1-Amino-triazolo(1,5-A)pyridine-substituted Urea Derivative and Uses Thereof

Abstract

Provided herein is a compound, 1-(4-(3-amino-[1,2,3]triazolo[1,5-a]pyridin-4-yl)phenyl)-3-(3-chlorophenyl)urea, pharmaceutical compositions thereof, and crystal forms thereof. Also provided are particles (e.g., nanoparticles) comprising the compound, and pharmaceutical compositions thereof, that are mucus penetrating. Also provided herein are methods and kits for using the compound, and pharmaceutical compositions thereof, for treating and/or preventing diseases associated with abnormal or pathological angiogenesis and/or aberrant signaling of a growth factor (e.g., vascular endothelial growth factor (VEGF)), such as proliferative diseases (e.g., cancers, benign neoplasms, inflammatory diseases, autoimmune diseases) and ocular diseases (e.g., macular degeneration, glaucoma, diabetic retinopathy, retinoblastoma, edema, uveitis, dry eye, blepharitis, and post-surgical inflammation) in a subject in need thereof.

What is claimed is: 
     
         1 . A compound of Formula (I): 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt or prodrug thereof. 
       
     
     
         2 . A crystal form of 
       
         
           
           
               
               
           
         
         wherein the crystal form has an X-ray powder diffraction (XRPD) pattern with peaks at about 10.5, about 14.4, about 19.3, about 21.7, and about 24.7 degrees 2θ. 
       
     
     
         3 . A pharmaceutical composition comprising a compound of  claim 1 , or a pharmaceutically acceptable salt or prodrug thereof, or a crystal form of  claim 2 , and a pharmaceutically acceptable excipient or carrier. 
     
     
         4 . The pharmaceutical composition of  claim 3 , wherein the pharmaceutical composition is suitable for topical administration. 
     
     
         5 . The pharmaceutical composition of  claim 3 , wherein the pharmaceutical composition is suitable for injection. 
     
     
         6 . The pharmaceutical composition of  claim 3 , wherein the pharmaceutical composition is suitable for delivery to the eye. 
     
     
         7 . The pharmaceutical composition of  claim 3  or  5 , wherein the pharmaceutical composition is in a container configured to administer eye drops. 
     
     
         8 . The pharmaceutical composition of  claim 3 , wherein the pharmaceutical composition is suitable for oral administration. 
     
     
         9 . The pharmaceutical composition of  claim 3 , wherein the pharmaceutical composition is suitable for inhalation. 
     
     
         10 . A method of treating a disease comprising administering to a subject in need thereof a therapeutically effective amount of a compound of  claim 1 , the crystal form of  claim 2 , or the pharmaceutical composition of any one of  claims 3 - 9 . 
     
     
         11 . The method of  claim 10 , wherein the disease is a proliferative disease. 
     
     
         12 . The method of  claim 11 , wherein the disease is cancer. 
     
     
         13 . The method of  claim 10 , wherein the disease is an ocular disease. 
     
     
         14 . The method of  claim 13 , wherein the ocular disease is retinopathy. 
     
     
         15 . The method of  claim 13 , wherein the ocular disease is age-related macular degeneration (AMD). 
     
     
         16 . The method of  claim 13 , wherein the ocular disease is corneal neovascularization. 
     
     
         17 . The method of  claim 13 , wherein the ocular disease is an ocular neovascular disease. 
     
     
         18 . The method of  claim 13 , wherein the ocular disease is diabetic macular edema. 
     
     
         19 . The method of  claim 13 , wherein the ocular disease is cystoid macular edema. 
     
     
         20 . The method of  claim 13 , wherein the ocular disease is retinal vein occlusion. 
     
     
         21 . A method of inhibiting growth factor signaling comprising administering to a subject a therapeutically effective amount of a compound  claim 1 , the crystal form of  claim 2 , or a pharmaceutical composition of any one of  claims 3 - 9 . 
     
     
         22 . The method according to any one of  claims 10 - 21 , wherein the compound or the pharmaceutical composition is administered topically. 
     
     
         23 . The method according to any one of  claims 10 - 21 , wherein the compound or the pharmaceutical composition is administered by injection. 
     
     
         24 . The method according to any one of  claims 10 - 21 , wherein the compound or the pharmaceutical composition is administered to the eye. 
     
     
         25 . The method according to any one of  claims 10 - 21 , wherein the compound or the pharmaceutical composition is administered orally. 
     
     
         26 . The method according to any one of  claims 10 - 21 , wherein the compound or the pharmaceutical composition is administered by inhalation. 
     
     
         27 . A method of inhibiting growth factor signaling in a subject in need thereof comprising:
 administering to the subject a therapeutically effective amount of a compound  claim 1 , the crystal form of  claim 2 , or a pharmaceutical composition of any one of  claims 3 - 9 .