Compounds, compositions, and methods for treating diseases

Abstract

The present application is directed, in part, to compounds, and/or pharmaceutically acceptable salts or solvates thereof, and/or pharmaceutical compositions thereof, for modulating the activity of Sigmal receptor. The present application is further directed, in part, to methods for treating and/or preventing cancer using compounds disclosed herein, and/or pharmaceutically acceptable salts or solvates thereof, and/or pharmaceutical compositions thereof.

1 - 9 . (canceled) 
     
     
         10 . A method of treating or ameliorating cancer in a mammal, the method comprising administering to the mammal a therapeutically effective amount of a compound of Formula (I), or a pharmaceutically acceptable salt or solvate thereof: 
       
         
           
           
               
               
           
         
         wherein:
 R 1  is selected from the group consisting of H, halo, and haloalkyl; and 
 R 2  is pyrimidinyl. 
 
       
     
     
         11 . The method of  claim 10 , wherein the cancer is at least one selected from the group consisting of lung cancer, prostate cancer, liver cancer, pancreas cancer, CNS tumors, breast cancer, neuroblastoma, and leukemia. 
     
     
         12 . The method of  claim 10 , wherein the mammal is a mammal in need thereof. 
     
     
         13 . The method of  claim 10 , wherein the mammal is a human. 
     
     
         14 . A method of treating or ameliorating pain, the method comprising administering to the mammal a therapeutically effective amount of a compound of Formula (I), or a pharmaceutically acceptable salt or solvate thereof: 
       
         
           
           
               
               
           
         
         wherein:
 R 1  is selected from the group consisting of H, halo, and haloalkyl; and 
 R 2  is pyrimidinyl. 
 
       
     
     
         15 . The method of  claim 14 , wherein the mammal is a mammal in need thereof. 
     
     
         16 . The method of  claim 14 , wherein the mammal is a human. 
     
     
         17 . A method of treating or ameliorating a neurological disease, the method comprising administering to the mammal a therapeutically effective amount of a compound of Formula (I), or a pharmaceutically acceptable salt or solvate thereof: 
       
         
           
           
               
               
           
         
         wherein:
 R 1  is selected from the group consisting of H, halo, and haloalkyl; and 
 R 2  is pyrimidinyl. 
 
       
     
     
         18 . The method of  claim 17 , wherein the mammal is a mammal in need thereof. 
     
     
         19 . The method of  claim 17 , wherein the mammal is a human. 
     
     
         20 . The method of  claim 10 , wherein at least one of the following is true:
 i) the haloalkyl is C 1 -C 6  haloalkyl;   ii) R 1  is fluoro substituted C 1 -C 6  alkyl;   iii) R 1  is selected from the group consisting of —CF 3 , —C 2 F 5 , —CH 2 F, —CHF 2 , —CCl 3 , —CHCl 2 , and —CH 2 CF 3 ;   iv) the compound is selected from the group consisting of:   
       
         
           
           
               
               
           
         
         v) R 2  is selected from the group consisting of 
       
       
         
           
           
               
               
           
         
         vi) the compound is 
       
       
         
           
           
               
               
           
         
       
       or
 vii) the compound is administered as a pharmaceutical composition further comprising at least one additional therapeutic agent that inhibits the ubiquitin proteasome system (UPS) or autophagic survival pathway. 
 
     
     
         21 . The method of  claim 14 , wherein at least one of the following is true:
 i) the haloalkyl is C 1 -C 6  haloalkyl;   ii) R 1  is fluoro substituted C 1 -C 6  alkyl;   iii) R 1  is selected from the group consisting of —CF 3 , —C 2 F 5 , —CH 2 F, —CHF 2 , —CCl 3 , —CHCl 2 , and —CH 2 CF 3 ;   iv) the compound is selected from the group consisting of:   
       
         
           
           
               
               
           
         
         v) R 2  is selected from the group consisting of 
       
       
         
           
           
               
               
           
         
         vi) the compound is 
       
       
         
           
           
               
               
           
         
       
       or
 vii) the compound is administered as a pharmaceutical composition further comprising at least one additional therapeutic agent that inhibits the ubiquitin proteasome system (UPS) or autophagic survival pathway. 
 
     
     
         22 . The method of  claim 17 , wherein at least one of the following is true:
 i) the haloalkyl is C 1 -C 6  haloalkyl;   ii) R 1  is fluoro substituted C 1 -C 6  alkyl;   iii) R 1  is selected from the group consisting of —CF 3 , —C 2 F 5 , —CH 2 F, —CHF 2 , —CCl 3 , —CHCl 2 , and —CH 2 CF 3 ;   iv) the compound is selected from the group consisting of:   
       
         
           
           
               
               
           
         
         v) R 2  is selected from the group consisting of 
       
       
         
           
           
               
               
           
         
         vi) the compound is 
       
       
         
           
           
               
               
           
         
       
       or
 vii) the compound is administered as a pharmaceutical composition further comprising at least one additional therapeutic agent that inhibits the ubiquitin proteasome system (UPS) or autophagic survival pathway.