Chemokine receptor antagonists and methods of use
Disclosed are novel compounds and a method of treating a disease associated with aberrant leukocyte recruitment and/or activation. The method comprises administering to a subject in need an effective amount of a compound represented by: or physiologically acceptable salt thereof.
1. A method for treating a disease associated with aberrant leukocyte recruitment, aberrant leukocyte activation or aberrant leukocyte recruitment and activation, comprising administering to a subject in need thereof an effective amount of a compound having the formula:
or a physiologically acceptable salt thereof, wherein:
n is one to four;
M is >CR 1 R 2 ;
R 1 is —OH;
R 2 is 4-halophenyl;
R 70 and R 71 are —H, and R 72 and R 73 are —CH 3 ; or
R 70 and R 71 are —CH 3 , and R 72 and R 73 are —H;
Z is
X 1 is —CH 2 O—;
Ring A is unsubstituted;
R 40 is selected from the group consisting of:
wherein the disease is selected from the group consisting of arthritis, atherosclerosis, arteriosclerosis, restenosis, ischemia/reperfusion injury, diabetes mellitus, psoriasis, multiple sclerosis, inflammatory bowel diseases, resection of a transplanted organ or tissue, graft versus host disease, allergy and asthma.
2. The method of claim 1 , wherein R 40 is
3. The method of claim 1 , wherein said 4-halophenyl is selected from the group consisting of 4-chlorophenyl, 4-bromophenyl and 4-fluorophenyl.
4. The method of claim 3 , wherein said 4-halophenyl is 4-chlorophenyl.
5. The method of claim 4 , wherein:
R 70 and R 71 are —H and R 72 and R 73 are —CH 3 ;
n is two; and
the compound has the structure:
6. The method of claim 5 , wherein R 40 is
7. The method of claim 1 , wherein said disease is multiple sclerosis.
8. The method of claim 1 , wherein said disease is arthritis, and said arthritis is rheumatoid arthritis.