Fused tricyclic dual inhibitors of cdk 4/6 and flt3

Abstract

Compounds of Formula I are useful inhibitors of CDK 4, CDK6, and FLT3. Such compounds are useful in treating cancer and various other disease conditions. Compounds of Formula I have the following structure: where R 1 is a group of Formula IA, Formula IB, Formula IC, or Formula ID and the definitions of the other variables are provided herein.

1 - 43 . (canceled) 
     
     
         44 . A compound having a formula selected from the group consisting of 
       
         
           
           
               
               
           
         
       
       or a hydrochloride salt or hydrate thereof. 
     
     
         45 . A compound of  claim 44 , wherein the compound is 
       
         
           
           
               
               
           
         
       
     
     
         46 . A compound of  claim 44 , wherein the compound is 
       
         
           
           
               
               
           
         
       
     
     
         47 . A compound of  claim 44 , wherein the compound is 
       
         
           
           
               
               
           
         
       
     
     
         48 . A method of treating cancer, the method comprising:
 administering to a subject an effective amount of a compound selected from the group consisting of   
       
         
           
           
               
               
           
         
         or a hydrochloride salt or hydrate thereof. 
       
     
     
         49 . The method of  claim 48 , wherein the compound is 
       
         
           
           
               
               
           
         
       
       or the hydrochloride salt or the hydrate thereof. 
     
     
         50 . The method of  claim 48 , wherein the compound is 
       
         
           
           
               
               
           
         
       
       or the hydrochloride salt or the hydrate thereof. 
     
     
         51 . A method of treating cancer, the method comprising:
 administering to a subject an effective amount of a compound having the following formula   
       
         
           
           
               
               
           
         
         or the hydrochloride salt or the hydrate thereof. 
       
     
     
         52 . The method of  claim 51 , wherein the compound is in a hydrochloride salt form. 
     
     
         53 . The method of  claim 51 , wherein the cancer is selected from acute myeloid leukemia, acute lymphoblastic leukemia, myelodysplastic syndrome, multiple myeloma, chronic myeloid leukemia, acute lymphocytic leukemia, chronic lymphocytic leukemia, non-Hodgkin lymphoma, another lymphoma, another myeloma, or another leukemia. 
     
     
         54 . The method of  claim 53 , wherein the cancer is acute myeloid leukemia. 
     
     
         55 . The method of  claim 53 , wherein the cancer is Rb-positive. 
     
     
         56 . The method of  claim 48 , wherein the cancer is selected from acute myeloid leukemia, acute lymphoblastic leukemia, myelodysplastic syndrome, multiple myeloma, chronic myeloid leukemia, acute lymphocytic leukemia, chronic lymphocytic leukemia, non-Hodgkin lymphoma, another lymphoma, another myeloma, or another leukemia. 
     
     
         57 . A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of  claim 44 . 
     
     
         58 . A pharmaceutical composition of  claim 57 , wherein the compound is present as a hydrochloride salt. 
     
     
         59 . A pharmaceutical composition of  claim 57 , wherein the compound is 
       
         
           
           
               
               
           
         
       
     
     
         60 . A pharmaceutical composition of  claim 57 , wherein the compound is 
       
         
           
           
               
               
           
         
       
     
     
         61 . A pharmaceutical composition of  claim 57 , wherein the compound is