Deuterated derivatives of ruxolitinib

Abstract

The present invention in one embodiment provides a compound of Formula A: or a pharmaceutically acceptable salt thereof; pharmaceutical compositions comprising the compound; and methods of treating the indications disclosed herein.

1 . A compound represented by the following structural formula 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, wherein each position in the compound designated specifically as deuterium has at least 97% incorporation of deuterium. 
       
     
     
         2 . (canceled) 
     
     
         3 . A pharmaceutical composition comprising the compound of  claim 1 , and a pharmaceutically acceptable carrier. 
     
     
         4 . (canceled) 
     
     
         5 . The composition of  claim 3  further comprising a therapeutic agent selected from lenalidomide, panobinostat, capecitabine, exemestane and combinations thereof. 
     
     
         6 . A method of inhibiting the activity of one or more of JAK1 or JAK2, in a cell, comprising contacting such a cell with a compound of  claim 1 , or a pharmaceutically acceptable salt thereof. 
     
     
         7 . A method of treating myelofibrosis, pancreatic cancer, prostate cancer, breast cancer, leukemia, non-Hodgkin's lymphoma, multiple myeloma, psoriasis, or a combination thereof in a subject in need thereof, comprising administering to the subject a pharmaceutical composition of  claim 3 . 
     
     
         8 . The method of  claim 7 , wherein the myelofibrosis is primary myelofibrosis, post-polycythemia vera myelofibrosis, post-essential thrombocythemia myelofibrosis, essential thrombocythemia or a combination thereof. 
     
     
         9 . The method of  claim 7 , further comprising administering to the subject in need thereof, a therapeutic agent selected from lenalidomide, panobinostat, capecitabine, exemestane and combinations thereof. 
     
     
         10 . The compound of  claim 1 , wherein the pharmaceutically acceptable salt is the phosphate salt. 
     
     
         11 . The pharmaceutical composition of  claim 3 , wherein the pharmaceutically acceptable salt of the compound is the phosphate salt. 
     
     
         12 . The method of  claim 6 , wherein the pharmaceutically acceptable salt of the compound is the phosphate salt. 
     
     
         13 . The method of  claim 7 , wherein the pharmaceutically acceptable salt of the compound is the phosphate salt.