Inhibitors of mutant isocitrate dehydrogenases and compositions and methods thereof

Abstract

The invention provides novel chemical compounds useful for treating cancer, or a related disease or disorder thereof, and pharmaceutical composition and methods of preparation and use thereof.

1 - 48 . (canceled) 
     
     
         49 . A method for treating, reducing, or preventing a disease or disorder, comprising administering to a subject in need thereof a pharmaceutical composition comprising a compound having the structural formula of (I): 
       
         
           
           
               
               
           
         
       
       wherein,
 each of Ring A, Ring B and Ring C is independently a 5- or 6-membered cyclic or bicyclic alkyl, heteroalkyl, aryl, or heteroaryl ring; 
 each R W  is independently a hydrogen, a halide, OH, NH 2 , alkyl, alkyl amine, alkyl amide, alkoxy, or an electrophilic group R E ; 
 R 1  is H, halide, alkyl amine, methoxy, hydroxy or a C 1 -C 3  alkyl group; 
 X is CH 2 , NH, O, S or a single bond; 
 Y is CH 2 , NH, O or S; and 
 Z is CH 2 , NH, O or S, 
 
       or a pharmaceutically acceptable form thereof, effective to treat, prevent, or reduce one or more cancers, or a related disease or disorder thereof, in a mammal, including a human, and a pharmaceutically acceptable excipient, carrier, or diluent. 
     
     
         50 . The method of  claim 49 , wherein the compound has the structure of: 
       
         
           
           
               
               
           
         
       
     
     
         51 . The method of  claim 50 , wherein the one or more cancers are selected from B-acute lymphoblastic leukemias, B-acute lymphoblastic leukemias, chronic myelomonocytic leukemia, Acute myelogenous leukemia, lymphoma, myelodysplasia syndrome, myeloproliferative neoplasms and myeloproliferative neoplasms.