Claims
- 1. An assay for identifying a compound useful for blocking CMV dissemination is a host, comprising the step of determining whether said compound inhibits the binding of a chemokine to US28 or a US28 fragment.
- 2. An assay in accordance with claim 1, wherein said chemokine is selected from the group consisting of fractalkine, MIP-1α, MIP-1β, MCP-1 and RANTES.
- 3. An assay in accordance with claim 1, wherein said chemokine is fractalkine.
- 4. An assay in accordance with claim 1, wherein said step of determining comprises specifically binding labeled fractalkine to the ligand binding domain of US28.
- 5. A method for preventing dissemination of CMV in a human, comprising administering an effective amount of a compound which blocks the binding of a chemokine to US28 or a US28 fragment.
- 6. A method in accordance with claim 5, wherein said compound was identified by the assay of claim 1.
- 7. A method in accordance with claim 5, wherein said compound has the formula:
- 8. A method in accordance with claim 7, wherein X1, X3, X4, Y1, Y2, Y3 and Y4 are all CH; Z2 is —S—, and NHet is a substituted 6-membered nitrogen heterocycle.
- 9. A method in accordance with claim 5, wherein said compound has the formula:
- 10. A method in accordance with claim 9, wherein m is 0 and n is 1.
- 11. A method in accordance with claim 9, wherein m is 0, n is 1 and R2 is selected from the group consisting of halogen, (C1-C4)alkyl, (C1-C4)alkoxy, (C1-C4)alkylthio and (C1-C4)haloalkyl.
- 12. A method in accordance with claim 9, wherein m is 0, n is 1 and R2 is selected from the group consisting of halogen and (C1-C4)alkylthio.
- 13. A method in accordance with claim 5, wherein said compound is selected from the group consisting of methiothepin, octoclothepin and pharmaceutically acceptable salts thereof.
- 14. A method for reducing cell motility in a CMV-infected cell, said method comprising contacting said CMV-infected cell with a motility-reducing amount of a compound that inhibits chemokine binding to US28 on the surface of said infected cell.
- 15. A method in accordance with claim 14, wherein said chemokine is a member selected from the group consisting of fractalkine, MIP-1α, MIP-1β, MCP-1 and RANTES.
- 16. A method in accordance with claim 14, wherein said chemokine is fractalkine.
- 17. A method in accordance with claim 14, wherein said compound has the formula:
- 18. A method in accordance with claim 17, wherein m is 0 and n is 1.
- 19. A method in accordance with claim 17, wherein m is 0, n is 1 and R2 is selected from the group consisting of halogen, (C1-C4)alkyl, (C1-C4)alkoxy, (C1-C4)alkylthio and (C1-C4)haloalkyl.
- 20. A method in accordance with claim 17, wherein m is 0, n is 1 and R2 is selected from the group consisting of halogen and (C1-C4)alkylthio.
- 21. A method in accordance with claim 14, wherein said compound is selected from the group consisting of methiothepin, octoclothepin and pharmaceutically acceptable salts thereof.
- 22. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound of the formula:
- 23. A composition in accordance with claim 22, wherein X1, X3, X4, Y1, Y2, Y3 and Y4 are all CH; Z2 is —S—, and NHet is a substituted 6-membered nitrogen heterocycle.
- 24. A composition in accordance with claim 22, wherein said compound has the formula:
- 25. A composition in accordance with claim 24, wherein m is 0 and n is 1.
- 26. A composition in accordance with claim 24, wherein m is 0, n is 1 and R2 is selected from the group consisting of halogen, (C1-C4)alkyl, (C1-C4)alkoxy, (C1-C4)haloalkyl and (C1-C4)alkylthio.
- 27. A composition in accordance with claim 24, wherein m is 0, n is 1 and R2 is selected from the group consisting of halogen and (C1-C4)alkylthio.
- 28. A composition in accordance with claim 24, wherein said compound is selected from the group consisting of methiothepin, octoclothepin and pharmaceutically acceptable salts thereof.
CROSS-REFERENCES TO RELATED APPLICATIONS
[0001] This application claims the benefit of U.S. Provisional Patent Application Serial No. 60/228,974, filed Aug. 30, 2000, and U.S. Provisional Patent Application Serial No. ______, filed Aug. 30, 2001, entitled “Bicyclic Compounds as Inhibitors of Chemokine Binding to US 28” (Attorney Docket No. 019934-001000US), the disclosures of each being incorporated herein by reference. Related subject matter is described in co-owned applications Ser. No. ______, filed Aug. 30, 2001, entitled “Reagents and Methods for the Diagnosis of CMV Dissemination” (Attorney Docket No. 019934-000910US/PCT) which claims the benefit of Ser. No. 60/229,191 filed Aug. 30, 2000; and in Ser. No. ______, filed Aug. 30, 2001, entitled “Inhibition of CMV Infection and Dissemination” (Attorney Docket No. 019934-002510US/PCT) which claims the benefit of Ser. No. 60/229,365, filed Aug. 30, 2000, the disclosures of each being incorporated herein by reference.
Provisional Applications (3)
|
Number |
Date |
Country |
|
60228974 |
Aug 2000 |
US |
|
60229191 |
Aug 2000 |
US |
|
60229365 |
Aug 2000 |
US |