Prodrugs of 2,4-pyrimidinediamine compounds and their uses

Abstract

The present disclosure provides prodrugs of biologically active 2,4-pyrimidinediamine compounds, salts and hydrates of the prodrugs, compositions comprising the prodrugs, intermediates and methods for synthesizing the prodrugs and methods of using the prodrugs in a variety of applications.

The invention claimed is: 
     
       1. An oral dosage formulation comprising a hydrate of the prodrug salt: 
       
         
           
           
               
               
           
         
         orand a pharmaceutically-acceptable carrier, excipient, and/or diluent; wherein:
 M is Na;   the prodrug salt hydrate present in the oral dosage formulation is substantially crystalline prodrug salt hydrate; and the powder X-ray diffraction data of the crystalline prodrug salt hydrate comprises a characteristic peak at a two theta value of 9.9±0.1° in response to radiation of wavelength 1.54059 Å.   
       
     
     
       2. The oral dosage formulation of  claim 1 , the formulation comprising from about 50 mg to about 400 mg of the crystalline prodrug salt hydrate. 
     
     
       3. The oral dosage formulation of  claim 1 , wherein the powder X-ray diffraction data of the crystalline prodrug salt hydrate comprises a characteristic peak at a two theta value of 11.8±0.1°. 
     
     
       4. The oral dosage formulation of  claim 1 , wherein the powder X-ray diffraction data of the crystalline prodrug salt hydrate comprises a characteristic peak at a two theta value of 21.8±0.1°. 
     
     
       5. The oral dosage formulation of  claim 1 , wherein the powder X-ray diffraction data of the crystalline prodrug salt hydrate comprises a characteristic peak at a two theta value of 13.2°±0.1°. 
     
     
       6. The oral dosage formulation of  claim 1 , wherein the hydrate of the prodrug salt has the formula: 
       
         
           
           
               
               
           
         
         wherein x is from about 1 to about 15. 
       
     
     
       7. The oral dosage formulation of  claim 6 , wherein x is from about 5 to about 10. 
     
     
       8. The oral dosage formulation of  claim 6 , wherein x is from about 5 to about 8. 
     
     
       9. The oral dosage formulation of  claim 6 , wherein x is 6. 
     
     
       10. The oral dosage formulation of  claim 8 , wherein the powder X-ray diffraction data of the crystalline prodrug salt hydrate comprises a characteristic peak at a two theta value of 3.4°±0.1°. 
     
     
       11. The oral dosage formulation of  claim 1 , wherein the hydrate is: