Claims
- 1. A method of inhibiting effective binding of a chemokine to its cellular receptor, comprising contacting a cellular population with an effective amount of a compound having the following structure:
- 2. The method of claim 1, wherein said cellular population comprises immune system cells.
- 3. The method of claim 1, wherein R1, R5, R6, and R10 are H, R2 and R7 are chlorine, R11 is CH(CH3)(CH2)3CH(CH3)2, R12 and R13 are methyl, and X is C═CH(CH2)2.
- 4. The method of claim 3, wherein R3 and R9 are hydroxy, and R4 and R9 are COOH or a salt thereof.
- 5. The method of claim 3, wherein R3 and R8 are O(CH2)n—R26—R27, where n is 1, R26 is phenyl, R27 is selected from the group consisting of aryl, nitro, COOH or a salt thereof, B(OH)2 or a salt thereof, C1-C7 alkoxy, and combinations thereof, where the aryl of R27 is optionally substituted with nitro, COOH or a salt thereof, B(OH)2 or a salt thereof, C1-C7 alkoxy, or combinations thereof.
- 6. The method of claim 1, wherein R3 and R9 are hydroxy, and R4 and R9 are C(O)NHCH(R28)COOH, where R28 is H, CH2CH(CH3)2, CH2Ph, CH2COOH or a salt thereof, or CH2CH2COOH or a salt thereof.
- 7. The method of claim 1, wherein said chemokine is selected from the group consisting of a class CXC chemokine and a class CC chemokine.
- 8. The method of claim 1, wherein said class CC chemokine is RANTES.
- 9. The method of claim 7, wherein said class CC chemokine is selected from the group consisting of RANTES, MCP-1, MCP-2, MCP-3, MCP-4, eotaxin, MDC, TARC, and HCC-1.
- 10. The method of claim 7, wherein said class CXC chemokine is selected from the group consisting of PF4, IL-8, GRO-alpha, ENA-78, IP-10, BCA-1, ITAC, and SDF-1.
- 11. The method of claim 1, wherein chemokine-induced cellular chemotaxis is inhibited.
- 12. A method of treating an inflammatory disease, comprising administering to a patient a therapeutically effective amount of a compound having the following formula:
- 13. The method of claim 12, wherein said cellular population comprises immune system cells.
- 14. The method of claim 12, wherein R1, R5, R6, and R10 are H, R2 and R7 are chlorine, R11 is CH(CH3)(CH2)3CH(CH3)2, R12 and R13 are methyl, and X is C═CH(CH2)2.
- 15. The method of claim 14, wherein R3 and R8 are hydroxy, and R4 and R9 are COOH or a salt thereof.
- 16. The method of claim 14, wherein R3 and R8 are O(CH2)n—R26—R27, where n is 1, R26 is phenyl, R27 is selected from the group consisting of aryl, nitro, COOH or a salt thereof, B(OH)2 or a salt thereof, C1-C7 alkoxy, and combinations thereof, where the aryl of R27 is optionally substituted with nitro, COOH or a salt thereof, B(OH)2 or a salt thereof, C1-C7 alkoxy, or combinations thereof.
- 17. The method of claim 14, wherein R3 and R8 are hydroxy, and R4 and R9 are C(O)NHCH(R28)COOH, where R28 is H, CH2CH(CH3)2, CH2Ph, CH2COOH or a salt thereof, or CH2CH2COOH or a salt thereof.
- 18. The method of claim 12, wherein said chemokine is selected from the group consisting of a class CXC chemokine and a class CC chemokine.
- 19. The method of claim 18, wherein said class CC chemokine is RANTES.
- 20. The method of claim 18, wherein said class CC chemokine is selected from the group consisting of RANTES, MCP-1, MCP-2, MCP-3, MCP-4, eotaxin, MDC, TARC, and HCC-1.
- 21. The method of claim 18, wherein said class CXC chemokine is selected from the group consisting of PF4, IL-8, GRO-alpha, ENA-78, IP-10, BCA-1, ITAC, and SDF-1.
- 22. A compound having the formula:
- 23 The compound of claim 22, wherein at least one of R4 and R9 is C(O)NHCH(R28)COOR29, where R28 is an amino acid side chain and R29 is H or a C1-C4 alkyl.
- 24. The compound of claim 23, wherein R1, R5, R6, and R10 are H, R2 and R7 are chlorine, R11 is CH(CH3)(CH2)3CH(CH3)2, R12 and R13 are methyl, and X is C═CH(CH2)2.
- 25. The compound of claim 24, wherein R3 and R8 are hydroxy, and R4 and R9 are C(O)NHCH(R28)COOH, where R28 is H, CH2CH(CH3)2, CH2Ph, CH2COOH or a salt thereof, and CH2CH2COOH or a salt thereof.
- 26. The compound of claim 22, wherein at least one of R3 and R8 is O(CH2)n—R26—R27, where n is 1 to 7, R26 is aryl, R27 is COOH or a salt thereof, B(OH)2 or a salt thereof, nitro, C1-C7 alkoxy, or aryl where the aryl of R27 is substituted with COOH or a salt thereof, B(OH)2 or a salt thereof, nitro, or C1-C7 alkoxy.
- 27. The compound of claim 26, wherein R1, R5, R6, and R10 are H, R2 and R7 are chlorine, R11 is CH(CH3)(CH2)3CH(CH3)2, R12 and R13 are methyl, and X is C═CH(CH2)2.
- 28. The compound of claim 27, wherein R3 and R9 are O(CH2)n—R26—R27, where n is 1, R26 is phenyl, R27 is selected from the group consisting of aryl, nitro, COOH or a salt thereof, B(OH)2 or a salt thereof, C1-C7 alkoxy, and combinations thereof, where the aryl of R27 is optionally substituted with nitro, COOH or a salt thereof, B(OH)2 or a salt thereof, C1-C7 alkoxy, or combinations thereof.
- 29. A pharmaceutical composition comprising a compound according to claim 22 and a pharmaceutically acceptable carrier, excipient, or diluent therefor.
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] The present application claims the benefit of provisional patent application Serial No. 60/167,864, filed on Nov. 29, 1999, which is hereby incorporated by reference in its entirety.
Government Interests
[0002] This invention was made with government support under grant number Al 36624 and contract number NO1-CO-56000 awarded by the National Institutes of Health. The Government has certain rights in the invention.
Divisions (1)
|
Number |
Date |
Country |
Parent |
09771769 |
Jan 2001 |
US |
Child |
10436845 |
May 2003 |
US |