Inhibition of olig2 activity

Abstract

Described herein are compounds and pharmaceutical compositions containing such compounds, which inhibit the activity of Olig2. Also described herein are methods of using such Olig2 inhibitors, alone and in combination with other compounds, for treating cancer and other diseases. In particular the Olig2 inhibitors may be used to treat glioblastoma.

1 .- 13 . (canceled) 
     
     
         14 . A method for treating a disease in a subject comprising administering to the subject in need thereof a composition comprising a compound of Formula (IIA), or a pharmaceutically acceptable salt, solvate, or prodrug thereof, wherein the disease is cancer or Down's Syndrome, wherein the compound of Formula (IIA) is: 
       
         
           
           
               
               
           
         
         wherein: 
         each R 1  is independently halogen, —CN, —NO 2 , —OH, —OCF 3 , —OCH 2 F, —OCF 2 H, —SR 8 , —N(R 8 )S(═O) 2 R 9 , —S(═O) 2 N(R 8 ) 2 , —S(═O)R 9 , —S(═O) 2 R 9 , —C(═O)R 9 , —CO 2 R 8 , —N(R 8 ) 2 , —C(═O)N(R 8 ) 2 , —N(R 8 )C(═O)R 9 , substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted C 1 -C 6 alkoxy, substituted or unsubstituted C 1 -C 6 heteroalkyl, substituted or unsubstituted C 2 -C 7 heterocycloalkyl, substituted or unsubstituted C 3 -C 8 cycloalkyl, substituted or unsubstituted C 6 -C 10 aryl, or substituted or unsubstituted C 2 -C 7 heteroaryl; or two R 1  are taken together to form a substituted or unsubstituted heterocyclic ring or a substituted or unsubstituted carbocyclic ring: 
         R 2  and R 3  are each independently H, —CN, C 1 -C 4 alkyl, C 3 -C 6 cycloalkyl, or C 2 -C 7 heterocycloalkyl; 
         R 4  is H, halogen, —CN, —NO 2 , —OH, —OCF 3 , —OCH 2 F, —OCF 2 H, —SR 8 , —N(R 8 )S(═O) 2 R 9 , —S(═O) 2 N(R 8 ) 2 , —S(═O)R 9 , —S(═O) 2 R 9 , —C(═O)R 9 , —CO 2 R 8 , —N(R 8 ) 2 , —C(═O)N(R 8 ) 2 , —N(R 8 )C(═O)R 9 , substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted C 1 -C 6 alkoxy, substituted or unsubstituted C 1 -C 6 heteroalkyl, substituted or unsubstituted C 2 -C 7 heterocycloalkyl, substituted or unsubstituted C 3 -C 8 cycloalkyl, substituted or unsubstituted C 6 -C 10 aryl, or substituted or unsubstituted C 2 -C 7 heteroaryl: wherein when n is 0, R 4  is not halogen; 
         R 5  is halogen, —CN, —OH, —CF 3 , or substituted or unsubstituted C 1 -C 6 alkyl; 
         R 6  is —(C(R 14 )(R 15 )) m N(R 11 )(R 12 ): 
         R 11  and R 12  are each —CH 3 ; 
         R 13  is H, substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted C 2 -C 7 heterocycloalkyl, substituted or unsubstituted C 3 -C 8 cycloalkyl, substituted or unsubstituted —C 1 -C 4 alkylC 6 -C 10 aryl, or substituted or unsubstituted —C 1 -C 4 alkylC 2 -C 7 heteroaryl; 
         each R 14  and R 15  are each independently H, or substituted or unsubstituted C 1 -C 6 alkyl; or R 14  and R 15  are taken together to form a 4-, 5-, 6-membered cycloalkyl ring: 
         each R 8  is independently H, or substituted or unsubstituted C 1 -C 6 alkyl: 
         R 9  is substituted or unsubstituted C 1 -C 6 alkyl: 
         R 10  is H, or C 1 -C 4 alkyl: 
         m is 2-6; 
         n is 0-4: or 
       
       a pharmaceutically acceptable salt, solvate, or prodrug thereof. 
     
     
         15 . The method of  claim 14 , wherein the disease is cancer. 
     
     
         16 . The method of  claim 15 , wherein the cancer is brain cancer, glioblastoma multiforme, medulloblastoma, astrocytomas, brain stem gliomas, meningiomas, oligodendrogliomas, melanoma, lung cancer, breast cancer, or leukemia. 
     
     
         17 . The method of  claim 14 , wherein the disease is Down's Syndrome. 
     
     
         18 . A method for inhibiting the activity of Olig2 in a cell comprising contacting the cell with a compound of claim  1 , or a pharmaceutically acceptable salt, solvate, or prodrug thereof.