Diphenylethylene compounds and uses thereof

1. A compound of the formula:

or a pharmaceutically acceptable salt, solvate or hydrate thereof,

wherein:

one of R 1 and R 2 is —CN, and the other is —H, substituted or unsubstituted lower alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl;

each occurrence of R c and R d is independently —H, substituted or unsubstituted lower alkyl, or substituted or unsubstituted alkoxy;

R 3 is substituted or unsubstituted lower alkyl substituted or unsubstituted alkoxy or R 3 with R 4 , together form —O—(C(R 16 R 17 )) 2 —O —;

R 4 is substituted or unsubstituted lower alkyl or substituted or unsubstituted alkoxy;

R 5 is substituted or unsubstituted lower alkyl or substituted or unsubstituted alkoxy;

R 6 is —H, substituted or unsubstituted lower alkyl or substituted or unsubstituted alkoxy;

R 7 is —H, substituted or unsubstituted lower alkyl or substituted or unsubstituted alkoxy;

R 8 is —H, substituted or unsubstituted lower alkyl substituted or unsubstituted alkoxy, or R 8 with either R c or with R 7 , together form —O—(C(R 16 R 17 )) 2 —O—;

each occurrence of R 16 and R 17 is independently —H or halogen,

wherein either R 3 with R 4 , together form —O—(C(R 16 R 17 )) 2 —O— or R 8 with either R c or with R 7 , together form —O—(C(R 16 R 17 )) 2 —O—.

2. A compound of claim 1 , wherein R 3 , R 4 and R 5 are alkoxy.

3. A compound of claim 2 , wherein R 3 , R 4 and R 5 are methoxy.

4. A compound of claim 1 , wherein R 7 and R 8 are alkoxy.

5. A compound of claim 1 , wherein R 6 , R 7 and R 8 are alkoxy.

6. A compound of claim 1 , wherein R 1 is —H and R 2 is —CN.

7. A compound of claim 1 , wherein R 1 is —CN and R 2 is —H.

8. A compound of claim 1 , wherein the compound is the E isomer.

9. A compound of claim 1 , wherein the compound is the Z isomer.

10. A compound of the formula:

or a pharmaceutically acceptable salt, solvate or hydrate thereof,

wherein:

one of R 1 and R 2 is —CN, and the other is —H, substituted or unsubstituted lower alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl;

each occurrence of R a , R b , R c and R d is independently —H substituted or unsubstituted lower alkyl, or substituted or unsubstituted alkoxy;

R 3 is substituted or unsubstituted lower alkyl substituted or unsubstituted alkoxy, or R 3 with R a , together from —O—(C(R 16 R 17 )) 2 —O—;

R 4 is —H, substituted or unsubstituted lower alkyl or substituted or unsubstituted alkoxy;

R 5 is substituted or unsubstituted lower alkyl or substituted or unsubstituted alkoxy;

R 6 is substituted or unsubstituted lower alkyl or substituted or unsubstituted alkoxy;

R 7 is —H, substituted or unsubstituted lower alkyl or substituted or unsubstituted alkoxy;

R 8 is substituted or unsubstituted lower alkyl substituted or unsubstituted alkoxy, or R 8 with R c , together form —O—(C(R 16 R 17 )) 2 —O—;

each occurrence of R 16 and R 17 is independently —H or halogen,

wherein either R 3 with R a , together form —O—(C(R 16 R 17 )) 2 —O— or R 8 with R c , together form —O—(C(R 16 R 17 )) 2 —O—.

11. A compound of the formula:

or a pharmaceutically acceptable salt, solvate or hydrate thereof,

wherein:

one of R 1 and R 2 is —CN, and the other is —H, substituted or unsubstituted lower alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl;

each occurrence of R a , R b , R c and R d is independently —H, substituted or unsubstituted lower alkyl or substituted or unsubstituted alkoxy;

R 3 is —H, substituted or unsubstituted lower alkyl substituted or unsubstituted alkoxy, or R 3 with either R a or with R 4 , together form —O—(C(R 16 R 17 )) 2 —O—;

R 4 is —H, substituted or unsubstituted lower alkyl or substituted or unsubstituted alkoxy;

R 5 is —H, substituted or unsubstituted lower alkyl or substituted or unsubstituted alkoxy;

R 6 is —H, substituted or unsubstituted lower alkyl or substituted or unsubstituted alkoxy;

R 7 is —H, substituted or unsubstituted lower alkyl or substituted or unsubstituted alkoxy;

R 8 is —H, substituted or unsubstituted lower alkyl substituted or unsubstituted alkoxy, or R 8 with either R c or with R 7 , together form —O—(C(R 16 R 17 )) 2 —O—;

each occurrence of R 16 and R 17 is independently —H or halogen; and

with the proviso that if one of R 3 or R 5 is H, then the other is not substituted or unsubstituted lower alkyl or substituted or unsubstituted alkoxy and if one of R 6 or R 8 is H, then the other is not substituted or unsubstituted lower alkyl or substituted or unsubstituted alkoxy,

wherein either R 3 with either R a or with R 4 , together form —O—(C(R 16 R 17 )) 2 —O—or R 8 with either R c or with R 7 , together form —O—(C(R 16 R 17 )) 2 —O—.

12. A compound of the formula:

or a pharmaceutically acceptable salt, solvate or hydrate thereof,

wherein:

one of R 1 and R 2 is —CN, and the other is —H, substituted or unsubstituted lower alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl;

each occurrence of R a , R b , R c and R d is independently —H, substituted or unsubstituted lower alkyl or substituted or unsubstituted alkoxy;

R 3 is —H, substituted or unsubstituted lower alkyl substituted or unsubstituted alkoxy, or R 3 with either R a or with R 4 , together form —O—(C(R 16 R 17 )) 2 —O—;

R 4 is —H, substituted or unsubstituted lower alkyl or substituted or unsubstituted alkoxy;

R 5 is —H, substituted or unsubstituted lower alkyl or substituted or unsubstituted alkoxy;

R 6 is —H, substituted or unsubstituted lower alkyl or substituted or unsubstituted alkoxy;

R 7 is —H, substituted or unsubstituted lower alkyl, or substituted or unsubstituted alkoxy;

R 8 is —H, substituted or unsubstituted lower alkyl, substituted or unsubstituted alkoxy, or R 8 with either R c or with R 7 , together form —O—(C(R 16 R 17 )) 2 —O—;

each occurrence of R 16 and R 17 is independently —H or halogen; and

wherein at least one R a and R b and at least one of R c and R d is other than —H,

and wherein either R 3 with either R a or with R 4 , together form —O—(C(R 16 R 17 )) 2 —O— or R 8 with either R c or with R 7 , together form —O—(C(R 16 R 17 ) 2 —O—.

13. A compound of the formula:

or a pharmaceutically acceptable salt, solvate or hydrate thereof,

wherein:

one of R 1 and R 2 is —CN, and the other is —H, substituted or unsubstituted lower alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl;

each occurrence of R a , R b , R c and R d is independently —H, substituted or unsubstituted lower alkyl or substituted or unsubstituted alkoxy;

R 3 is —H, substituted or unsubstituted lower alkyl, substituted or unsubstituted alkoxy, or R 3 with either R a or with R 4 , together form —O—(C(R 16 R 17 )) 2 —O—;

R 4 is —H, substituted or unsubstituted lower alkyl or substituted or unsubstituted alkoxy;

R 5 is —H, substituted or unsubstituted lower alkyl or substituted or unsubstituted alkoxy;

R 6 is —H, substituted or unsubstituted lower alkyl or substituted or unsubstituted alkoxy;

R 7 is —H, substituted or unsubstituted lower alkyl or substituted or unsubstituted alkoxy;

R 8 is —H, substituted or unsubstituted lower alkyl, substituted or unsubstituted alkoxy, or R 8 with either R c or with R 7 , together form —O—(C(R 16 R 17 )) 2 —O—;

each occurrence of R 16 and R 17 is independently —H or halogen; and

wherein either R 3 with either R a or with R 4 , together form —O—(C(R 16 R 17 )) 2 —O— or R 8 with either R c or with R 7 , together form —O—(C(R 16 R 17 )) 2 —O—.

14. A compound of the formula:

or a pharmaceutically acceptable salt, solvate or hydrate thereof,

wherein:

one of R 1 and R 2 is —CN, and the other is substituted or unsubstituted lower alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl;

each occurrence of R a , R b , R c and R d is independently —H, substituted or unsubstituted lower alkyl or substituted or unsubstituted alkoxy;

R 3 is —H, substituted or unsubstituted lower alkyl, substituted or unsubstituted alkoxy, or R 3 with either R a or with R 4 , together form —O—(C(R 16 R 17 )) 2 —O—;

R 4 is —H, substituted or unsubstituted lower alkyl, or substituted or unsubstituted alkoxy;

R 5 is —H, substituted or unsubstituted lower alkyl or substituted or unsubstituted alkoxy;

R 6 is —H, substituted or unsubstituted lower alkyl or substituted or unsubstituted alkoxy;

R 7 is —H, substituted or unsubstituted lower alkyl or substituted or unsubstituted alkoxy;

R 8 is —H, substituted or unsubstituted lower alkyl, substituted or unsubstituted alkoxy, or R 8 with either R c or with R 7 , together form —O—(C(R 16 R 17 )) 2 —O—; and

each occurrence of R 16 and R 17 is independently —H or halogen,

wherein either R 3 with either R a or with R 4 , together form —O—(C(R 16 R 17 )) 2 —O—or R 8 with either R c or with R 7 , together form —O—(C(R 16 R 17 )) 2 —O—.

15. A compound or a pharmaceutically acceptable salt, hydrate or solvate thereof of the structure:

16. A pharmaceutical composition comprising the compound of claim 1 and a pharmaceutically acceptable carrier.

17. The pharmaceutical composition of claim 16 , wherein said composition is suitable for parenteral, transdermal, mucosal, nasal, buccal, rectal, sublingual, or oral administration to a subject.

18. A method for treating colon cancer comprising administering to a subject in need thereof an effective amount of the compound of claim 1 .

19. The method of claim 18 , wherein the compound is the E isomer.

20. The method of claim 18 , wherein the compound is the Z isomer.

21. The method of claim 18 , further comprising administering to said subject an effective amount of one or more anti-cancer agents.

22. The method of claim 21 , wherein at least one of the anti-cancer agents is paclitaxel, docetaxel, cisplatin, carboplatin, oxaliplatin, doxorubicin, gemcitabine, capecitabine, 5-fluorouracil, etoposide, cyclophosphamide, vincristine, vinblastine, topotecan or irinotecan.

23. The method of claim 21 , wherein at least one of the anti-cancer agents is an anti-angiogenic agent, a vascular targeting agent, an immunomodulatory agent or an anti-inflammatory agent.

24. The method of claim 18 , wherein said cancer is refractory to chemotherapy or radiation therapy.