Aurora kinase and janus kinase inhibitors for prevention of graft versus host disease

Abstract

Disclosed herein are compounds and methods for reducing the risk of developing, preventing, or treating graft versus host disease (GVHD) in a subject. The compounds can concurrently block Aurora kinase A and JAK2 signal transduction which synergistically suppresses alloreactive human T-cells in vitro, prevents xenogeneic graft-versus-host disease without impairing anti-tumor responses, and promotes the development and suppressive potency of CD39+ inducible Treg. In certain aspects, disclosed are compounds of Formula I-V.

1 - 18 . (canceled) 
     
     
         19 . A compound comprising the formula IIIC: 
       
         
           
           
               
               
           
         
         wherein 
         R 1  is selected from the group consisting of H, Cl, F, Br, I, C 1 -C 6  alkyl, CN, NO 2 , and NH 2 ; 
         R 2  is selected from the group consisting of H, F, and Cl; and 
         each R 4  is selected, independently, from the group consisting of H, COOH, CONH 2 , CONR 5 , SO 2 NH 2 , CONSO 2 R 5 , tetrazole, 4-morpholine, and COR 5 ; 
         each R 5  is selected, independently, from the group consisting of C 1 -C 6  alkyl, cycloalkyl, heteroaryl, and heteroalkyl; and 
         m is 1-5, 
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         20 . The compound of  claim 19 , wherein m is 1 and R 4  is selected from the group consisting of COOH, 2-CONH 2 , 4-CONH 2 , SO 2 NH 2 , tetrazole, and 4-morpholine. 
     
     
         21 . The compound of  claim 19 , wherein R 1  is Cl, F, Br, or I and R 2  is H. 
     
     
         22 . The compound of  claim 19 , wherein the compound is: 
       
         
           
           
               
               
           
         
       
     
     
         23 - 24 . (canceled)