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 acute myelogenous leukemia (AML) 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 compound, or its pharmaceutically acceptable salt thereof, is administered in combination with a second active agent. 
     
     
         3 . The method of  claim 1 , wherein the AML is selected from undifferentiated AML, myeloblastic leukemia with minimal cell maturation, myeloblastic leukemia with cell maturation, promyelocytic leukemia, myelomonocytic leukemia, myelomonocytic leukemia with eosinophilia, monocytic leukemia, erythroleukemia, or megakaryoblastic leukemia. 
     
     
         4 . The method of  claim 3 , wherein the AML is undifferentiated AML. 
     
     
         5 . The method of  claim 3 , wherein the AML is myeloblastic leukemia with minimal cell maturation. 
     
     
         6 . The method of  claim 3 , wherein the AML is myeloblastic leukemia with cell maturation. 
     
     
         7 . The method of  claim 3 , wherein the AML is promyelocytic leukemia. 
     
     
         8 . The method of  claim 3 , wherein the AML is myelomonocytic leukemia. 
     
     
         9 . The method of  claim 3 , wherein the AML is myelomonocytic leukemia with eosinophilia. 
     
     
         10 . The method of  claim 3 , wherein the AML is monocytic leukemia. 
     
     
         11 . The method of  claim 3 , wherein the AML is erythroleukemia. 
     
     
         12 . The method of  claim 3 , wherein the AML is megakaryoblastic leukemia. 
     
     
         13 . A method of treating a B-cell lymphoma 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. 
     
     
         14 . The method of  claim 13 , wherein the compound, or its pharmaceutically acceptable salt thereof, is administered in combination with a second active agent. 
     
     
         15 . The method of  claim 13 , wherein the B-cell lymphoma is selected from diffuse large B-cell lymphoma, mediastinal large B-cell lymphoma, nodal marginal zone B-cell lymphoma (NMZL), splenic marginal zone B-cell lymphoma (SMZL), extranodal marginal zone mucosa-associated lymphoid tissue (MALT) B-cell lymphoma, intravascular large B-cell lymphoma, splenic diffuse red pulp small B-cell lymphoma, T cell/histocyte-rich large B-cell lymphoma, primary mediastinal (thymic) large B-cell lymphoma, ALK+ large B-cell lymphoma, large B-cell lymphoma arising in HHV8-associated multicentric Castleman disease, unclassifiable B-cell lymphoma with features intermediate between diffuse large B-cell lymphoma, unclassifiable B-cell lymphoma with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma. 
     
     
         16 . The method of  claim 15 , wherein the B-cell lymphoma is primary mediastinal B-cell lymphoma. 
     
     
         17 . The method of  claim 15 , wherein the B-cell lymphoma is extranodal marginal zone mucosa-associated lymphoid tissue (MALT) B-cell lymphoma. 
     
     
         18 . The method of  claim 15 , wherein the B-cell lymphoma is nodal marginal zone B-cell lymphoma (NMZL). 
     
     
         19 . The method of  claim 15 , wherein the B-cell lymphoma is splenic marginal zone B-cell lymphoma (SMZL). 
     
     
         20 . A method of treating a multiple myeloma 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. 
     
     
         21 . The method of  claim 20 , wherein the compound, or its pharmaceutically acceptable salt thereof, is administered in combination with a second active agent.