Polymorphic Forms of 2-(5-Bromo-4-(4-Cyclopropylnaphthalen-1-yl)-4H-1,2,4-Triazol-3-ylthio)Acetic Acid and Uses Thereof

Abstract

Crystalline polymorph forms of 2-(5-bromo-4-(4-cyclopropyl naphthalen-1-yl)-4H-1,2,4-triazol-3-ylthio)acetic acid are described. Pharmaceutical compositions and the uses of such compounds, compound forms, and compositions for the treatment of a variety of diseases and conditions are also presented.

What is claimed is: 
     
         1 . A method for treating or preventing gout, comprising administering an effective amount of a crystalline polymorph of 2-(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazol-3-ylthio)acetic acid: 
       
         
           
           
               
               
           
         
         characterized by peaks at 10.46, 18.76, and 19.83°2θ±0.1°2θ. 
       
     
     
         2 . The method of  claim 1 , wherein the crystalline polymorph is further characterized by at least one further peak at 18.21 or 23.08°2θ±0.1°2θ. 
     
     
         3 . The method of  claim 1 , wherein the crystalline polymorph exhibits an x-ray powder diffraction pattern substantially the same as the x-ray powder diffraction pattern shown in  FIG. 5 . 
     
     
         4 . The method of  claim 1 , wherein the crystalline polymorph is prepared by a method comprising the step of crystallizing 2-(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazol-3-ylthio)acetic acid from a mixture of water and ethyl acetate. 
     
     
         5 . The method of  claim 1 , further comprising administering allopurinol. 
     
     
         6 . The method of  claim 1 , further comprising administering febuxostat. 
     
     
         7 . A method for treating hyperuricemia, comprising administering an effective amount of a crystalline polymorph of 2-(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazol-3-ylthio)acetic acid: 
       
         
           
           
               
               
           
         
         characterized by peaks at 10.46, 18.76, and 19.83°2θ±0.1θ2θ. 
       
     
     
         8 . The method of  claim 7 , wherein the crystalline polymorph is further characterized by at least one further peak at 18.21 or 23.08°2θ±0.1°2θ. 
     
     
         9 . The method of  claim 7 , wherein the crystalline polymorph exhibits an x-ray powder diffraction pattern substantially the same as the x-ray powder diffraction pattern shown in  FIG. 5 . 
     
     
         10 . The method of  claim 7 , wherein the crystalline polymorph is prepared by a method comprising the step of crystallizing 2-(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazol-3-ylthio)acetic acid from a mixture of water and ethyl acetate. 
     
     
         11 . The method of  claim 7 , further comprising administering allopurinol. 
     
     
         12 . The method of  claim 7 , further comprising administering febuxostat. 
     
     
         13 . A method for treating or preventing a disease caused by elevated uric acid levels, comprising administering an effective amount of a crystalline polymorph of 2-(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazol-3-ylthio)acetic acid: 
       
         
           
           
               
               
           
         
         characterized by peaks at 10.46, 18.76, and 19.83°2θ±0.1°2θ. 
       
     
     
         14 . The method of  claim 13 , wherein the crystalline polymorph is further characterized by at least one further peak at 18.21 or 23.08°2θ±0.1°2θ. 
     
     
         15 . The method of  claim 13 , wherein the crystalline polymorph exhibits an x-ray powder diffraction pattern substantially the same as the x-ray powder diffraction pattern shown in  FIG. 5 . 
     
     
         16 . The method of  claim 13 , wherein the crystalline polymorph is prepared by a method comprising the step of crystallizing 2-(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazol-3-ylthio)acetic acid from a mixture of water and ethyl acetate. 
     
     
         17 . The method of  claim 13 , further comprising administering allopurinol. 
     
     
         18 . The method of  claim 13 , further comprising administering febuxostat. 
     
     
         19 . The method of  claim 13 , wherein the disease caused by elevated uric acid levels is gout in a patient with hyperuricemia. 
     
     
         20 . A method of treating hyperuricemia, treating or preventing gout, or a treating or preventing a disease caused by elevated uric acid levels, comprising administering an effective amount of a crystalline polymorph of 2-(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazol-3-ylthio)acetic acid: 
       
         
           
           
               
               
           
         
         characterized by peaks at 10.32, 18.84 and 20.75°2θ±0.1°2θ. 
       
     
     
         21 . The method of  claim 20 , wherein the crystalline polymorph is further characterized by at least two further peaks at 6.80, 21.54, 24.97, 25.53, 27.28 or 27.60°2θ±0.1°2θ. 
     
     
         22 . The method of  claim 20 , wherein the crystalline polymorph exhibits an x-ray powder diffraction pattern substantially the same as the x-ray powder diffraction pattern shown in  FIG. 1 . 
     
     
         23 . The method of  claim 20 , wherein the crystalline polymorphic form of 2-(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazol-3-ylthio)acetic acid is prepared by a method comprising the step of crystallizing 2-(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazol-3-ylthio)acetic acid from a mixture of water and acetic acid. 
     
     
         24 . The method of  claim 20 , further comprising administering allopurinol. 
     
     
         25 . The method of  claim 20 , further comprising administering febuxostat. 
     
     
         26 . The method of  claim 20 , wherein the disease caused by elevated uric acid levels is gout in a patient with hyperuricemia.