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 . A compound of structural Formula (I):
or salts, solvates or hydrates thereof wherein:
R 1 , R 2 , R 3 and R 4 are each independently, hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, heteroaryl, substituted heteroaryl, heteroalkyl, substituted heteroalkyl, heteroarylalkyl, substituted heteroarylalkyl, halo, hydroxy or nitro;
each R 5 and R 6 are each independently, hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, heteroaryl, substituted heteroaryl, heteroalkyl, substituted heteroalkyl, heteroarylalkyl, substituted heteroarylalkyl, halo, hydroxy or nitro;
o is 0, 1, 2, 3 or 4;
R 7 is substituted alkyl, substituted arylalkyl, substituted heteroalkyl, substituted heteroaryl, substituted heteroarylalkyl, substituted acyl, substituted alkoxycarbonyl, substituted phosphonyl or substituted sulfonyl;
provided that at least one of R 1 , R 2 , R 3 , R 4 , R 5 and R 6 are nitro.
2 . The compound of claim 1 in which at least two of R 1 , R 2 , R 3 , R 4 , R 5 and R 6 are nitro.
3 . The compound of claim 1 in which R 1 , R 2 , R 3 and R 4 are each independently, hydrogen, alkyl or nitro and each R 5 and R 6 are each independently, hydrogen, alkyl or nitro.
4 . The compound of claim 1 in which R 7 is substituted alkyl, substituted acyl, substituted alkoxycarbonyl, substituted phosphonyl or substituted sulfonyl.
5 . The compound of claim 1 in which R 7 is alkyl, acyl, alkoxycarbonyl, phosphonyl or sulfonyl substituted with one or more halogen, —CF 3 or —OS(O) 2 R 8 wherein R 8 is alkyl, substituted alkyl, aryl or substituted aryl.
6 . The compound of claim 1 in which R 3 and R 4 are nitro.
7 . The compound of claim 1 in which R 1 , R 2 , R 3 and R 4 are each independently, hydrogen, alkyl or nitro, each R 5 and R 6 are each independently, hydrogen, alkyl or nitro and R 7 is substituted alkyl, substituted acyl, substituted alkoxycarbonyl, substituted phosphonyl or substituted sulfonyl.
8 . The compound of claim 1 in which R 1 , R 2 , R 3 and R 4 are each independently, hydrogen, alkyl or nitro, each R 5 and R 6 are each independently, hydrogen, alkyl or nitro and R 7 is alkyl, acyl, alkoxycarbonyl, phosphonyl or sulfonyl substituted with one or more halogen, —CF 3 or —OS(O) 2 R 8 wherein R 8 is alkyl, substituted alkyl, aryl or substituted aryl.
9 . The compound of claim 1 in which R 1 and R 2 are each independently, hydrogen, alkyl or nitro, R 3 and R 4 are nitro, each R 5 and R 6 are each independently, hydrogen, alkyl or nitro and R 7 is substituted alkyl, substituted acyl, substituted alkoxycarbonyl, substituted phosphonyl or substituted sulfonyl.
10 . The compound of claim 1 in which R 1 and R 2 are each independently, hydrogen, alkyl or nitro, R 3 and R 4 are nitro, each R 5 and R 6 are each independently, hydrogen, alkyl or nitro and R 7 is alkyl, acyl, alkoxycarbonyl, phosphonyl or sulfonyl substituted with one or more halogen, —CF 3 or —OS(O) 2 R 8 wherein R 8 is alkyl, substituted alkyl, aryl or substituted aryl.
11 . The compound of any of claims 1-10 in which o is 1.
12 . The compound of claim 1 in which R 1 and R 2 are each independently, hydrogen, alkyl or nitro, R 3 and R 4 are nitro, each R 5 and R 6 are each independently, hydrogen, alkyl or nitro and R 7 is alkyl or acyl substituted with one or more halogen or —CF 3 and o is 1.
13 . The compound of claim 1 in which R 1 and R 2 are hydrogen, R 3 and R 4 are nitro, R 5 and R 6 are hydrogen, R 7 is alkyl or acyl substituted with one or more halogen or —CF 3 and o is 1.
14 . The compound of claim 1 having the structure:
wherein each X is independently —F, —Cl, —Br, —I or —OS(O) 2 R 8 where R 8 is methyl, CF 3 , phenyl or tolyl and each p is independently 1, 2, 3, or 4.
15 . The compound of claim 1 having the structure:
wherein each X is independently —F, —Cl, —Br, —I or —OS(O) 2 R 8 where R 8 is methyl, CF 3 , phenyl or tolyl.
16 . A pharmaceutical composition comprising the compound of claim 1 and a pharmaceutically acceptable vehicle.
17 . A method for treating or preventing cancer in a patient comprising administering to a patient in need of such treatment or prevention a therapeutically effective amount of the compound of claim 1 .
18 . The method of any one of claim 16 or 17 in which the cancer is breast cancer, renal cancer, brain cancer, colon cancer, colorectal cancer, prostrate cancer or lung cancer.
19 . A method for treating tumor cells with a reduced intracellular environment in a patient, comprising administering to the patient in need of treatment a therapeutically effective amount of the compound of claim 1 .
20 . A method for treating or preventing solid tumors in a patient, comprising administering to the patient in need of treatment or prevention a therapeutically effective amount of the compound of claim 1 .
21 . A method for treating or preventing leukemias and lymphomas in a patient, comprising administering to the patient in need of treatment or prevention a therapeutically effective amount of the compound of claim 1 .
22 . A method for treating or preventing inflammation in a patient, comprising administering to the patient in need of treatment or prevention a therapeutically effective amount of the compound of claim 1 .
23 . A method for treating or preventing autoimmune disease in a patient, comprising administering to the patient in need of treatment or prevention a therapeutically effective amount of the compound of claim 1 .
24 . A method for treating or preventing cardiovascular disease in a patient, comprising administering to the patient in need of treatment or prevention a therapeutically effective amount of the compound of claim 1 .