US2023116686A1PendingUtilityA1

Therapeutic compounds and uses thereof

Assignee: KALA PHARMACEUTICALS INCPriority: Feb 20, 2013Filed: May 18, 2022Published: Apr 13, 2023
Est. expiryFeb 20, 2033(~6.6 yrs left)· nominal 20-yr term from priority
C07D 519/00C07D 403/12A61K 9/08C07D 491/107A61P 3/00A61K 47/26A61P 27/02A61K 9/146A61K 31/517A61P 37/02A61P 17/02A61P 35/00C07D 471/04A61P 9/10A61P 27/06A61P 43/00A61K 9/0048A61P 29/00
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Claims

Abstract

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

Claims

exact text as granted — not AI-modified
1 . A method of treating an ocular disease in an eye of a subject in need thereof, comprising injecting a compound to the eye, wherein the compound is: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, wherein: 
         R 1  is H or optionally substituted C 1-6  alkyl; 
         R 2  is optionally substituted bicyclic heterocyclyl having 1 or 2 heteroatoms; 
         X is a bond, —O—, or —C(═O)—; 
         Y is CH; 
         R 3  is optionally substituted heteroaryl; and 
         n is 0, 1, 2, 3, or 4. 
       
     
     
         2 . The method of  claim 1 , wherein the ocular disease is a growth factor-associated disorder. 
     
     
         3 . The method of  claim 2 , wherein the growth factor is vascular endothelial growth factor. 
     
     
         4 . (canceled) 
     
     
         5 . (canceled) 
     
     
         6 . (canceled) 
     
     
         7 . The method of  claim 1 , wherein R 1  is CH 3 . 
     
     
         8 . The method of  claim 1 , wherein R 2  is 
       
         
           
           
               
               
           
         
         wherein p, q, s, and t are independently 0, 1, 2, 3, or 4. 
       
     
     
         9 . The method of  claim 1 , wherein X is a bond or —C(═O)—. 
     
     
         10 . (canceled) 
     
     
         11 . The method of  claim 1 , wherein n is 1 or 2 
     
     
         12 . (canceled) 
     
     
         13 . The method of  claim 1 , wherein the compound is: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, 
         wherein: 
         each instance of R 4  is independently H, optionally substituted C 1-6  alkyl, F, Cl, Br, I, CN, OH, or alkoxy; 
         R 5  is H or a nitrogen protecting group; and 
         m is 0, 1, 2, 3, 4, or 5. 
       
     
     
         14 . The method of  claim 13 , wherein at least one instance of R 4  is CH 3 , F, or H. 
     
     
         15 . (canceled) 
     
     
         16 . (canceled) 
     
     
         17 . (canceled) 
     
     
         18 . The method of  claim 1 , wherein R 2  is 
       
         
           
           
               
               
           
         
       
     
     
         19 . (canceled) 
     
     
         20 . (canceled) 
     
     
         21 . The method of  claim 1 , wherein the compound is: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         22 . A method of inhibiting growth factor signaling in a cell, comprising contacting the cell with an effective amount of a compound, wherein the compound is: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, wherein: 
         R 1  is H or optionally substituted C 1-6  alkyl; 
         R 2  is optionally substituted bicyclic heterocyclyl having 1 or 2 heteroatoms; 
         X is a bond, —O—, or —C(═O)—; 
         Y is CH; 
         R 3  is optionally substituted heteroaryl; and 
         n is 0, 1, 2, 3, or 4. 
       
     
     
         23 . (canceled) 
     
     
         24 . (canceled) 
     
     
         25 . (canceled) 
     
     
         26 . The method of  claim 22 , wherein R 1  is CH 3 . 
     
     
         27 . The method of  claim 22 , wherein R 2  is 
       
         
           
           
               
               
           
         
         wherein p, q, s, and t are independently 0, 1, 2, 3, or 4. 
       
     
     
         28 . The method of  claim 22 , wherein X is a bond or —C(═O)—. 
     
     
         29 . (canceled) 
     
     
         30 . The method of  claim 22 , wherein n is 1 or 2. 
     
     
         31 . (canceled) 
     
     
         32 . The method of  claim 22 , wherein the compound is: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, 
         wherein: 
         R 1  is H or optionally substituted C 1-6  alkyl; 
         R 2  is optionally substituted bicyclic heterocyclyl having 1 or 2 heteroatoms; 
         X is a bond, —O—, or —C(═O)—; 
         each instance of R 4  is independently H, optionally substituted C 1-6  alkyl, F, Cl, Br, I, CN, OH, or alkoxy; 
         R 5  is H or a nitrogen protecting group; 
         m is 0, 1, 2, 3, 4, or 5; and 
         n is 0, 1, 2, 3, or 4. 
       
     
     
         33 . The method of  claim 32 , wherein at least one instance of R 4  is CH 3 , F, or H. 
     
     
         34 . (canceled) 
     
     
         35 . (canceled) 
     
     
         36 . (canceled) 
     
     
         37 . The method of  claim 22 , wherein R 2  is 
       
         
           
           
               
               
           
         
       
     
     
         38 . (canceled) 
     
     
         39 . (canceled) 
     
     
         40 . The method of  claim 22 , wherein the compound is: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         41 .- 63 . (canceled)

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