Cyclic nitro compounds, pharmaceutical compositions thereof and uses thereof

Abstract

The present invention provides cyclic nitro compound, pharmaceutical compositions of cyclic nitro compounds and methods of using cyclic nitro compounds and/or pharmaceutical compositions thereof to treat or prevent diseases or disorders characterized by abnormal cell proliferation, such as cancer, inflammation, cardiovascular disease and autoimmune disease.

1 - 24 . (canceled) 
     
     
         25 . A method for treating a lymphoma in a human patient, comprising administering to a human patient in need of such treatment a therapeutically effective amount of a compound of Formula I to treat the lymphoma, wherein Formula I is represented by: 
       
         
           
           
               
               
           
         
         or a salt thereof, wherein:
 R 1 , R 2 , R 3  and R 4  are independently hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, heteroaryl, substituted heteroaryl, heteroalkyl, substituted heteroalkyl, heteroarylalkyl, substituted heteroarylalkyl, halogen, hydroxy, or nitro; 
 R 5  and R 6  each represent independently for each occurrence hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, heteroaryl, substituted heteroaryl, heteroalkyl, substituted heteroalkyl, heteroarylalkyl, substituted heteroarylalkyl, halogen, hydroxy, or nitro; 
 R 7  is a substituted acyl selected from the group consisting of substituted —C(O)-aryl, substituted —C(O)-arylalkyl, substituted —C(O)-heteroaryl, and substituted —C(O)-heteroarylalkyl; or R 7  is —C(O)-alkyl or —C(O)-cycloalkyl, each of which is substituted by one or more substituents independently selected from the group consisting of halogen, —CF 3 , —OP(O)(OR 60 )(OR 61 ), and —OP(O)(OH) 2 ; 
 R 60  represents independently for each occurrence alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heteroaryl, or substituted heteroaryl; 
 R 61  represents independently for each occurrence hydrogen, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heteroaryl, or substituted heteroaryl; 
 o is 0, 1, 2, 3 or 4; and 
 provided that two of R 1 , R 2 , R 3 , R 4 , R 5  and R 6  are nitro. 
 
       
     
     
         26 . The method of  claim 25 , wherein R 3  and R 4  are nitro; and R 1 , R 2 , R 5 , and R 6  each represent independently for each occurrence hydrogen or alkyl; and R 7  is —C(O)-alkyl substituted with a halogen. 
     
     
         27 . The method of  claim 26 , wherein variable o is 1. 
     
     
         28 . The method of  claim 25 , wherein the compound is 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         29 . The method of  claim 25 , wherein the compound is 
       
         
           
           
               
               
           
         
       
     
     
         30 . The method of  claim 25 , wherein the administering is intravenous administration. 
     
     
         31 . The method of  claim 28 , wherein the administering is intravenous administration. 
     
     
         32 . The method of  claim 29 , wherein the administering is intravenous administration. 
     
     
         33 . The method of  claim 25 , wherein the method comprises intravenously administering to the human patient in need of such treatment a therapeutically effective amount of said compound in combination with radiation. 
     
     
         34 . The method of  claim 28 , wherein the method comprises intravenously administering to the human patient in need of such treatment a therapeutically effective amount of said compound in combination with radiation. 
     
     
         35 . The method of  claim 29 , wherein the method comprises intravenously administering to the human patient in need of such treatment a therapeutically effective amount of said compound in combination with radiation. 
     
     
         36 . A method for treating a vascularized tumor in a human patient, comprising administering to the human patient in need of such treatment a therapeutically effective amount of a compound of Formula I to treat the vascularized tumor, wherein Formula I is represented by: 
       
         
           
           
               
               
           
         
         or a salt thereof, wherein:
 R 1 , R 2 , R 3  and R 4  are independently hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, heteroaryl, substituted heteroaryl, heteroalkyl, substituted heteroalkyl, heteroarylalkyl, substituted heteroarylalkyl, halogen, hydroxy, or nitro; 
 R 5  and R 6  each represent independently for each occurrence hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, heteroaryl, substituted heteroaryl, heteroalkyl, substituted heteroalkyl, heteroarylalkyl, substituted heteroarylalkyl, halogen, hydroxy, or nitro; 
 R 7  is a substituted acyl selected from the group consisting of substituted —C(O)-aryl, substituted —C(O)-arylalkyl, substituted —C(O)-heteroaryl, and substituted —C(O)-heteroarylalkyl; or R 7  is —C(O)-alkyl or —C(O)-cycloalkyl, each of which is substituted by one or more substituents independently selected from the group consisting of halogen, —CF 3 , —OP(O)(OR 60 )(OR 61 ), and —OP(O)(OH) 2 ; 
 R 60  represents independently for each occurrence alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heteroaryl, or substituted heteroaryl; 
 R 61  represents independently for each occurrence hydrogen, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heteroaryl, or substituted heteroaryl; 
 o is 0, 1, 2, 3 or 4; and 
 provided that two of R 1 , R 2 , R 3 , R 4 , R 5  and R 6  are nitro. 
 
       
     
     
         37 . The method of  claim 36 , wherein R 3  and R 4  are nitro; and R 1 , R 2 , R 5 , and R 6  each represent independently for each occurrence hydrogen or alkyl; and R 7  is —C(O)-alkyl substituted with a halogen. 
     
     
         38 . The method of  claim 37 , wherein variable o is 1. 
     
     
         39 . The method of  claim 36 , wherein the compound is 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         40 . The method of  claim 36 , wherein the compound is 
       
         
           
           
               
               
           
         
       
     
     
         41 . The method of  claim 36 , wherein the administering is intravenous administration. 
     
     
         42 . The method of  claim 39 , wherein the administering is intravenous administration. 
     
     
         43 . The method of  claim 40 , wherein the administering is intravenous administration. 
     
     
         44 . The method of  claim 36 , wherein the method comprises intravenously administering to the human patient in need of such treatment a therapeutically effective amount of said compound in combination with radiation. 
     
     
         45 . The method of  claim 39 , wherein the method comprises intravenously administering to the human patient in need of such treatment a therapeutically effective amount of said compound in combination with radiation. 
     
     
         46 . The method of  claim 40 , wherein the method comprises intravenously administering to the human patient in need of such treatment a therapeutically effective amount of said compound in combination with radiation.