Therapeutic compounds and uses thereof

Abstract

The present invention relates to a compound formula (I): and to salts thereof, wherein R 1 , R 2 X, and Y have any of the values defined herein, and compositions and uses thereof. The compounds are useful as inhibitors of CBP and/or EP300. Also included are pharmaceutical compositions comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof, and methods of using such compounds and salts in the treatment of various CBP and/or EP300-mediated disorders.

We claim: 
     
         1 . A compound of formula (Ia): 
       
         
           
           
               
               
           
         
       
       or a salt thereof, wherein:
 R 1  is: C 1-12 alkyl, 
 
       
         
           
           
               
               
           
         
         R 2  is —C(O)—N(R e ) 2 , or —C(O)—R e ; 
         Y is selected from the group consisting of: 
       
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
       and
 each R e  is independently selected from hydrogen, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, and C 2-5 cycloalkyl, wherein each C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, and C 2-5 cycloalkyl is optionally substituted with one or more groups independently selected from oxo, halo, amino, hydroxyl, C 1-3 alkoxy, and C 1 -C 3  alkyl that is optionally substituted with one or more groups independently selected from halo. 
 
     
     
         2 . The compound or salt of  claim 1  wherein, R 1  is selected from the group consisting of: methyl, 
       
         
           
           
               
               
           
         
       
     
     
         3 . The compound or salt of any one of  claim 1 , wherein R 2  is C 1-4 alkanoyl. 
     
     
         4 . The compound or salt thereof of  claim 1  selected from the group consisting of: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
       or a salt thereof. 
     
     
         5 . A compound or salt thereof selected from the group consisting of: 
       
         
           
           
               
               
           
         
       
       or a salt thereof. 
     
     
         6 . A composition comprising a compound as described in  claim 1  or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable adjuvant, carrier, or vehicle. 
     
     
         7 . A method for treating a CBP and/or EP300-mediated cancer in an animal by selectively inhibiting a bromodomain of the CBP and/or EP300 in the animal, comprising administering an effective amount of a compound or a pharmaceutically acceptable salt thereof, as described in  claim 1 , to the animal, wherein the animal has a mutation in the CBP and/or EP300, and wherein the cancer is selected from lung cancer, breast cancer, pancreatic cancer, colorectal cancer, or melanoma. 
     
     
         8 . A composition comprising a compound as described in  claim 5  or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable adjuvant, carrier, or vehicle. 
     
     
         9 . A method for treating a CBP and/or EP300-mediated cancer in an animal by selectively inhibiting a bromodomain of the CBP and/or EP300 in the animal, comprising administering an effective amount of a compound or a pharmaceutically acceptable salt thereof, as described in  claim 5 , to the animal, wherein the animal has a mutation in the CBP and/or EP300, and wherein the cancer is selected from lung cancer, breast cancer, pancreatic cancer, colorectal cancer, or melanoma.