Compounds and methods for modulating Interleukin-2-inducible T-cell kinase

1. A compound of Formula (IIA):

wherein:

R 1 is hydrogen, halogen, —CX 1 3 , —CHX 1 2 , —CH 2 X 1 , —OCX 1 3 , —OCH 2 X 1 , —OCHX 1 2 , —CN, —SO n1 R 1D , —SO v1 NR 1A R 1B , —NHC(O)NR 1A R 1B , —N(O) m1 , —NR 1A R 1B , —C(O)R 1C , —C(O)—OR 1C , —C(O)NR 1A R 1B , —OR 1D , —NR 1A SO 2 R 1D , —NR 1A C(O)R 1C , —NR 1A C(O)OR 1C , —NR 1A OR 1C , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;

R 3 is hydrogen, halogen, —CX 3 3 , —CHX 3 2 , —CH 2 X 3 , —OCX 3 3 , —OCH 2 X 3 , —OCHX 3 2 , —CN, —SO n3 R 3D , —SO v3 NR 3A R 3B , —NHC(O)NR 3A R 3B , —N(O) m3 , —NR 3A R 3B , —C(O)R 3C , —C(O)—OR 3C , —C(O)NR 3A R 3B , —OR 3D , —NR 3A SO 2 R 3D , —NR 3A C(O)R 3C , —NR 3A C(O)OR 3C , —NR 3A OR 3C , unsubstituted or substituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;

R 5 is unsubstituted or substituted cycloalkyl, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;

L 3 is —C(O)—, a bond, —N(R 6 )—, or —C(O)N(R 6 )—;

R 6 is hydrogen or methyl;

L 4 is substituted or unsubstituted 5 to 8 membered monocyclic heterocycloalkylene;

E is —C(O)CH═CH 2 ;

R 1A , R 1B , R 1C , R 1D , R 3A , R 3B , R 3C , and R 3D are each independently hydrogen, —CX 3 , —CN, —COOH, —CONH 2 , —CHX 2 , —CH 2 X, unsubstituted alkyl, unsubstituted heteroalkyl, unsubstituted cycloalkyl, unsubstituted heterocycloalkyl, unsubstituted aryl, or unsubstituted heteroaryl;

X, X 1 , and X 3 are each independently —F, —Cl, —Br, or —I;

n1 and n3 are independently an integer from 0 to 4; and

m1, m3, v1, and v3 are independently 1 or 2.

2. The compound of claim 1 wherein:

R 1 is hydrogen, halogen, —CX 1 3 , —CH 1 2 , CH 2 X 1 , —OCX 1 3 , —OCH 2 X 1 , —OCHX 1 2 , unsubstituted alkyl, or unsubstituted heteroalkyl; and

R 3 is hydrogen, halogen, —CX 3 3 , —CHX 3 2 , —CH 2 X 3 , —OCX 3 3 , —OCH 2 X 3 , —OCHX 3 2 , —CN, unsubstituted alkyl, or unsubstituted heteroalkyl.

3. The compound of claim 2 , wherein:

R 1 is hydrogen, halogen, —CH 3 , —CH 2 CH 3 , —CX 1 3 , —CHX 1 2 , —CH 2 X 1 , —OCH 3 , —OCX 1 3 , —OCH 2 X 1 , or —OCHX 1 2 ; and

R 3 is hydrogen, halogen, —CH 3 , —CH 2 CH 3 , —CX 3 3 , —CHX 3 2 , —CH 2 X 3 , —OCH 3 , —OCX 3 3 , —OCH 2 X 3 , —OCHX 3 2 , or CN.

4. The compound of claim 1 , wherein R 1A , R 1B , R 1C , R 1D , R 3A , R 3B , R 3C , and R 3D are hydrogen.

5. The compound of claim 1 , wherein R 5 is substituted or unsubstituted cycloalkyl.

6. The compound of claim 5 , wherein R 5 is unsubstituted cyclopropyl, unsubstituted cyclobutyl, or unsubstituted cyclopentyl.

7. The compound of claim 1 , wherein R 5 is substituted or unsubstituted (C 1 -C 4 ) alkyl.

8. The compound of claim 1 , wherein R 5 is substituted or unsubstituted pyridyl, substituted or unsubstituted thienyl, substituted or unsubstituted furanyl, substituted or unsubstituted pyrrolyl, substituted or unsubstituted imidazolyl, substituted or unsubstituted pyrazolyl, substituted or unsubstituted thiazolyl, substituted or unsubstituted isothiazolyl, substituted or unsubstituted oxazolyl, or substituted or unsubstituted isoxazolyl.

9. The compound of claim 1 , wherein L 3 is —C(O)—.

10. The compound of claim 1 , wherein L 4 is a methyl-substituted 5 to 8 membered monocyclic heterocycloalkylene, an ethyl-substituted 5 to 8 membered monocyclic heterocycloalkylene, a cyano-substituted 5 to 8 membered monocyclic heterocycloalkylene, a halo-substituted 5 to 8 membered monocyclic heterocycloalkylene, or an unsubstituted 5 to 8 membered monocyclic heterocycloalkylene.

11. The compound of claim 1 , wherein L 4 is

12. A pharmaceutical composition comprising the compound of claim 1 and a pharmaceutically acceptable excipient.

13. A method of treating T-cell lymphoma in a patient in need thereof, the method comprising administering to the patient an effective amount of the compound of claim 1 .

14. The method of claim 13 , wherein the T-cell lymphoma is cutaneous T-cell lymphoma or peripheral T-cell lymphoma.

15. A method of treating T-cell lymphoma in a patient in need thereof, the method comprising administering to the patient an effective amount of a compound; wherein the compound is

16. The method of claim 15 , wherein the T-cell lymphoma is cutaneous T-cell lymphoma.

17. The method of claim 15 , wherein the T-cell lymphoma is peripheral T-cell lymphoma.

18. A pharmaceutical composition comprising a compound and a pharmaceutically acceptable excipient; wherein the compound is

19. A method of treating T-cell lymphoma in a patient in need thereof, the method comprising administering to the patient an effective amount of the pharmaceutical composition of claim 18 .

20. The method of claim 19 , wherein the T-cell lymphoma is cutaneous T-cell lymphoma or peripheral T-cell lymphoma.

21. A method of treating T-cell lymphoma in a patient in need thereof, the method comprising administering to the patient an effective amount of a compound having the formula:

22. The method of claim 21 , wherein the T-cell lymphoma is cutaneous T-cell lymphoma.

23. The method of claim 21 , wherein the T-cell lymphoma is peripheral T-cell lymphoma.

24. The method of claim 21 , wherein the T-cell lymphoma is peripheral T-cell lymphoma, unspecified.

25. A pharmaceutical composition comprising a compound and a pharmaceutically acceptable excipient; wherein the compound is:

26. A method of treating T-cell lymphoma in a patient in need thereof, the method comprising administering to the patient an effective amount of the pharmaceutical composition of claim 25 .

27. The method of claim 26 , wherein the T-cell lymphoma is cutaneous T-cell lymphoma.

28. The method of claim 26 , wherein the T-cell lymphoma is peripheral T-cell lymphoma.

29. The method of claim 26 , wherein the T-cell lymphoma is peripheral T-cell lymphoma, unspecified.