Methods and compositions for treating Ewings sarcoma family of tumors

1. A compound of Formula I:

or a pharmaceutically acceptable salt thereof,

wherein R 1 is selected from the group consisting of hydrogen, C 1-6 alkyl, one amino acid, two amino acids linked together, three amino acids linked together,

R 3 is selected from the group consisting hydrogen, halogen, C 1-6 alkyl, C 1-6 alkoxy, —C(═O)NH 2 , —NO 2 , —NH 2 , —OH, —N (R 15 ) 2 , and —SR 15 ;

R 4 , R 5 , R 9 , and R 14 are each independently selected from the group consisting of hydrogen, halogen, C 1-6 alkyl, C 1-6 alkoxy, —C(═O)NH 2 , —NO 2 , —NH 2 , —OH, —NH(R 15 ), —N (R 15 ) 2 , and —SR 15 ;

R 10 is selected from the group consisting of halogen, C 1-6 alkyl, C 1-6 alkoxy, —C(═O)NH 2 , —NO 2 , —NH 2 , —OH, —NH(R 15 ), —N(R 15 ) 2 , and —SR 15 ;

R 11 , R 12 , and R 13 are each independently selected from the group consisting of hydrogen, halogen, C 1-6 alkyl, C 1-6 alkoxy, —C(═O)NH 2 , —NO 2 , —NH 2 , —OH,—NH(R 15 ), —N(R 15 ) 2 , and —SR 15 ;

R 6 is C 1-6 dialkyl amine;

R 7 is selected from the group consisting of hydrogen and C 1-6 alkyl;

R 8 and R 15 are each independently C 1-6 alkyl;

each R 16 is independently hydrogen, —OH, or C 1-6 alkoxy;

n is an integer from 0 to 4;

p is 1 or 3; and

the dashed line represents an optional double bond where said double bond has a configuration selected from the group consisting of cis and trans,

with the proviso that at least one of R 4 , R 5 , R 9 , and R 14 is selected from the group consisting of —NH(R 15 ), —N(R 15 ) 2 , and —SR 15 , or R 3 is selected from the group consisting of —N(R 15 ) 2 , and —SR 15 .

2. The compound of claim 1 having the structure of Formula Ia:

or a pharmaceutically acceptable salt thereof.

3. The compound of claim 1 having the structure of Formula Ib:

or a pharmaceutically acceptable salt thereof.

4. The compound of claim 1 , wherein R 1 is selected from the group consisting of Leu, Leu-Asp, Leu-Asp-Ala, —CH 2 —C(═O) —NHCH 2 COOH, —CH 2 —C(═O)—(CH 2 )C(CH 3 ) 2 ,

5. The compound of claim 1 , wherein R 3 is selected from —N(R 15 ) 2 , and —SR 15 .

6. The compound of claim 1 , wherein R 3 is —N(CH 3 ) 2 .

7. The compound of claim 1 , wherein R 3 is —SCH 3 .

8. The compound of claim 1 having the formula:

or a pharmaceutically acceptable salt thereof.

9. The compound of claim 1 having the formula:

or a pharmaceutically acceptable salt thereof.

10. A compound selected from the group consisting of:

or a pharmaceutically acceptable salt thereof.

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

12. A method for treating a cancer selected from the group consisting of pancreatic cancer and Ewing's sarcoma, said method comprising administering an effective amount of the compound of claim 1 to a subject in need thereof.

13. The method of claim 12 , wherein the subject is human.

14. The method of claim 12 , wherein the cancer comprises a translocation in the EWS gene.

15. A method of killing or inhibiting the growth of a neoplastic cell comprising contacting the cell with an effective amount of the compound of claim 1 , wherein the neoplastic cell is selected from the group consisting of a pancreatic cancer cell and a Ewing's sarcoma cell.

16. The method of claim 15 , wherein the cell is mammalian.

17. The method of claim 15 , wherein the cell is in vitro.

18. The method of claim 15 , wherein the cell is in vivo.

19. The method of claim 15 , wherein comprises the cell, said cancer the cell comprises a translocation in the EWS gene.

20. The compound of claim 1 selected from the group consisting of