Claims
- 1. A modulator of the structure (I), or a salt thereof:
- 2. The modulator of claim 1, where R6 is hydrogen.
- 3. The modulator of claim 1, where R6 is substituted or unsubstituted C1-8 alkyl.
- 4. The modulator of claim 1, where R6 is halogen.
- 5. The modulator of claim 1, where R3, R4, and R5 are each independently selected from the group consisting of hydrogen, —OR′, and substituted or unsubstituted C1-8 alkyl.
- 6. The modulator of claim 1, where R3, R4, and R5 are each independently selected from the group consisting of —OR′ and hydrogen.
- 7. The modulator of claim 1, where R3, R4, and R5 are each —OR′, where R′ is substituted C1-8 alkyl.
- 8. The modulator of claim 1, where R4 and R5 together with the atom which they substitute form substituted or unsubstituted 5- to 6-membered heterocyclyl containing 1 to 2 oxygen atoms.
- 9. The modulator of claim 1, where Z is CHR1R2 and where R1 and R2 together with Z form C3-10 cycloalkyl with 0 to 3 substituents selected from the group consisting of halogen, —CN, —NO2, —OH, —OR′, —C(O)R′, —CO2R′, —O(CO)R′, —C(O)NR′R″, —OC(O)NR′R″, —SR′, —SOR′, —SO2R′, —SO2NR′R″, —NR′R″, —NR′C(O)R″, —NR′C(O)2R″, —NR′SO2R″, —NR′(CO)NR″R′″, unsubstituted or substituted C1-8 alkyl, unsubstituted or substituted C2-8 alkenyl, unsubstituted or substituted C2-8 alkynyl, unsubstituted or substituted C3-8 cycloalkyl, unsubstituted or substituted C6-10 aryl, unsubstituted or substituted 5- to 10-membered heteroaryl, and unsubstituted or substituted 3- to 10-membered heterocyclyl.
- 10. The modulator of claim 1, where R1 and R2 together with Z form a 3- to 10-membered heterocyclyl with 0 to 3 substituents selected from the group consisting of halogen, —OR, substituted or unsubstituted C1-8 alkyl, substituted or unsubstituted C1-8 alkenyl, substituted or unsubstituted C1-8 alkynyl, substituted or unsubstituted C6-10 aryl, substituted or unsubstituted 5- to 10-membered heteroaryl.
- 11. The modulator of claim 1, where Z is —CHR1R2—.
- 12. The modulator of claim 1, where Z is —N R1R2—.
- 13. The modulator of claim 1, where Z in combination with R1 and R2 is selected from the group consisting of substituted or unsubstituted morpholinyl, substituted or unsubstituted pyrrolidinyl, substituted or unsubstituted piperidinyl, and substituted or unsubstituted piperazinyl.
- 14. The modulator of claim 1, where Z is a substituted or unsubstituted group of the formula:
- 15. The modulator of claim 1, where Z is a substituted or unsubstituted group of the formula:
- 16. The modulator of claim 1, where Z is a substituted or unsubstituted group of the formula:
- 17. The modulator of claim 1, where Z is a substituted or unsubstituted group of the formula:
- 18. The modulator of claim 1, where Z is a substituted or unsubstituted group of the formula:
- 19. The modulator of claim 16, where Z is a substituted or unsubstituted group of the formula:
- 20. The modulator of claim 1, where R7 is substituted or unsubstituted C1-10 alkyl, substituted or unsubstituted C1-10 alkoxy, substituted or unsubstituted aryloxy, or substituted or unsubstituted C3-10 cycloalkyl.
- 21. The modulator of claim 1, where n is 1, 2, or 3.
- 22. The modulator of claim 1, where m is 1 or 2, and each Y is a halogen.
- 23. The modulator of claim 1, where m is 0.
- 24. The modulator of claim 1, where substituted alkyl, substituted alkenyl, substituted alkynyl and substituted cycloalkyl can each independently be substituted 1 to 3 times with halogen, —OR′, —NR′R″, —SR′, —SiR′R″R″′, —OC(O)R′, —C(O)R′, —CO2R′, —CONR′R″, —OC(O)NR′R″, —NR″C(O)R′, —NR′—C(O)NR″R″′, —NR″C(O)2R′, —S(O)R′, —S(O)2R′, —S(O)2NR′R″, —NR′S(O)2R″, —CN, oxo (═O or —O—) or —NO2, where R′, R″ and R″′ each independently hydrogen, halogen, unsubstituted C1-8alkyl, unsubstituted C3-6 cycloalkyl, unsubstituted C2-8 alkenyl, unsubstituted or C2-8 alkynyl, unsubstituted aryl, unsubstituted heteroaryl, unsubstituted or substituted heterocyclyl.
- 25. The modulator of claim 1, where substituted aryl and substituted heteroaryl can each independently be substituted 1 to 3 times with halogen, unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cycloalkyl, —OR′, oxo (═O or —O), —OC(O)R′, —NR′R″, —SR′, —R′, —CN, —NO2, —CO2R′, —CONR′R″, —C(O)R′, —OC(O)NR′R″, —NR″C(O)R′, —NR″C(O)2R′, —NR′—C(O)NR″R″′, —NH—C(NH2)═NH, —NR′C(NH2)═NH, —NH—C(NH2)═NR , —S(O)R′, —S(O)2R′, —S(O)2NR′R″, —NR′S(O)2R″ and —N3, where R′, R″ and R″′ each independently hydrogen, halogen, unsubstituted C1-8 alkyl, unsubstituted C3-6 cycloalkyl, unsubstituted C2-8alkenyl, unsubstituted C2-8alkynyl, unsubstituted or substituted aryl, unsubstituted heteroaryl, unsubstituted heterocyclyl.
- 26. The modulator of claim 1, where substituted heterocyclyl can be substituted 1 to 3 times with halogen, unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cycloalkyl, —OR′, oxo (═O or —O), —OC(O)R′, —NR′R″, —SR′, —R′, —CN, —NO2, —OC(O)NR′R″, —NR″C(O)R′, —NR″C(O)2R′, —NR′—C(O)NR″R″′, —NH—C(NH2)═NH, —NR′C(NH2)═NH, —NH—C(NH2)═NR′, —S(O)R′, —S(O)2NR′R″, —NR′S(O)2R″ and —N3, where R′, R″ and R″′ each independently hydrogen, halogen, unsubstituted C1-8 alkyl, unsubstituted or C3-6 cycloalkyl, unsubstituted C2-8 alkenyl, unsubstituted C2-8 alkynyl, unsubstituted aryl, unsubstituted heteroaryl, unsubstituted heterocyclyl.
- 27. A modulator having the structure (II):
- 28. The modulator of claim 27, where R7 is C1-8 alkoxyalkyloxy.
- 29. The modulator of claim 27, where n is 1.
- 30. A modulator comprising one of the following formulae:
- 31. A pharmaceutical composition comprising the modulator of claim 1 and a pharmaceutically acceptable carrier.
- 32. A pharmaceutical composition comprising the modulator of claim 27 and an pharmaceutically acceptable carrier.
- 33. A pharmaceutical composition comprising the modulator of claim and a pharmaceutically acceptable carrier.
- 34. A pharmaceutical composition comprising a compound of the formulae:
- 35. A method of inhibiting the binding of chemokines I-TAC and/or SDF-1 to a CCXCKR2 receptor, comprising contacting the composition of claim 3234 with a cell that expresses the CCXCKR2 receptor for a time sufficient to inhibit the binding of the chemokines to the CCXCKR2 receptor.
- 36. A method of inhibiting the binding of chemokines I-TAC and/or SDF-1 to a CCXCKR2 receptor, comprising contacting the modulator of claim 1 with a cell that expresses the CCXCKR2 receptor for a time sufficient to inhibit the binding of the chemokines to the CCXCKR2 receptor.
- 37. A method of treating cancer, comprising administering a therapeutically effective amount of the composition of claim 3234 to a cancer patient for a time sufficient to treat the cancer.
- 38. A method of treating cancer, comprising administering a therapeutically effective amount of the modulator of claim 1 to a cancer patient for a time sufficient to treat the cancer.
RELATED APPLICATIONS
[0001] This application claims priority to U.S. provisional application Serial No. 60/434,912 filed Dec. 20, 2002 and U.S. provisional application Serial No. 60/516,151 filed Oct. 30, 2003. The disclosures of the priority applications are incorporated by reference herein in their entirety.
Provisional Applications (2)
|
Number |
Date |
Country |
|
60434912 |
Dec 2002 |
US |
|
60516151 |
Oct 2003 |
US |