CYCLIC NITRO COMPOUNDS, PHARMACEUTICAL COMPOSITIONS THEREOF AND USES THEREOF
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.