(R)-2-methyl-piperazine derivatives as CXCR3 receptor modulators
The invention relates to compounds of Formula (I) wherein R 1 and R 2 are as described in the description; to pharmaceutically acceptable salts thereof, and to the use of such compounds as medicaments, especially as modulators of the CXCR3 receptor.
1. A compound of Formula (I)
wherein
R 1 represents (C 1-4 )alkyl, (C 1-2 )alkoxy-(C 1-2 )alkyl, hydroxy-(C 1-4 )alkyl or —C(O)NH 2 ; and
R 2 represents (C 3-6 )cycloalkyl, (C 1-4 )alkoxy, (C 3-6 )cycloalkoxy or (C 1-2 )fluoroalkyl;
or a salt thereof.
2. The compound according to claim 1 , wherein
R 1 represents (C 1-4 )alkyl, (C 1-2 )alkoxy-(C 1-2 )alkyl or hydroxy-(C 1-4 )alkyl; and
R 2 represents (C 3-6 )cycloalkyl, (C 1-4 )alkoxy or (C 1-2 )fluoroalkyl;
or a salt thereof.
3. The compound according to claim 1 , wherein
R 1 represents ethyl, n-propyl, iso-propyl, tert.-butyl, methoxy-methyl or 1-hydroxy-ethyl; and
R 2 represents cyclopropyl, ethoxy or trifluoromethyl;
or a salt thereof.
4. The compound according to claim 1 , wherein
R 1 represents (C 1-4 )alkyl, (C 1-2 )alkoxy-(C 1-2 )alkyl, hydroxy-(C 1-4 )alkyl or —C(O)NH 2 ; and
R 2 represents (C 1-2 )fluoroalkyl;
or a salt thereof.
5. The compound according to claim 1 , wherein R 1 represents (C 1-4 )alkyl; or a salt thereof.
6. The compound according to claim 1 , wherein R 1 represents ethyl, n-propyl, iso-propyl or tert.-butyl; or a salt thereof.
7. The compound according to claim 1 , wherein R 2 represents (C 3-6 )cycloalkyl; or a salt thereof.
8. The compound according to claim 1 , wherein R 2 represents (C 1-4 )alkoxy; or a salt thereof.
9. The compound according to claim 1 , wherein R 2 represents (C 1-2 )fluoroalkyl; or a salt thereof.
10. The compound according to claim 1 , wherein the compound is:
1-{(R)-4-[4-(2-Ethoxy-pyrimidin-5-yl)-2-trifluoromethyl-thiazol-5-yl]-2-methyl-piperazin-1-yl}-2-(3-isopropyl-[1,2,4]triazol-1-yl)-ethanone;
1-{(R)-4-[4-(2-Ethoxy-pyrimidin-5-yl)-2-trifluoromethyl-thiazol-5-yl]-2-methyl-piperazin-1-yl}-2-(3-ethyl-[1,2,4]triazol-1-yl)-ethanone;
2-(3-tert-Butyl-[1,2,4]triazol-1-yl)-1-{(R)-4-[4-(2-ethoxy-pyrimidin-5-yl)-2-trifluoromethyl-thiazol-5-yl]-2-methyl-piperazin-1-yl}-ethanone;
1-{(R)-4-[4-(2-Ethoxy-pyrimidin-5-yl)-2-trifluoromethyl-thiazol-5-yl]-2-methyl-piperazin-1-yl}-2-(3-methoxymethyl-[1,2,4]triazol-1-yl)-ethanone;
1-(2-{(R)-2-Methyl-4-[2-trifluoromethyl-4-(2-trifluoromethyl-pyrimidin-5-yl)-thiazol-5-yl]-piperazin-1-yl}-2-oxo-ethyl)-1H-[1,2,4]triazole-3-carboxylic acid amide;
2-(3-Ethyl-[1,2,4]triazol-1-yl)-1-{(R)-2-methyl-4-[2-trifluoromethyl-4-(2-trifluoromethyl-pyrimidin-5-yl)-thiazol-5-yl]-piperazin-1-yl}-ethanone;
2-(3-Isopropyl-[1,2,4]triazol-1-yl)-1-{(R)-2-methyl-4-[2-trifluoromethyl-4-(2-trifluoromethyl-pyrimidin-5-yl)-thiazol-5-yl]-piperazin-1-yl}-ethanone;
2-(3-tert-Butyl-[1,2,4]triazol-1-yl)-1-{(R)-2-methyl-4-[2-trifluoromethyl-4-(2-trifluoromethyl-pyrimidin-5-yl)-thiazol-5-yl]-piperazin-1-yl}-ethanone;
2-(3-Methoxymethyl-[1,2,4]triazol-1-yl)-1-{(R)-2-methyl-4-[2-trifluoromethyl-4-(2-trifluoromethyl-pyrimidin-5-yl)-thiazol-5-yl]-piperazin-1-yl}-ethanone;
2-(3-Hydroxymethyl-[1,2,4]triazol-1-yl)-1-{(R)-2-methyl-4-[2-trifluoromethyl-4-(2-trifluoromethyl-pyrimidin-5-yl)-thiazol-5-yl]-piperazin-1-yl}-ethanone;
1-{(R)-2-Methyl-4-[2-trifluoromethyl-4-(2-trifluoromethyl-pyrimidin-5-yl)-thiazol-5-yl]-piperazin-1-yl}-2-(3-propyl-[1,2,4]triazol-1-yl)-ethanone;
2-[3-(1-Hydroxy-ethyl)-[1,2,4]triazol-1-yl]-1-{(R)-2-methyl-4-[2-trifluoromethyl-4-(2-trifluoromethyl-pyrimidin-5-yl)-thiazol-5-yl]-piperazin-1-yl}-ethanone;
2-[3-(1-Hydroxy-1-methyl-ethyl)-[1,2,4]triazol-1-yl]-1-{(R)-2-methyl-4-[2-trifluoromethyl-4-(2-trifluoromethyl-pyrimidin-5-yl)-thiazol-5-yl]-piperazin-1-yl}-ethanone;
1-{(R)-4-[4-(2-Cyclobutoxy-pyrimidin-5-yl)-2-trifluoromethyl-thiazol-5-yl]-2-methyl-piperazin-1-yl}-2-(3-isopropyl-[1,2,4]triazol-1-yl)-ethanone;
1-{(R)-4-[4-(2-Cyclopropyl-pyrimidin-5-yl)-2-trifluoromethyl-thiazol-5-yl]-2-methyl-piperazin-1-yl}-2-(3-ethyl-[1,2,4]triazol-1-yl)-ethanone;
1-{(R)-4-[4-(2-Cyclopropyl-pyrimidin-5-yl)-2-trifluoromethyl-thiazol-5-yl]-2-methyl-piperazin-1-yl}-2-(3-isopropyl-[1,2,4]triazol-1-yl)-ethanone;
2-(3-tert-Butyl-[1,2,4]triazol-1-yl)-1-{(R)-4-[4-(2-cyclopropyl-pyrimidin-5-yl)-2-trifluoromethyl-thiazol-5-yl]-2-methyl-piperazin-1-yl}-ethanone;
1-{(R)-4-[4-(2-Cyclopropyl-pyrimidin-5-yl)-2-trifluoromethyl-thiazol-5-yl]-2-methyl-piperazin-1-yl}-2-(3-methoxymethyl-[1,2,4]triazol-1-yl)-ethanone;
1-{(R)-4-[4-(2-Ethoxy-pyrimidin-5-yl)-2-trifluoromethyl-thiazol-5-yl]-2-methyl-piperazin-1-yl}-2-(3-methyl-[1,2,4]triazol-1-yl)-ethanone;
2-(3-Methyl-[1,2,4]triazol-1-yl)-1-{(R)-2-methyl-4-[2-trifluoromethyl-4-(2-trifluoromethyl-pyrimidin-5-yl)-thiazol-5-yl]-piperazin-1-yl}-ethanone; or
1-{(R)-4-[4-(2-Cyclopropyl-pyrimidin-5-yl)-2-trifluoromethyl-thiazol-5-yl]-2-methyl-piperazin-1-yl}-2-(3-methyl-[1,2,4]triazol-1-yl)-ethanone;
or a salt thereof.
11. A pharmaceutical composition comprising, as active principle, the compound according to claim 1 , or a pharmaceutically acceptable salt thereof, and at least one therapeutically inert excipient.
12. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, formulated as a medicament.
13. A method of treating a disease comprising administering to a patient in need thereof an effective amount of a compound according to claim 1 , wherein the disease is an autoimmune disorder, an inflammatory disease, an infectious disease, a transplant rejection, fibrosis, a neurodegenerative disorder or a cancer.
14. A method of treating a disease comprising administering to a patient in need thereof an effective amount of a compound according to claim 11 , wherein the disease is an autoimmune disorder, an inflammatory disease, an infectious disease, a transplant rejection, fibrosis, a neurodegenerative disorder or a cancer.