Solid forms comprising (1e, 4e)-2-amino-n,n-dipropyl-8-(4-(pyrrolidine-1-carbonyl)phenyl)-3h-benzo[b]azepine-4-carboxamide, compositions thereof, and uses thereof

Abstract

Provided herein are compositions including the crystalline forms of (1E, 4E)-2-amino-N,N-dipropyl-8-(4-(pyrrolidine-1-carbonyl)phenyl)-3H-benzo[b] azepine-4-carboxamide (“Compound A”), methods of making the crystalline forms, and methods of using the crystalline forms for the treatment of diseases, including, for example, cancer.

1 . A crystalline form of the compound of formula (I): 
       
         
           
           
               
               
           
         
       
     
     
         2 . The crystalline form of the compound of  claim 1 , wherein said crystalline form comprises an unsolvated crystalline form. 
     
     
         3 - 88 . (canceled) 
     
     
         89 . The crystalline form of the compound of formula (I) of  claim 2 , wherein said crystalline form is characterized by an X-ray powder diffraction pattern comprising angle 2 θ peaks at about 11.9±0.2, 16.4±0.2, 18.5±0.2, 20.9±0.2, 21.2±0.2, 21.6±0.2, 23.0±0.2, 23.5±0.2, 24.2±0.2, and 27.4±0.2,
 wherein said x-ray powder diffraction spectrum is obtained using a Cu Kα radiation source (1.54 Å). 
 
     
     
         90 . The crystalline form of the compound of formula (I) of  claim 89 , characterized by an endothermic event with an onset temperature of about 199° C. and about 211° C. as measured by differential scanning calorimetry. 
     
     
         91 . The crystalline form of the compound of formula (I) of  claim 2 , wherein said crystalline form is characterized by an X-ray powder diffraction pattern comprising angle 2 θ peaks at about 11.0±0.2, 14.9±0.2, 18.0±0.2, 19.1±0.2, 21.0±0.2, and 22.8±0.2,
 wherein said x-ray powder diffraction spectrum is obtained using a Cu Kα radiation source (1.54 Å). 
 
     
     
         92 . The crystalline form of the compound of formula (I) of  claim 91 , characterized by an endothermic event with an onset temperature of about 211° C. as determined by differential scanning calorimetry. 
     
     
         93 . The crystalline form of the compound of formula (I) of  claim 2 , wherein said crystalline form is characterized by an X-ray powder diffraction pattern comprising angle 2 θ peaks at about 12.0±0.2, 13.4±0.2, 15.7±0.2, 16.4±0.2, 18.4±0.2, 19.5±0.2, 21.5±0.2, 22.4±0.2, 22.8±0.2, 23.5±0.2, and 24.2±0.2,
 wherein said x-ray powder diffraction spectrum is obtained using a Cu Kα radiation source (1.54 Å). 
 
     
     
         94 . The crystalline form of the compound of formula (I) of  claim 93 , characterized by an endothermic event with an onset temperature of about 206° C. as determined by differential scanning calorimetry. 
     
     
         95 . The crystalline form of the compound of formula (I) of  claim 2 , wherein said crystalline form is characterized by an X-ray powder diffraction pattern comprising angle 2 θ peaks at about 11.0±0.2, 15.3±0.2, 15.6±0.2, 17.5±0.2, 18.9±0.2, 20.0±0.2, 21.1±0.2, 22.1±0.2, 24.6±0.2, 25.1±0.2, and 26.5±0.2,
 wherein said x-ray powder diffraction spectrum is obtained using a Cu Kα radiation source (1.54 Å). 
 
     
     
         96 . The crystalline form of the compound of  claim 1 , wherein said crystalline form comprises a solvated crystalline form. 
     
     
         97 . The crystalline form of the compound of  claim 96 , wherein said solvated crystalline form is selected from the group consisting of 1,4-dioxane solvate, dichloromethane solvate, chlorobenzene solvate, and trifluoroethanol solvate. 
     
     
         98 . The 1,4-dioxane solvate of  claim 97 , wherein said crystalline form is characterized by an X-ray powder diffraction pattern comprising angle 2 θ peaks at about 10.7±0.2, 15.2±0.2, 15.5±0.2, 17.5±0.2, 18.6±0.2, 19.7±0.2, 20.9±0.2, 21.8±0.2, 24.2±0.2, 24.7±0.2, and 26.4±0.2,
 wherein said x-ray powder diffraction spectrum is obtained using a Cu Kα radiation source (1.54 Å). 
 
     
     
         99 . The 1,4-dioxane solvate of  claim 98 , characterized by an endothermic event with an onset temperature of about 94° C. and about 193° C. as determined by differential scanning calorimetry. 
     
     
         100 . The dichloromethane solvate of  claim 97 , wherein said crystalline form is characterized by an X-ray powder diffraction pattern comprising angle 2 θ peaks at about 15.6±0.2, 22.0±0.2, and 23.7±0.2,
 wherein said x-ray powder diffraction spectrum is obtained using a Cu Kα radiation source (1.54 Å). 
 
     
     
         101 . The dichloromethane solvate of  claim 100 , characterized by an endothermic event with an onset temperature of about 205° C. as determined by differential scanning calorimetry. 
     
     
         102 . The chlorobenzene solvate of  claim 97 , wherein said crystalline form is characterized by an X-ray powder diffraction pattern comprising angle 2 θ peaks at about 8.8±0.2, 17.7±0.2, and 21.4±0.2,
 wherein said x-ray powder diffraction spectrum is obtained using a Cu Kα radiation source (1.54 Å). 
 
     
     
         103 . The trifluoroethanol solvate of  claim 97 , wherein said crystalline form is characterized by an X-ray powder diffraction pattern comprising angle 2 θ peaks at about 4.6±0.2, 4.8±0.2, 15.3±0.2, 16.6±0.2, 18.1±0.2, and 22.9±0.2,
 wherein said x-ray powder diffraction spectrum is obtained using a Cu Kα radiation source (1.54 Å). 
 
     
     
         104 . The trifluoroethanol solvate of  claim 103 , characterized by an endothermic event with an onset temperature of about 206° C. as determined by differential scanning calorimetry. 
     
     
         105 . The trifluoroethanol solvate of  claim 97 , wherein said crystalline form is characterized by an X-ray powder diffraction pattern comprising angle 2 θ peaks at about 12.3±0.2, 14.8±0.2, 16.4±0.2, 18.5±0.2, 19.3±0.2, 19.6±0.2, 20.3±0.2, 21.1±0.2, 22.1±0.2, 22.5±0.2, 23.2±0.2, 24.1±0.2, 25.4±0.2, and 28.2±0.2,
 wherein said x-ray powder diffraction spectrum is obtained using a Cu Kα radiation source (1.54 Å). 
 
     
     
         106 . The trifluoroethanol solvate of  claim 105 , characterized by an endothermic event with an onset temperature of about 110° C. as determined by differential scanning calorimetry. 
     
     
         107 . A pharmaceutical composition comprising a crystalline form of the compound of formula (I) of  claim 1  and a pharmaceutically acceptable excipient. 
     
     
         108 . A method of agonizing Toll-like receptor 8 (TLR8), said method comprising contacting TLR8 with an effective amount of a crystalline form of the compound formula (I) of  claim 1 , wherein said effective amount agonizes said TLR8. 
     
     
         109 . A method of treating cancer, said method comprising administering a therapeutically effective amount of a crystalline form of the compound formula (I) of  claim 1 , to a subject in need thereof, thereby treating said cancer.