Methods and compositions for targeting Tregs using CCR8 inhibitors
The present invention provides compounds of Formula (I) which can be used as CCR8 inhibitors, which can be used as treatment or prevention of cancer using CCR8 inhibitors targeted tumor specific T regulatory cells.
1 . A method of ameliorating symptoms of a condition characterized by abnormal or unwanted activity of regulatory T cells in a subject suffering therefrom, comprising administering to the subject a therapeutically effective amount of a compound, or a or a pharmaceutically acceptable salt, isotope, stereoisomer, tautomer, solvate, or combination thereof, wherein the compound is selected from the group consisting of:
2 . A method of ameliorating symptoms of a condition mediated by abnormal or unwanted CCR8/CCL1 axis in a subject suffering therefrom, comprising administering to the subject a therapeutically effective amount of a compound or a or a pharmaceutically acceptable salt, isotope, stereoisomer, tautomer, solvate, or combination thereof, wherein the compound is selected from the group consisting of:
3 . The method according to claim 2 , wherein the condition is selected from the group consisting of cancer.
4 . The method of claim 3 , wherein the cancer comprises leukemia.
5 . The method of claim 4 , wherein the leukemia comprises chronic lymphocytic leukemia, chronic myeloid leukemia, acute myeloid leukemia, acute lymphoblastic leukemia and leukemic phase of lymphoma.
6 . The method of claim 3 , wherein the cancer comprises a solid tumor.
7 . The method of claim 6 , wherein the solid tumor comprises breast cancer, stomach cancer, colorectal cancer, ovarian cancer, pancreatic cancer and liver cancer.
8 . The method according to claim 2 , wherein the condition is selected from the group consisting of neuropathic pain.
9 . The method of claim 8 , wherein the neuropathic pain is induced by diabetes or spinal cord injury.
10 . A method of ameliorating symptoms of a condition characterized by abnormal or unwanted activity of regulatory T cells in a subject suffering therefrom, comprising administering to the subject a therapeutically effective amount of a compound or a or a pharmaceutically acceptable salt, isotope, stereoisomer, tautomer, solvate, or combination thereof, wherein the compound is:
11 . A method of ameliorating symptoms of a condition characterized by abnormal or unwanted activity of regulatory T cells in a subject suffering therefrom, comprising administering to the subject a therapeutically effective amount of a compound or a or a pharmaceutically acceptable salt, isotope, stereoisomer, tautomer, solvate, or combination thereof, wherein the compound is:
12 . A method of ameliorating symptoms of a condition characterized by abnormal or unwanted activity of regulatory T cells in a subject suffering therefrom, comprising administering to the subject a therapeutically effective amount of a compound or a or a pharmaceutically acceptable salt, isotope, stereoisomer, tautomer, solvate, or combination thereof, wherein the compound is: