Claims
- 1. A pharmaceutical composition useful in treating heart transplant rejection in mammals, which composition comprises one or more pharmaceutically acceptable excipients, a therapeutically effective amount of a non-peptide CCR1 receptor antagonist and a sub-nephrotoxic amount of cyclosporin A.
- 2. The pharmaceutical composition of claim 1 wherein the non-peptide CCR1 receptor antagonist is a compound selected from formula (I):
- 3. The pharmaceutical composition of claim 2 wherein the non-peptide CCR1 receptor antagonist is selected from the group consisting of:
(2R,5S)-1-((4-chloro-2-(aminocarbonyl)phenoxy)methyl)carbonyl-2, 5-dimethyl-4-(4-fluorobenzyl)piperazine; (trans)-1-((4-chloro-2-(glycinamido)phenoxy)methyl)carbonyl-2, 5-dimethyl-4-(4-fluorobenzyl)piperazine; (2R)-1-((4-chloro-2-(ureido)phenoxy)methyl)carbonyl-2-methyl-4-(4-fluorobenzyl)piperazine; (trans)-1-((4-chloro-2-(ureido)phenoxy)methyl)carbonyl-2,5-dimethyl-4-(4-fluorobenzyl)piperazine; (2R,5S)-1-((4-chloro-2-(ureido)phenoxy)methyl) carbonyl-2,5-dimethyl-4-(4-fluorobenzyl)piperazine
and (2R, 5S)-1-((4-chloro-2-(glycinamido)phenoxy)methyl)carbonyl-2, 5-dimethyl-4-(4-fluorobenzyl)piperazine.
- 4. The pharmaceutical composition of claim 2 wherein the non-peptide CCR1 receptor antagonist is (2R)-1-((4-chloro-2-(ureido) phenoxy)methyl)carbonyl-2-methyl-4-(4-fluorobenzyl)piperazine.
- 5. The pharmaceutical composition of claim 4 wherein the mammal in need thereof is a human.
- 6. A method of administering to a mammal in need thereof a pharmaceutical composition useful in treating heart transplant rejection in mammals, which composition comprises a one or more pharmaceutically acceptable excipients, a therapeutically effective amount of a non-peptide CCR1 receptor antagonist and a sub-nephrotoxic amount of cyclosporin A.
- 7. The method of claim 6 wherein the non-peptide CCR1 receptor antagonist and the cyclosporin A are administered to the mammal in need thereof simultaneously or sequentially.
- 8. The method of claim 7 wherein the non-peptide CCR1 receptor antagonist is a compound selected from formula (I):
- 9. The method of claim 8 wherein the non-peptide CCR1 receptor antagonist is selected from the group consisting of:
(2R,5S)-1-((4-chloro-2-(aminocarbonyl)phenoxy)methyl)carbonyl-2, 5-dimethyl-4-(4-fluorobenzyl)piperazine; (trans)-1-((4-chloro-2-(glycinamido)phenoxy)methyl)carbonyl-2, 5-dimethyl-4-(4-fluorobenzyl)piperazine; (2R)-1-((4-chloro-2-(ureido)phenoxy)methyl)carbonyl-2-methyl-4-(4-fluorobenzyl)piperazine; (trans)-1-((4-chloro-2-(ureido)phenoxy)methyl)carbonyl-2,5-dimethyl-4-(4-fluorobenzyl)piperazine; (2R,5S)-1-((4-chloro-2-(ureido) phenoxy)methyl)carbonyl-2,5-dimethyl-4-(4-fluorobenzyl)piperazine
and (2R,5S)- 1-((4-chloro-2-(glycinamido)phenoxy)methyl)carbonyl-2, 5-dimethyl-4-(4-fluorobenzyl)piperazine.
- 10. The method of claim 8 wherein the non-peptide CCR1 receptor antagonist is (2R)-1 -((4-chloro-2-(ureido)phenoxy)methyl)carbonyl-2-methyl-4-(4-fluorobenzyl)piperazine.
- 11. The method of claim 8 wherein the mammal in need thereof is a human.
- 12. A method of treating heart transplant rejection in a mammal which method comprises administering to a mammal in need thereof a pharmaceutical composition comprising one or more pharmaceutically acceptable excipients, a therapeutically effective amount of a non-peptide CCR1 receptor antagonist and a sub-nephrotoxic amount of cyclosporin A.
- 13. The method of claim 12 wherein the non-peptide CCR1 receptor antagonist is a compound selected from formula (I):
- 14. The method of claim 13 wherein the non-peptide CCR1 receptor antagonist is selected from the group consisting of:
(2R,5S)-1 -((4-chloro-2-(aminocarbonyl)phenoxy)methyl)carbonyl-2, 5-dimethyl-4-(4-fluorobenzyl)piperazine; (trans)-1-((4-chloro-2-(glycinamido)phenoxy)methyl)carbonyl-2, 5-dimethyl-4-(4-fluorobenzyl)piperazine; (2R)-1 -((4-chloro-2-(ureido)phenoxy)methyl)carbonyl-2-methyl-4-(4-fluorobenzyl)piperazine; (trans)-1 -((4-chloro-2-(ureido)phenoxy)methyl)carbonyl-2,5-dimethyl-4-(4-fluorobenzyl)piperazine; (2R,5S)-1 -((4-chloro-2-(ureido) phenoxy)methyl)carbonyl-2,5-dimethyl-4-(4-fluorobenzyl)piperazine
and (2R,5S)-1 -((4-chloro-2-(glycinamido)phenoxy)methyl)carbonyl-2, 5-dimethyl-4-(4-fluorobenzyl)piperazine.
- 15. The method of claim 13 wherein the non-peptide CCR1 receptor antagonist is (2R)-1 -((4-chloro-2-(ureido)phenoxy)methyl)carbonyl-2-methyl-4-(4-fluorobenzyl)piperazine.
- 16. The method of claim 15 wherein the mammal in need thereof is a human.
- 17. The method of claim 15 wherein the non-peptide CCR1 receptor antagonist and the cyclosporin A are administered to the mammal in need thereof simultaneously or sequentially.
Parent Case Info
[0001] This is a non-provisional application claiming priority under 35 U.S.C § 119 provisional application Nos. 601222,053, filed Jul. 31, 2000, and 60/231,282, filed Sep. 8, 2000.
Provisional Applications (2)
|
Number |
Date |
Country |
|
60222053 |
Jul 2000 |
US |
|
60231282 |
Sep 2000 |
US |