Treatment of Neurodegenerative Diseases

Abstract

The present specification discloses beta-amino alcohols and methods of treating a neurodegenerative disease using such compounds.

1 . A method of treating a neurodegenerative condition, the method comprising the step of administering to an individual in need thereof a compound of formula (I) 
       
         
           
           
               
               
           
         
       
       wherein
 R 1  is CHR 4 —OR 5  or CHR 4 —SR 5 , or aryl or heteroaryl optionally substituted with one or more groups R 6 ; 
 R 2  is alkyl or is part of a ring with R 3 ; 
 R 3  is H, alkyl or CH 2  (when forming part of a ring with R 2 ); 
 R 4  is H or alkyl or is part of a ring with R 5 ; 
 R 5  is aryl or heteroaryl optionally substituted with R 7 ; 
 each R 6  is independently alkyl, CF 3 , OH, Oalkyl, OCOalkyl, CONH 2 , CN, halogen, NH 2 , NO 2 , NHCHO, NHCONH 2 , NHSO 2 alkyl, CONH 2 , SOMe, SO 2 NH 2 , Salkyl, CH 2 SO 2 alkyl or OCONalkyl 2 ; 
 R 7  is R 8  or (CH 2 ) n OR 8 , R 9 , CF 3 , OH, OR 9 , OCOR 9 , COR 9 , COOR 9 , CONH 2 , CH 2 CONH 2 , CN, halogen, NH 2 , NO 2 , NHCHO, NHCONH 2 , NHCONHR 7 , NHCON(R 9 ) 2 , NHCOR 9 , NHCOaryl, NHSO 2 Me, CONH 2 , SMe, SOMe or SO 2 NH 2 ; 
 R 8  is (CH 2 ) n OR 9 , (CH) n OR 9 , (CH 2 ) n COOR 9  or (CH 2 ) n COaryl; 
 R 9  is alkyl or cycloalkyl; and 
 n is 1 to 4; 
 or a salt thereof. 
 
     
     
         2 . The method according to  claim 1 , wherein the neurodegenerative condition is a multiple sclerosis. 
     
     
         3 . The method according to  claim 1 , wherein the neurodegenerative condition is an Alzheimer's disease. 
     
     
         4 . The method according to  claim 1 , wherein the neurodegenerative condition is a Parkinson's disease. 
     
     
         5 . The method according to  claim 1 , wherein the compound is chiral and is an enantiomer or a diastereomer. 
     
     
         6 . The method according to  claim 1 , wherein the compound has relatively little or no activity at an α adrenoceptor or a β adrenoceptor. 
     
     
         7 . The method according to  claim 1 , wherein the individual is also administered an additional therapeutic agent, the additional therapeutic agent includes a cholinesterase inhibitor, a steroid, an interferon, or a glutamate receptor agent. 
     
     
         8 . The method according to  claim 7 , wherein the glutamate receptor agent is an AMPA, a kappa agonist, or a NMDA agonist. 
     
     
         9 . The method according to  claim 7 , wherein the compound and the additional therapeutic agent are provided in combination. 
     
     
         10 . The method according to  claim 1 , wherein R 1  is aryl substituted by CF or halogen, R 2  is alkyl, and R 3  is H or alkyl. 
     
     
         11 . The method of  claim 1 , wherein the compound is (+)-erythro-2-tertbutylamino-1-(3-chlorophenyl)-propan-1-ol.