Novel salts and pharmaceutical compositions thereof for the treatment of inflammatory disorders

Abstract

The present invention discloses salts of a Compound 1: useful in the prophylaxis and/or treatment of inflammatory conditions, autoimmune diseases, proliferative diseases, allergy, transplant rejection, diseases involving degradation and/or disruption of cartilage homeostasis, congenital cartilage malformations, and/or diseases associated with hypersecretion of IL6 or interferons.

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         16 . A pharmaceutically acceptable salt of a compound according to Formula (I): 
       
         
           
           
               
               
           
         
         wherein the salt is a 1:1 free base/maleic acid salt. 
       
     
     
         17 . A pharmaceutically acceptable salt according to  claim 16 , wherein the salt is in a crystalline form. 
     
     
         18 . A pharmaceutically acceptable salt according to  claim 16 , wherein the salt exhibits peaks on a XRFD spectrum. 
     
     
         19 . A method for the prophylaxis and/or treatment of a condition selected from inflammatory conditions, autoimmune diseases, proliferative diseases, allergy, transplant rejection, diseases involving degradation and/or disruption of cartilage homeostasis, congenital cartilage malformations, and/or diseases associated with hypersecretion of IL6 or interferons, comprising administering an effective amount of a pharmaceutically acceptable salt according to  claim 16 . 
     
     
         20 . The method according to  claim 19 , wherein the pharmaceutically acceptable salt is administered in combination with another therapeutic agent. 
     
     
         21 . The method according to  claim 19 , wherein the further therapeutic agent is an agent for the prophylaxis and/or treatment of inflammatory conditions, autoimmune diseases, proliferative diseases, allergy, transplant rejection, diseases involving degradation and/or disruption of cartilage homeostasis, congenital cartilage malformations, and/or diseases associated with hypersecretion of IL6 or interferons. 
     
     
         22 . A method for preparing a pharmaceutically acceptable salt of  claim 16  comprising: combining the compound according to Formula I with maleic acid in an inert solvent; and precipitating said salt from said solvent. 
     
     
         23 . A method for preparing a pharmaceutically acceptable salt of  claim 16  comprising: combining the compound of Formula I and maleic acid in a suitable solvent in order to achieve full dissolution; evaporating the solvent in order to achieve supersaturation; and crystallizing the salt. 
     
     
         24 . The method according to  claim 22 , wherein the salt is obtained by mixing the compound of Formula I and the acid in a molar ratio of between 5:1 and 1:5 of Formula I: acid. 
     
     
         25 . The method according to  claim 22 , wherein the solvent is selected from acetonitrile, dioxane, THF, acetone, DCM, and MeOH. 
     
     
         26 . The pharmaceutically acceptable salt according to  claim 16 , obtainable by:
 i) suspending 1 equivalent of the compound of Formula I in 20 volumes of 5% water in acetone at 25° C.,   ii) warming the suspension of step i) to 50° C.,   iii) adding 2.1 equivalent of maleic acid (1 M solution in THF) to the stirred suspension at 50° C. obtained in the previous step ii),   iv) cooling the mixture of step iii) to 25° C. at 1° C./min and stirring at 25° C. for 22 h,   v) separating by filtration the resulting solid obtained in the previous step iv),   vi) drying under suction said resulting solid obtained in the previous step v).