Therapeutic compounds and uses thereof

Abstract

Described herein are compounds of Formula (I) or Formula (VI), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Also provided are particles (e.g., nanoparticles) comprising compounds of Formula (I) or Formula (VI) and pharmaceutical compositions thereof that are mucus penetrating. Methods of using the compounds or pharmaceutical compositions thereof for treating diseases are also provided.

1 - 65 . (canceled) 
     
     
         66 . A method of treating an ocular disease, comprising administering to a subject in need thereof a compound having the formula: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, 
         wherein: 
         R 1  is hydrogen, substituted C 1-6  alkyl, or unsubstituted C 1-6  alkyl; 
         R 2  is hydrogen, substituted carbocyclyl, unsubstituted carbocyclyl, substituted heterocyclyl, unsubstituted heterocyclyl, substituted aryl, unsubstituted aryl, substituted heteroaryl, or unsubstituted heteroaryl; 
         X is a bond, —O—, —S—, —NR A1 —, —C(═O)—, branched substituted C 1-6  alkylene, unbranched substituted C 1-6  alkylene, branched unsubstituted C 1-6  alkylene, or unbranched unsubstituted C 1-6  alkylene; 
         R A1  is hydrogen, substituted acyl, unsubstituted acyl, substituted alkyl, unsubstituted alkyl, or a nitrogen protecting group; 
         Y is N or CH; 
         each occurrence of R 3  is, independently, hydrogen, halogen, substituted acyl, unsubstituted acyl, substituted alkyl, unsubstituted alkyl, substituted alkenyl, unsubstituted alkenyl, substituted alkynyl, unsubstituted alkynyl, substituted carbocyclyl, unsubstituted carbocyclyl, substituted heterocyclyl, unsubstituted heterocyclyl, substituted aryl, unsubstituted aryl, substituted heteroaryl, unsubstituted heteroaryl, —CN, —NO 2 , —OR D1a , —N(R D1a ) 2 , —SR D1a , —CH 2 OR D1a , —CH 2 N(R D1a ) 2 , —CH 2 SR D1a , —C(═O)R D1a , —C(═O)OR D1a , —C(═O)SR D1a , —C(═O)N(R D1a ) 2 , —C(═S)R D1a , —C(═S)OR D1a , —C(═S)SR D1a , —C(═S)N(R D1a ) 2 , —C(═NR D1a )R D1a , —C(═NR D1a )OR D1a , —C(═NR D1a )SR D1a , or C(═NR D1a )N(R D1a ) 2 ; 
         each occurrence of R D1a  is, independently, hydrogen, substituted alkyl, unsubstituted alkyl, substituted alkenyl, unsubstituted alkenyl, substituted alkynyl, unsubstituted alkynyl, substituted carbocyclyl, unsubstituted carbocyclyl, substituted heterocyclyl, unsubstituted heterocyclyl, substituted aryl, unsubstituted aryl, substituted heteroaryl, or unsubstituted heteroaryl, or two R D1a  groups are joined to form a substituted heterocyclic ring or an unsubstituted heterocyclic ring; 
         Z is substituted aliphatic, unsubstituted aliphatic, substituted heterocyclyl, unsubstituted heterocyclyl, substituted aryl, unsubstituted aryl, substituted heteroaryl, unsubstituted heteroaryl, substituted heterocyclylalkyl, unsubstituted heterocyclylalkyl, substituted arylalkyl, unsubstituted arylalkyl, substituted heteroaralkyl, unsubstituted heteroaralkyl, substituted quinolyl, or unsubstituted quinolyl; 
         m is 0, 1, 2, 3, or 4; and 
         n is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10. 
       
     
     
         67 . The method of  claim 66 , wherein:
 R 1  is hydrogen, substituted C 1-6  alkyl, or unsubstituted C 1-6  alkyl;   R 2  is heterocyclyl;   X is a bond, —O—, or —C(═O)—;   each occurrence of R 3  is, independently, hydrogen, F, Cl, Br, I, CN, or OH;   Y is CH or N;   Z is substituted aliphatic, unsubstituted aliphatic, substituted heterocyclylalkyl, unsubstituted heterocyclylalkyl, substituted aryl, unsubstituted aryl, substituted heteroaryl, unsubstituted heteroaryl, substituted quinolyl, or unsubstituted quinolyl;   m is 0, 1, 2, 3, or 4; and   n is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10.   
     
     
         68 . The method of  claim 66 , wherein:
 R 1  is hydrogen, substituted C 1-6  alkyl, or unsubstituted C 1-6  alkyl;   R 2  is heterocyclyl;   X is a bond, —O—, or —C(═O)—;   each occurrence of R 3  is, independently, hydrogen, F, Cl, Br, I, CN, or OH;   Y is CH;   Z is C 1-6  alkyl, substituted heterocyclylalkyl, unsubstituted heterocyclylalkyl, substituted aryl, unsubstituted aryl, substituted heteroaryl, unsubstituted heteroaryl, substituted quinolyl, or unsubstituted quinolyl;   m is 0, 1, 2, 3, or 4; and   n is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10.   
     
     
         69 . The method of  claim 66 , wherein R 2  is 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         70 . The method of  claim 66 , wherein R 2  is 
       
         
           
           
               
               
           
         
       
     
     
         71 . The method of  claim 66 , wherein the compound has a formula: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         72 . The method of  claim 66 , wherein the compound has a formula: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         73 . The method of  claim 66 , wherein the compound is administered as a pharmaceutical composition comprising a pharmaceutically acceptable carrier and the compound. 
     
     
         74 . The method of  claim 67 , wherein the compound is administered as a pharmaceutical composition comprising a pharmaceutically acceptable carrier and the compound. 
     
     
         75 . The method of  claim 68 , wherein the compound is administered as a pharmaceutical composition comprising a pharmaceutically acceptable carrier and the compound. 
     
     
         76 . The method of  claim 69 , wherein the compound is administered as a pharmaceutical composition comprising a pharmaceutically acceptable carrier and the compound. 
     
     
         77 . The method of  claim 70 , wherein the compound is administered as a pharmaceutical composition comprising a pharmaceutically acceptable carrier and the compound. 
     
     
         78 . The method of  claim 71 , wherein the compound is administered as a pharmaceutical composition comprising a pharmaceutically acceptable carrier and the compound. 
     
     
         79 . The method of  claim 72 , wherein the compound is administered as a pharmaceutical composition comprising a pharmaceutically acceptable carrier and the compound. 
     
     
         80 . The method of  claim 66 , wherein the ocular disease is a retinopathy, age-related macular degeneration, or glaucoma. 
     
     
         81 . The method of  claim 67 , wherein the ocular disease is a retinopathy, age-related macular degeneration, or glaucoma. 
     
     
         82 . The method of  claim 68 , wherein the ocular disease is a retinopathy, age-related macular degeneration, or glaucoma. 
     
     
         83 . The method of  claim 69 , wherein the ocular disease is a retinopathy, age-related macular degeneration, or glaucoma. 
     
     
         84 . The method of  claim 70 , wherein the ocular disease is a retinopathy, age-related macular degeneration, or glaucoma. 
     
     
         85 . The method of  claim 71 , wherein the ocular disease is a retinopathy, age-related macular degeneration, or glaucoma. 
     
     
         86 . The method of  claim 72 , wherein the ocular disease is a retinopathy, age-related macular degeneration, or glaucoma. 
     
     
         87 . The method of  claim 73 , wherein the ocular disease is a retinopathy, age-related macular degeneration, or glaucoma. 
     
     
         88 . The method of  claim 74 , wherein the ocular disease is a retinopathy, age-related macular degeneration, or glaucoma. 
     
     
         89 . The method of  claim 75 , wherein the ocular disease is a retinopathy, age-related macular degeneration, or glaucoma. 
     
     
         90 . The method of  claim 76 , wherein the ocular disease is a retinopathy, age-related macular degeneration, or glaucoma. 
     
     
         91 . The method of  claim 77 , wherein the ocular disease is a retinopathy, age-related macular degeneration, or glaucoma. 
     
     
         92 . The method of  claim 78 , wherein the ocular disease is a retinopathy, age-related macular degeneration, or glaucoma. 
     
     
         93 . The method of  claim 79 , wherein the ocular disease is a retinopathy, age-related macular degeneration, or glaucoma.