Claims
- 1. A method of treating a CCR4-mediated condition or disease in a subject, said method comprising administering to a subject in need of such treatment an effective amount of a compound having the formula:
- 2. A method in accordance with claim 1, wherein X is —NH—.
- 3. A method in accordance with claim 1, wherein X is —SO2NH—.
- 4. A method in accordance with claim 1, wherein Ar1 and Ar2 are each substituted or unsubstituted members independently selected from the group consisting of:
- 5. A method in accordance with claim 2, wherein Ar1 is substituted heteroaryl and Ar2 is substituted or unsubstituted aryl.
- 6. A method in accordance with claim 5, wherein said Ar1 is a substituted heteroaryl selected from the group consisting of substituted thiazolyl, substituted thienyl, and substituted furanyl.
- 7. A method in accordance with claim 5, wherein said Ar2 is a substituted or unsubstituted phenyl or a substituted or unsubstituted naphthyl.
- 8. A method in accordance with claim 3, wherein Ar2 is a phenyl group having from 1 to 4 substituents independently selected from the group consisting of halogen, hydroxy, (C1-C4)alkyl, (C1-C4)alkoxy, (C1-C4)alkylthio, (C1-C4)haloalkyl, (C1-C4)haloalkoxy, nitro, cyano, (C1-C4)acyl, amino, (C1-C4)alkylamino, and di(C1-C4)alkylamino.
- 9. A method in accordance with claim 8, wherein said phenyl group has from 1 to 3 substituents independently selected from the group consisting of halogen, (C1-C4)haloalkyl, (C1-C4)haloalkoxy, nitro, cyano, and (C1-C4)acyl.
- 10. A method in accordance with claim 3, wherein Ar1 is a substituted or unsubstituted monocyclic or bicyclic heterocycle.
- 11. A method in accordance with claim 10, wherein said heterocycle is selected from the group consisting of pyrrolyl, pyrazolyl, imidazolyl, pyrazinyl, oxazolyl, isoxazolyl, thiazolyl, furyl, thienyl, pyridyl, pyrimidyl, benzothiazolyl, benzoxadiazolyl, purinyl, benzimidazolyl, indolyl, isoquinolyl, quinoxalinyl and quinolyl.
- 12. A method in accordance with claim 11, wherein said heterocycle is selected from the group consisting of thienyl, thiazolyl and benzoxadiazolyl.
- 13. A method in accordance with claim 1, wherein said CCR4-mediated condition or disease is selected from the group consisting of contact hypersensitivity, atopic dermatitis, allergic airway hypersensitivity, allergic rhinitis, atherosclerosis, septic shock, angina, myocardial infarction, restenosis, ischemia/reperfusion injury, multiple sclerosis, rheumatoid arthritis, type I diabetes, psoriasis, cancer and HIV infection.
- 14. A method in accordance with claim 1, wherein said CCR4-mediated condition or disease is psoriasis, contact hypersensitivity or atopic dermatitis.
- 15. A method in accordance with claim 14, wherein said CCR4-mediated condition or disease is psoriasis.
- 16. A method in accordance with claim 14, wherein said CCR4-mediated condition or disease is contact hypersensitivity.
- 17. A method in accordance with claim 14, wherein said CCR4-mediated condition or disease is atopic dermatitis.
- 18. A method in accordance with claim 1, wherein said CCR4-mediated condition or disease is a disease of the airway.
- 19. A method in accordance with claim 18, wherein said disease of the airway is selected from the group consisting of allergic asthma and allergic rhinitis.
- 20. A method in accordance with claim 18, wherein said disease of the airway is allergic asthma.
- 21. A method in accordance with claim 1, wherein said CCR4-mediated condition or disease is a disease of innate immunity.
- 22. A method in accordance with claim 21, wherein said disease of innate immunity is septic shock.
- 23. A method in accordance with claim 1, wherein said CCR4-mediated condition or disease is atherosclerosis.
- 24. A method in accordance with claim 1, wherein said CCR4-mediated condition or disease is a disease or condition characterized by platelet aggregation or thrombosis.
- 25. A method in accordance with claim 24, wherein said CCR4-mediated disease or condition is selected from the group consisting of angina, myocardial infarction, restenosis, stroke and ischemia/reperfusion injury.
- 26. A method in accordance with claim 1, wherein said CCR4-mediated condition or disease is an allergic condition and said compound is used alone or in combination with at least one therapeutic agent wherein said therapeutic agent is an antihistamine.
- 27. A method in accordance with claim 1, wherein said CCR4-mediated disease or condition is psoriasis and said compound is used alone or in combination with at least one therapeutic agent selected from a corticosteroid, a lubricant, a keratolytic agent, a vitamin D3 derivative, PUVA, or anthralin.
- 28. A method in accordance with claim 1, wherein said CCR4-mediated disease or condition is atopic dermatitis and said compound is used alone or in combination with at least one therapeutic agent selected from a lubricant and corticosteroid.
- 29. A method in accordance with claim 1, wherein said CCR4-mediated condition or disease is asthma and said compound is used alone or in combination with at least one therapeutic agent selected from a B2-agonist and a corticosteroid.
- 30. A method in accordance with claim 1, wherein said compound interferes with the interaction between CCR4 and a ligand.
- 31. A method in accordance with claim 1, wherein said administration is oral or intravenous.
- 32. A method in accordance with claim 1, wherein said subject is selected from the group consisting of human, rat, dog, cow, horse, and mouse.
- 33. A method in accordance with claim 1, wherein said subject is human.
- 34. A method in accordance with claim 1, wherein said compound is selected from the group consisting of
- 35. A method in accordance with claim 1, wherein said CCR4-mediated disease or condition is selected from the group consisting of multiple sclerosis, rheumatoid arthritis, type I diabetes, psoriasis, cancer and HIV infection; Ar1 is a substituted heterocycle; X is —SO2NH—; and Ar2 is a substituted phenyl.
- 36. A method in accordance with claim 1, wherein said CCR4-mediated disease or condition is selected from the group consisting of multiple sclerosis, rheumatoid arthritis, type I diabetes, psoriasis, cancer and HIV infection; Ar1 is a substituted heterocycle; X is —NH—; and Ar2 is naphthyl.
- 37. A pharmaceutical composition for the treatment of a CCR4-mediated disease or condition, said composition comprising a pharmaceutically acceptable carrier and an effective amount of a compound which inhibits the binding of MDC or TARC to CCR4, said compound having the formula:
- 38. A composition of claim 37, wherein X is —NH—.
- 39. A composition of claim 37, wherein X is —SO2NH—.
- 40. A composition of claim 37, wherein Ar1 and Ar2 are each substituted or unsubstituted members independently selected from the group consisting of:
- 41. A composition of claim 37, wherein Ar1 is substituted heteroaryl and Ar2 is substituted or unsubstituted aryl.
- 42. A composition of claim 41, wherein said Ar1 is a substituted heteroaryl selected from the group consisting of substituted thiazolyl, substituted thienyl, and substituted furanyl.
- 43. A composition of claim 41, wherein said Ar2 is a substituted or unsubstituted phenyl or a substituted or unsubstituted naphthyl.
- 44. A composition of claim 41, wherein Ar1 is a phenyl group having from 1 to 4 substituents independently selected from the group consisting of halogen, hydroxy, (C1-C4)alkyl, (C1-C4)alkoxy, (C1-C4)alkylthio, (C1-C4)haloalkyl, (C1-C4)haloalkoxy, nitro, cyano, (C1-C4)acyl, amino, (C1-C4)alkylamino, and di(C1-C4)alkylamino.
- 45. A composition of claim 44, wherein said phenyl group has from 1 to 3 substituents independently selected from the group consisting of halogen, (C1-C4)haloalkyl, (C1-C4)haloalkoxy, nitro, cyano, and (C1-C4)acyl.
- 46. A composition of claim 37, wherein Ar1 is a substituted or unsubstituted monocyclic or bicyclic heterocycle.
- 47. A composition of claim 46, wherein said heterocycle is selected from the group consisting of pyrrolyl, pyrazolyl, imidazolyl, pyrazinyl, oxazolyl, isoxazolyl, thiazolyl, furyl, thienyl, pyridyl, pyrimidyl, benzothiazolyl, benzoxadiazolyl, purinyl, benzimidazolyl, indolyl, isoquinolyl, quinoxalinyl and quinolyl.
- 48. A composition of claim 47, wherein said heterocycle is selected from the group consisting of thienyl, thiazolyl and benzoxadiazolyl.
- 49. A composition of claim 37, wherein said compound is selected from the group consisting of
- 50. A method for modulating CCR4 function in a cell, comprising contacting said cell with a CCR4-modulating amount of a composition of claim 37.
- 51. A method for modulating CCR4 function, in which said cell is contacted with a CCR4 protein with a therapeutically effective amount of the composition of claim 37.
CROSS-REFERENCES TO RELATED APPLICATIONS
[0001] This application claims the benefit of Provisional Application Ser. No. 60/240,022, filed Oct. 11, 2000, the disclosure of which is incorporated herein by reference.
Provisional Applications (1)
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Number |
Date |
Country |
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60240022 |
Oct 2000 |
US |