3-cycloalkylaminopyrrolidine derivatives as modulators of chemokine receptors
The present invention relates to 3-cycloalkylaminopyrrolidine derivatives of the formula I: (wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , X, Y and Z are as defined herein) which are useful as modulators of chemokine receptor activity. In particular, these compounds are useful as modulators of chemokine receptors and more specifically as modulators of the CCR2 and/or CCR5 receptor. The compounds and compositions of the invention may bind to chemokine receptors, e.g., the CCR2 and/or CCR5 chemokine receptors, and are useful for treating diseases associated with chemokine, e.g., CCR2 and/or CCR5, activity, such as atherosclerosis, restenosis, lupus, organ transplant rejection and rheumatoid arthritis.
1. A compound of the formula I:
or pharmaceutically acceptable salt thereof, wherein:
X and Y together are selected from the group consisting of:
a) —CH 2 —NH—(C═O)—;
b) —CH 2 —O—CH 2 —;
Z is a phenyl, pyridyl or pyrimidinyl group that is substituted with a CF 3 group;
R 1 is phenyl, pyridyl, thiazole, pyrimidine or pyrazine, wherein said R 1 is substituted with 0-3 R 1a , wherein R 1a is independently selected from the group consisting of: CH 2 —OMe, alkyl amides, pyrollidinyl amides, morpholinyl, alkyl, alkoxy, CH 2 —NMe 2 , pyridyl, carboxylate, phenyl bearing a CH 2 —OH group, pyrimidine, thiazole, oxazole and pyrazine;
R 2 is OH;
R 3 and R 4 are H;
R 5 is independently selected from the group consisting of hydrogen, alkyl, and formyl;
R 6 and R 7 are each independently selected from the group consisting of H, C 1 -C 10 alkyl, OH, CH 2 —OMe and hydroxyalkyl; and
r=1.
2. A composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier.