Claims
- 1. A compound of Formula (I):
- 2. A compound represented by Formula (Ia):
- 3. The compound of claim 2 wherein R1 is hydrogen, alkyl, acyl, or —SO2Ra where Ra is alkyl.
- 4. The compound of claim 4 wherein R1 is hydrogen, methyl, acetyl, —COCH2CO2H, —COCH2CO2CH3, or —CO2-tert-butyl.
- 5. The compound of claim 2 wherein Y is —SCH2—, —OCH2— or —NHCH2—.
- 6. The compound of claim 5 wherein X is —CONH—.
- 7. The compound of claim 6 wherein Y is —SCH2—.
- 8. The compound of claim 6 wherein Y is —OCH2—.
- 9. The compound of claim 8 wherein alk1 and alk2 are independently an alkylene chain of 1 or 2 carbon atoms.
- 10. The compound of claim 2 wherein Ar1 is a heteroaryl group.
- 11. The compound of claim 3 wherein Ar1 is pyrimidin-2-yl.
- 12. The compound of claim 11 wherein Y is —SCH2— or —OCH2—.
- 13. The compound of claim 12 wherein Ar2 is aryl optionally substituted with one or two substituents selected from the group consisting of alkoxy, hydroxy, or halo.
- 14. The compound of claim 13 wherein Ar2 is phenyl or 3,4-dimethoxyphenyl and is at the 5-position of the pyrimidin-2-yl.
- 15. The compound of claim 12 wherein alk2 is —CH2— and Ar3 is aryl.
- 16. The compound of claim 15 wherein Ar3 is 3,4-dichlorophenyl.
- 17. A compound represented by Formula (Ib):
- 18. The compound of claim 17 wherein Ar1 is a heteroaryl group and Ar2 is aryl optionally substituted with one or two substituents selected from the group consisting of alkoxy, hydroxy, or halo.
- 19. The compound of claim 18 wherein Ar1 is pyrimidin-2-yl and Ar2 is phenyl or 3,4-dimethoxyphenyl and is at the 5-position of the pyrimidin-2-yl.
- 20. The compound of claim 19 wherein X is —CONH— and R1 is —COCH2CO2H, —COCH2CO2CH3, or —CO2-tert-butyl.
- 21. The compound of claim 20 wherein Y and alk1 are independently methylene or ethylene, alk2 is methylene and Ar3 is 3,4-dichlorophenyl.
- 22. An intermediate of the Formula (II):
- 23. The intermediate of claim 22 wherein R11 and R12 are alkoxy.
- 24. The intermediate of claim 22 wherein R11 and R12 are methoxy and are at the 3 and 4 position of the phenyl ring.
- 25. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claims 1-21 and a pharmaceutically acceptable excipient.
- 26. A method of treatment of a disease in a mammal treatable by administration of a CCR-3 receptor antagonist, comprising administration of a pharmaceutical composition comprising a therapeutically effective amount of a compound of claims 1-21 and a pharmaceutically acceptable excipient.
- 27. The method of claim 26 wherein the disease is asthma.
- 28. A process for preparing a compound as claimed in claim 1, which process comprises:
coupling a compound having a formula 7, 22wherein Pro is a protective group, and alk2 and Ar3 are as defined in claim 1;with a compound of formula 8: Ar1—Ar2—Y—CO2H 8wherein Ar1, Ar2 and Y are as described in claim 1;removal of the protecting group to provide a compound of Formula (I) 23wherein R1 is hydrogen, and Ar1, Ar2, alk2 and Ar3 are as defined in claim 1; and conversion to compounds of Formula (I) wherein R1 is acyl or sulfonyl with an acid halide of general formula R1C(O)Hal or a sulfonyl halide of general formula R1SO2Hal, wherein Hal is a halo group.
- 29. A process for preparing a compound as claimed in claim 1, which process comprises
reduction of the cyano group of a compound having a formula 10: 24wherein Pro is a protective group, and alk2 and Ar3 are as defined in claim 1;coupling with a compound of Formula 8: Ar1—Ar2—Y—CO2H 8wherein Ar1, Ar2 and Y are as described in claim 1;removal of the protecting group to provide a compound of Formula (I): 25wherein R1 is hydrogen, and Ar1, Ar2, alk2 and Ar3 are as defined in claim 1, and conversion to compounds of Formula (I) wherein R1 is an acyl or sulfonyl group with an acid halide R1C(O)Hal or a sulfonyl halide R1SO2Hal, wherein Hal is a halo group.
- 30. A process for preparing a compound as claimed in claim 1, which process comprises coupling a compound having a formula 15a or 15b
- 31. A process for preparing a compound as claimed in claim 1, which process comprises
mesylating a compound having a formula 16, 28wherein R1 is alkyl, and alk2 and Ar3 are as defined in claim 1;converting to a cyanide followed by reduction, and coupling with a compound of formula 8Ar1—Ar2—Y—CO2H 8wherein Ar1, Ar2 and Y are as described in claim 1, to provide a compound of Formula (I) 29wherein R1 is alkyl, and Ar1, Ar2, alk2, Ar3, and Y are as described in claim 1.
CROSS REFERENCE TO RELATED APPLICATION
[0001] This application claims benefit under Title 35 U.S.C. 119 (e) of U.S. Provisional Application No.60/256,585 filed Dec. 19, 2000.
Provisional Applications (1)
|
Number |
Date |
Country |
|
60256585 |
Dec 2000 |
US |
Divisions (1)
|
Number |
Date |
Country |
Parent |
10034034 |
Dec 2001 |
US |
Child |
10368097 |
Feb 2003 |
US |