Highly active anti-neoplastic and anti-proliferative agents

Abstract

This invention is in the area of improved compounds and methods for treating selected cancers and hyperproliferative disorders.

We claim: 
     
         1 . A method of treating a leukemia of myelogenous origin in a human in need thereof comprising administering to the host an effective amount of a compound having the structure: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         2 . The method of  claim 1 , wherein the leukemia of myelogenous origin is acute myelogenous leukemia (AML). 
     
     
         3 . The method of  claim 2 , wherein the AML is undifferentiated AML. 
     
     
         4 . The method of  claim 2 , wherein the AML is myeloblastic leukemia with minimal cell maturation. 
     
     
         5 . The method of  claim 2 , wherein the AML is myeloblastic leukemia with cell maturation. 
     
     
         6 . The method of  claim 2 , wherein the AML is promyelocytic leukemia. 
     
     
         7 . The method of  claim 2 , wherein the AML is myelomonocytic leukemia. 
     
     
         8 . The method of  claim 2 , wherein the AML is myelomonocytic leukemia with eosinophilia. 
     
     
         9 . The method of  claim 2 , wherein the AML is monocytic leukemia. 
     
     
         10 . The method of  claim 2 , wherein the AML is erythroleukemia. 
     
     
         11 . The method of  claim 2 , wherein the AML is megakaryoblastic leukemia. 
     
     
         12 . The method of  claim 1 , wherein the leukemia of myelogenous origin is chronic myelogenous leukemia (CML). 
     
     
         13 . The method of  claim 1 , wherein the leukemia of myelogenous origin is juvenile myelomonocytic leukemia (JMML). 
     
     
         14 . The method of  claim 1 , wherein the leukemia of myelogenous origin is chronic myelomonocytic leukemia (CMML). 
     
     
         15 . The method of  claim 1 , wherein the compound, or its pharmaceutically acceptable salt thereof, is administered in combination with a second active agent. 
     
     
         16 . A method of treating a myeloproliferative neoplasm in a human in need thereof comprising administering to the host an effective amount of a compound having the structure: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         17 . The method of  claim 16 , wherein the myeloproliferative neoplasm is polycythemia vera (PV). 
     
     
         18 . The method of  claim 16 , wherein the myeloproliferative neoplasm is essential thrombocythemia (ET). 
     
     
         19 . The method of  claim 16 , wherein the myeloproliferative neoplasm is myeloid metaplasia with myelofibrosis (MMIM), 
     
     
         20 . The method of  claim 16 , wherein the myeloproliferative neoplasm is hypereosinophilic syndrome (HES). 
     
     
         21 . The method of  claim 16 , wherein the myeloproliferative neoplasm is systemic mast cell disease (SMCD). 
     
     
         22 . The method of  claim 16 , wherein the myeloproliferative neoplasm is myelofibrosis. 
     
     
         23 . The method of  claim 16 , wherein the myeloproliferative neoplasm is primary myelofibrosis 
     
     
         24 . The method of  claim 16 , wherein the compound, or its pharmaceutically acceptable salt thereof, is administered in combination with a second active agent.