Some content of this application is unavailable at the moment.
If this situation persist, please contact us atFeedback&Contact
1. (WO2010114894) SUBSTITUTED HETEROCYCLIC COMPOUNDS
Note: Text based on automatic Optical Character Recognition processes. Please use the PDF version for legal matters

What is claimed is:

1. A compound of formula I:


or a salt or ester thereof, wherein: one of Zi and Z2 is CR3 the other is N;

X2 and X4 are independently C(O) or CH2;

X3 is CRaRb;

Y is unsubstituted or substituted C1-C6 alkyl linker or a bond; m is O, 1 , 2, 3, 4;

Ri is unsubstituted or substituted C5-C10 aryl, unsubstituted or substituted heteroaryl comprising 1-4 heteroatoms selected from N, O and S, unsubstituted or substituted C3-C10 carbocycle, unsubstituted or substituted heterocycle comprising 1-4 heteroatoms selected from N, O and S, C(O)RC or S(O)2Rc;

R3 is H, halogen, unsubstituted or substituted C1-C8 alkyl, unsubstituted or substituted C5-C10 aryl, unsubstituted or substituted heteroaryl comprising 1-4 heteroatoms selected from N, O and S, unsubstituted or substituted C3-C10 carbocycle or unsubstituted or substituted heterocycle comprising 1-4 heteroatoms selected from N, O and S; each R4 is independently hydroxyl, halogen, unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C1-C6 alkoxyl, amino, unsubstituted or substituted C1- C6 alkylamino, unsubstituted or substituted di-(C1-C6) alkylamino, unsubstituted or substituted C5-C10 aryl, unsubstituted or substituted heteroaryl comprising 1-4 heteroatoms selected from N, O and S, unsubstituted or substituted C3-C10 carbocycle, unsubstituted or substituted heterocycle comprising 1-4 heteroatoms selected from N, O and S or any two adjacent R4'S, together with the atoms to which they are attached, form a 5- to 7-member ring optionally comprising 1-4 optionally comprising 1-4 heteroatoms selected from N, O and S;

Ra and Rb are independently H, unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C5-C10 aryl, unsubstituted or substituted heteroaryl comprising 1-4 heteroatoms selected from N, O and S, unsubstituted or substituted C3-C10 carbocycle, unsubstituted or substituted heterocycle comprising 1-4 heteroatoms selected from N, O and S; and

Rc is H, unsubstituted or substituted C1-C8 alkyl, unsubstituted or substituted C5- Cio aryl, unsubstituted or substituted heteroaryl comprising 1-4 heteroatoms selected from N, O and S, unsubstituted or substituted C3-C10 carbocycle or unsubstituted or substituted heterocycle comprising 1-4 heteroatoms selected from N, O and S.

2. The compound of claim 1 , wherein the compound is a compound of formula Ia:


or a salt or ester thereof, wherein,

X2 and X4 are independently C(O) or CH2;

X3 is CRaRb;

Y is unsubstituted or substituted C1-C6 alkyl linker or a bond; m is O, 1 , 2, 3, 4;

Ri is unsubstituted or substituted C5-C10 aryl, unsubstituted or substituted heteroaryl comprising 1-4 heteroatoms selected from N, O and S, unsubstituted or substituted C3-C10 carbocycle, unsubstituted or substituted heterocycle comprising 1-4 heteroatoms selected from N, O and S, C(O)RC or S(O)2Rc;

R3 is H, halogen, unsubstituted or substituted C1-C8 alkyl, unsubstituted or substituted C5-C10 aryl, unsubstituted or substituted heteroaryl comprising 1-4 heteroatoms selected from N, O and S, unsubstituted or substituted C3-C10 carbocycle or unsubstituted or substituted heterocycle comprising 1-4 heteroatoms selected from N, O and S; each R4 is independently hydroxyl, halogen, unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C1-C6 alkoxyl, amino, unsubstituted or substituted C1- C6 alkylamino, unsubstituted or substituted di-(C1-C6) alkylamino, unsubstituted or substituted C5-C10 aryl, unsubstituted or substituted heteroaryl comprising 1-4 heteroatoms selected from N, O and S, unsubstituted or substituted C3-C10 carbocycle, unsubstituted or substituted heterocycle comprising 1-4 heteroatoms selected from N, O and S or any two adjacent R4'S, together with the atoms to which they are attached, form a 5- to 7-member ring optionally comprising 1-4 optionally comprising 1-4 heteroatoms selected from N, O and S;

Ra and Rb are independently H, unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C5-C10 aryl, unsubstituted or substituted heteroaryl comprising 1-4 heteroatoms selected from N, O and S, unsubstituted or substituted C3-C10 carbocycle, unsubstituted or substituted heterocycle comprising 1-4 heteroatoms selected from N, O and S; and

Rc is H, unsubstituted or substituted C1-C8 alkyl, unsubstituted or substituted C5- Cio aryl, unsubstituted or substituted heteroaryl comprising 1-4 heteroatoms selected from N, O and S, unsubstituted or substituted C3-C10 carbocycle or unsubstituted or substituted heterocycle comprising 1-4 heteroatoms selected from N, O and S.

3. The compound of claim 2, wherein X2 and X4 are each CH2, X3 is CRaRb where Ra and Rb are each H, and R3 is H.

4. The compound of claim 2, wherein m is 0, Y is unsubstituted or substituted C1-C6 alkyl linker and Ri is unsubstituted or substituted C5-C10 aryl.

5. The compound of claim 4, wherein Ri is unsubstituted or substituted phenyl.

6. The compound of claim 1 , wherein the compound is a compound of formula Ib:


or a salt or ester thereof, wherein,

X2 and X4 are independently C(O) or CH2;

X3 is CRaRb;

Y is unsubstituted or substituted C1-C6 alkyl linker or a bond; m is O, 1 , 2, 3, 4;

Ri is unsubstituted or substituted C5-C10 aryl, unsubstituted or substituted heteroaryl comprising 1-4 heteroatoms selected from N, O and S, unsubstituted or substituted C3-C10 carbocycle, unsubstituted or substituted heterocycle comprising 1-4 heteroatoms selected from N, O and S, C(O)RC or S(O)2Rc; each R4 is independently hydroxyl, halogen, unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C1-C6 alkoxyl, amino, unsubstituted or substituted C1- C6 alkylamino, unsubstituted or substituted di-(C1-C6) alkylamino, unsubstituted or substituted C5-C10 aryl, unsubstituted or substituted heteroaryl comprising 1-4 heteroatoms selected from N, O and S, unsubstituted or substituted C3-C10 carbocycle, unsubstituted or substituted heterocycle comprising 1-4 heteroatoms selected from N, O and S or any two adjacent R4'S, together with the atoms to which they are attached, form a 5- to 7-member ring optionally comprising 1-4 optionally comprising 1-4 heteroatoms selected from N, O and S;

Ra and Rb are independently H, unsubstituted or substituted Ci-C6 alkyl, unsubstituted or substituted C5-C10 aryl, unsubstituted or substituted heteroaryl comprising 1-4 heteroatoms selected from N, O and S, unsubstituted or substituted C3-C10 carbocycle, unsubstituted or substituted heterocycle comprising 1-4 heteroatoms selected from N, O and S; and

Rc is H, unsubstituted or substituted C1-C8 alkyl, unsubstituted or substituted C5- Cio aryl, unsubstituted or substituted heteroaryl comprising 1-4 heteroatoms selected from N, O and S, unsubstituted or substituted C3-C10 carbocycle or unsubstituted or substituted heterocycle comprising 1-4 heteroatoms selected from N, O and S.

7. The compound of claim 6, wherein X2 and X4 are each CH2, X3 is CRaRb, and Ra and Rb are each H.

8. The compound of claim 7, wherein m is 0, Y is unsubstituted or substituted C1-C6 alkyl linker and Ri is unsubstituted or substituted C5-C10 aryl.

9. The compound of claim 8, wherein Ri is unsubstituted or substituted phenyl.

10. The compound of claim 1, wherein said compound is selected from the group consisting of:






and pharmaceutically acceptable salts thereof

1. A compound of formula II:


or a salt or ester thereof, wherein: one of Zi and Z2 is CR3 the other is N;

Z is -(CH2)n-, -CH2-O-(CH2)n- or a bond; m is O, 1 , 2, 3, 4; n is 1, 2, 3, 4, 5, 6;

R3 is H, halogen, unsubstituted or substituted C1-C8 alkyl, unsubstituted or substituted C5-C10 aryl, unsubstituted or substituted heteroaryl comprising 1-4 heteroatoms selected from N, O and S, unsubstituted or substituted C3-C10 carbocycle or unsubstituted or substituted heterocycle comprising 1-4 heteroatoms selected from N, O and S; each R4 is independently hydroxyl, halogen, unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C1-C6 alkoxyl, amino, unsubstituted or substituted Ci- C6 alkylamino, unsubstituted or substituted di-(C1-C6) alkylamino, unsubstituted or substituted C5-C10 aryl, unsubstituted or substituted heteroaryl comprising 1-4 heteroatoms selected from N, O and S, unsubstituted or substituted C3-C10 carbocycle, unsubstituted or substituted heterocycle comprising 1-4 heteroatoms selected from N, O and S or any two adjacent R4'S, together with the atoms to which they are attached, form a 5- to 7-member ring optionally comprising 1-4 optionally comprising 1-4 heteroatoms selected from N, O and S; and

R5 is H, unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C5- Cio aryl, unsubstituted or substituted heteroaryl comprising 1-4 heteroatoms selected from N, O and S, unsubstituted or substituted C3-C10 carbocycle or unsubstituted or substituted heterocycle comprising 1-4 heteroatoms selected from N, O and S.

12. The compound of claim 11 , wherein the compound is a compound of formula Ha:


or a salt or ester thereof, wherein,

Z is -(CH2)n-, -CH2-O-(CH2)n- or a bond; m is O, 1 , 2, 3, 4; n is 1, 2, 3, 4, 5, 6;

R3 is H, halogen, unsubstituted or substituted C1-C8 alkyl, unsubstituted or substituted C5-C10 aryl, unsubstituted or substituted heteroaryl comprising 1-4 heteroatoms selected from N, O and S, unsubstituted or substituted C3-C10 carbocycle or unsubstituted or substituted heterocycle comprising 1-4 heteroatoms selected from N, O and S; each R4 is independently hydroxyl, halogen, unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C1-C6 alkoxyl, amino, unsubstituted or substituted C1- C6 alkylamino, unsubstituted or substituted di-(C1-C6) alkylamino, unsubstituted or substituted C5-C10 aryl, unsubstituted or substituted heteroaryl comprising 1-4 heteroatoms selected from N, O and S, unsubstituted or substituted C3-C10 carbocycle, unsubstituted or substituted heterocycle comprising 1-4 heteroatoms selected from N, O and S or any two adjacent R4'S, together with the atoms to which they are attached, form a 5- to 7-member ring optionally comprising 1-4 optionally comprising 1-4 heteroatoms selected from N, O and S; and

R5 is H, unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C5- Cio aryl, unsubstituted or substituted heteroaryl comprising 1-4 heteroatoms selected from N, O and S, unsubstituted or substituted C3-C10 carbocycle or unsubstituted or substituted heterocycle comprising 1-4 heteroatoms selected from N, O and S.

13. The compound of claim 12, wherein R3 is H, Z is -(CH2)n- or a bond, and R5 is unsubstituted or substituted C5-C10 aryl.

14. The compound of claim 11 , wherein the compound is a compound of formula lib:


or a salt or ester thereof, wherein,

Z is -(CH2)n-, -CH2-O-(CH2)n- or a bond; m is O, 1 , 2, 3, 4; n is 1, 2, 3, 4, 5, 6; each R4 is independently hydroxyl, halogen, unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C1-C6 alkoxyl, amino, unsubstituted or substituted Ci- C6 alkylamino, unsubstituted or substituted di-(C1-C6) alkylamino, unsubstituted or substituted C5-C10 aryl, unsubstituted or substituted heteroaryl comprising 1-4 heteroatoms selected from N, O and S, unsubstituted or substituted C3-C10 carbocycle, unsubstituted or substituted heterocycle comprising 1-4 heteroatoms selected from N, O and S or any two adjacent R4'S, together with the atoms to which they are attached, form a 5- to 7-member ring optionally comprising 1-4 optionally comprising 1-4 heteroatoms selected from N, O and S; and

R5 is H, unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C5- Cio aryl, unsubstituted or substituted heteroaryl comprising 1-4 heteroatoms selected from N, O and S, unsubstituted or substituted C3-C10 carbocycle or unsubstituted or substituted heterocycle comprising 1-4 heteroatoms selected from N, O and S.

15. The compound of claim 14, wherein Z is -(CH2)n- or a bond, and R5 is unsubstituted or substituted C5-C10 aryl.

16. The compound of claim 11 , wherein said compound is selected from the group consisting of:
and pharmaceutically acceptable salts thereof.

17. A pharmaceutical composition comprising a compound of claim 1 or 11 and one or more pharmaceutically acceptable carriers.

18. A method of treating a cell proliferative disorder by administering to a subject in need thereof, a therapeutically effective amount of a compound of claim 1 or 11 , or a pharmaceutically acceptable salt, prodrug, metabolite, analog or derivative thereof, in combination with a pharmaceutically acceptable carrier, such that the disorder is treated.

19. A method of treating cancer by administering to a subject in need thereof, a therapeutically effective amount of a compound of claim 1 or 11 , or a pharmaceutically acceptable salt, prodrug, metabolite, analog or derivative thereof, in combination with a pharmaceutically acceptable carrier, such that the cancer is treated.

20. A method of selectively inducing cell death in precancerous or cancerous cells by contacting a cell with an effective amount of a compound of claim 1 or 11 , or a pharmaceutically acceptable salt, prodrug, metabolite, analog or derivative thereof, in combination with a pharmaceutically acceptable carrier, such that contacting the cell results in selective induction of cell death in the precancerous or cancer cells.