therapeutically effective amount of the compound of  claim 1 .  
     
     
         16 . The method of  claim 14  wherein R is hydrogen, halogen, trifluoromethyl, or C 1 -C 6 alkyl; R 1  is hydrogen or C 1 -C 6 alkyl; R 2  is hydrogen or C 1 -C 6 alkyl; R 3  is hydrogen, C 1 -C 6 alkyl or halogen; and p is 0.  
     
     
         17 . The method of  claim 16  wherein the compound has the following formula  
       
         
           
           
               
               
           
         
       
     
     
         18 . A method of blocking the potassium channel in a patient in need thereof by administering to a patient in need thereof a therapeutically effective amount of the compound of  claim 1 .  
     
     
         19 . The method of  claim 18  wherein R is hydrogen, halogen, trifluoromethyl, or C 1 -C 6 alkyl; R 1  is hydrogen or C 1 -C 6 alkyl; R 2  is hydrogen or C 1 -C 6 alkyl; R 3  is hydrogen, C 1 -C 6 alkyl or halogen; and p is 0.  
     
     
         20 . The method of  claim 19  wherein the compound has the following formula  
       
         
           
           
               
               
           
         
       
     
     
         21 . The method of  claim 2  wherein the compound has the following formula  
       
         
           
           
               
               
           
         
       
     
     
         22 . The method of  claim 7  wherein the compound has the following formula  
       
         
           
           
               
               
           
         
       
     
     
         23 . The method of  claim 22  wherein the demyelinating condition is Spinal Cord Injury.  
     
     
         24 . The method of  claim 22  wherein the demyelinating condition is Traumatic Brain Injury.  
     
     
         25 . The method of  claim 22  wherein the demyelinating condition is Stroke.  
     
     
         26 . A method of treating Neuropathic Pain said method comprising administering to a patient in need thereof a therapeutically effective amount of the compound of  claim 1 .  
     
     
         27 . The method of  claim 26  wherein the compound has the following formula:  
       
         
           
           
               
               
           
         
       
     
     
         28 . A method of treating Bladder Irritation said method comprising administering to a patient in need thereof a therapeutically effective amount of the compound of  claim 1 .  
     
     
         29 . The method of  claim 28  wherein the compound has the following formula:  
       
         
           
           
               
               
           
         
       
     
     
         30 . A method of treating Over Active Bladder said method comprising administering to a patient in need thereof a therapeutically effective amount of the compound of  claim 1 .  
     
     
         31 . The method of  claim 30  wherein the compound has the following formula:  
       
         
           
           
               
               
           
         
       
     
     
         32 . A method of treating chemokine-induced pain said method comprising administering to a patient in need thereof a therapeutically effective amount of the compound of  claim 1 .  
     
     
         33 . The method of  claim 32  wherein the compound has the following formula:

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