1,2,4-triazine-3-amine derivative, preparation method therefor, and use thereof in medicine

Abstract

A 1,2,4-triazine-3-amine derivative, a preparation therefor, and use thereof in medicine are provided. Specifically, a 1,2,4-triazine-3-amine derivative as represented by general formula (I), a preparation method therefor, a pharmaceutical composition containing the derivative, and use thereof as a therapeutic agent, in particular as an A2a or A2b receptor antagonist, and use thereof in the preparation of a medicament for treating a condition or disorder that is ameliorated by means of inhibition of the A2a or A2b receptor are provided. Each substituent in general formula (I) is defined in the description.

What is claimed is: 
     
         1 . A compound selected from the group consisting of 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         2 . The compound according to  claim 1 , selected from the group consisting of: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         3 . A compound selected from the group consisting of: 
       
         
           
           
               
               
           
         
       
       and 3 or a pharmaceutically acceptable salt thereof. 
     
     
         4 . The compound according to  claim 3 , selected from the group consisting of: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         5 . The compound according to  claim 3 , selected from the group consisting of 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         6 . A pharmaceutical composition, comprising the compound according to  claim 1 , and one or more pharmaceutically acceptable carriers, diluents or excipients. 
     
     
         7 . A pharmaceutical composition, comprising the compound according to  claim 3 , and one or more pharmaceutically acceptable carriers, diluents or excipients. 
     
     
         8 . A method for treating a disease or condition in a subject, the method comprising administering to the subject the compound according to  claim 1 , wherein the disease or condition is selected from the group consisting of cancer, depression, Parkinson's disease, Huntington's disease, Alzheimer's disease, abnormal movement disorder, sleep disorder, wherein the cancer is selected from the group consisting of melanoma, brain tumor, esophageal cancer, stomach cancer, liver cancer, pancreatic cancer, colorectal cancer, lung cancer, kidney cancer, breast cancer, ovarian cancer, prostate cancer, skin cancer, neuroblastoma, sarcoma, osteochondroma, osteoma, osteosarcoma, seminoma, testicular tumor, uterine cancer, head and neck cancer, multiple myeloma, malignant lymphoma, polycythemia vera, leukemia, thyroid tumor, ureteral tumor, bladder tumor, gallbladder cancer, cholangiocarcinoma, chorionic epithelioma and pediatric tumor. 
     
     
         9 . A method for treating a disease or condition in a subject, the method comprising administering to the subject the compound according to  claim 3 , wherein the disease or condition is selected from the group consisting of cancer, depression, Parkinson's disease, Huntington's disease, Alzheimer's disease, abnormal movement disorder, sleep disorder, wherein the cancer is selected from the group consisting of melanoma, brain tumor, esophageal cancer, stomach cancer, liver cancer, pancreatic cancer, colorectal cancer, lung cancer, kidney cancer, breast cancer, ovarian cancer, prostate cancer, skin cancer, neuroblastoma, sarcoma, osteochondroma, osteoma, osteosarcoma, seminoma, testicular tumor, uterine cancer, head and neck cancer, multiple myeloma, malignant lymphoma, polycythemia vera, leukemia, thyroid tumor, ureteral tumor, bladder tumor, gallbladder cancer, cholangiocarcinoma, chorionic epithelioma and pediatric tumor. 
     
     
         10 . A method for treating a disease or condition ameliorated by inhibition of A 2a  and/or A 2b  receptor in a subject, the method comprising administering to the subject the compound according to  claim 1 , wherein the disease or condition is selected from the group consisting of cancer, depression, Parkinson's disease, Huntington's disease, Alzheimer's disease, abnormal movement disorder, sleep disorder, wherein the cancer is selected from the group consisting of melanoma, brain tumor, esophageal cancer, stomach cancer, liver cancer, pancreatic cancer, colorectal cancer, lung cancer, kidney cancer, breast cancer, ovarian cancer, prostate cancer, skin cancer, neuroblastoma, sarcoma, osteochondroma, osteoma, osteosarcoma, seminoma, testicular tumor, uterine cancer, head and neck cancer, multiple myeloma, malignant lymphoma, polycythemia vera, leukemia, thyroid tumor, ureteral tumor, bladder tumor, gallbladder cancer, cholangiocarcinoma, chorionic epithelioma and pediatric tumor. 
     
     
         11 . A method for treating a disease or condition ameliorated by inhibition of A 2a  and/or A 2b  receptor in a subject, the method comprising administering to the subject the compound according to  claim 3 , wherein the disease or condition is selected from the group consisting of cancer, depression, Parkinson's disease, Huntington's disease, Alzheimer's disease, abnormal movement disorder, sleep disorder, wherein the cancer is selected from the group consisting of melanoma, brain tumor, esophageal cancer, stomach cancer, liver cancer, pancreatic cancer, colorectal cancer, lung cancer, kidney cancer, breast cancer, ovarian cancer, prostate cancer, skin cancer, neuroblastoma, sarcoma, osteochondroma, osteoma, osteosarcoma, seminoma, testicular tumor, uterine cancer, head and neck cancer, multiple myeloma, malignant lymphoma, polycythemia vera, leukemia, thyroid tumor, ureteral tumor, bladder tumor, gallbladder cancer, cholangiocarcinoma, chorionic epithelioma and pediatric tumor. 
     
     
         12 . A method for treating a disease or condition in a subject, the method comprising administering to the subject the pharmaceutical composition according to  claim 6 , wherein the disease or condition is selected from the group consisting of cancer, depression, Parkinson's disease, Huntington's disease, Alzheimer's disease, abnormal movement disorder, sleep disorder, wherein the cancer is selected from the group consisting of melanoma, brain tumor, esophageal cancer, stomach cancer, liver cancer, pancreatic cancer, colorectal cancer, lung cancer, kidney cancer, breast cancer, ovarian cancer, prostate cancer, skin cancer, neuroblastoma, sarcoma, osteochondroma, osteoma, osteosarcoma, seminoma, testicular tumor, uterine cancer, head and neck cancer, multiple myeloma, malignant lymphoma, polycythemia vera, leukemia, thyroid tumor, ureteral tumor, bladder tumor, gallbladder cancer, cholangiocarcinoma, chorionic epithelioma and pediatric tumor. 
     
     
         13 . A method for treating a disease or condition in a subject, the method comprising administering to the subject the pharmaceutical composition according to  claim 7 , wherein the disease or condition is selected from the group consisting of cancer, depression, Parkinson's disease, Huntington's disease, Alzheimer's disease, abnormal movement disorder, sleep disorder, wherein the cancer is selected from the group consisting of melanoma, brain tumor, esophageal cancer, stomach cancer, liver cancer, pancreatic cancer, colorectal cancer, lung cancer, kidney cancer, breast cancer, ovarian cancer, prostate cancer, skin cancer, neuroblastoma, sarcoma, osteochondroma, osteoma, osteosarcoma, seminoma, testicular tumor, uterine cancer, head and neck cancer, multiple myeloma, malignant lymphoma, polycythemia vera, leukemia, thyroid tumor, ureteral tumor, bladder tumor, gallbladder cancer, cholangiocarcinoma, chorionic epithelioma and pediatric tumor. 
     
     
         14 . A method for treating a disease or condition ameliorated by inhibition of A 2a  and/or A 2b  receptor in a subject, the method comprising administering to the subject the pharmaceutical composition according to  claim 6 , wherein the disease or condition is selected from the group consisting of cancer, depression, Parkinson's disease, Huntington's disease, Alzheimer's disease, abnormal movement disorder, sleep disorder, wherein the cancer is selected from the group consisting of melanoma, brain tumor, esophageal cancer, stomach cancer, liver cancer, pancreatic cancer, colorectal cancer, lung cancer, kidney cancer, breast cancer, ovarian cancer, prostate cancer, skin cancer, neuroblastoma, sarcoma, osteochondroma, osteoma, osteosarcoma, seminoma, testicular tumor, uterine cancer, head and neck cancer, multiple myeloma, malignant lymphoma, polycythemia vera, leukemia, thyroid tumor, ureteral tumor, bladder tumor, gallbladder cancer, cholangiocarcinoma, chorionic epithelioma and pediatric tumor. 
     
     
         15 . A method for treating a disease or condition ameliorated by inhibition of A 2a  and/or A 2b  receptor in a subject, the method comprising administering to the subject the pharmaceutical composition according to  claim 7 , wherein the disease or condition is selected from the group consisting of cancer, depression, Parkinson's disease, Huntington's disease, Alzheimer's disease, abnormal movement disorder, sleep disorder, wherein the cancer is selected from the group consisting of melanoma, brain tumor, esophageal cancer, stomach cancer, liver cancer, pancreatic cancer, colorectal cancer, lung cancer, kidney cancer, breast cancer, ovarian cancer, prostate cancer, skin cancer, neuroblastoma, sarcoma, osteochondroma, osteoma, osteosarcoma, seminoma, testicular tumor, uterine cancer, head and neck cancer, multiple myeloma, malignant lymphoma, polycythemia vera, leukemia, thyroid tumor, ureteral tumor, bladder tumor, gallbladder cancer, cholangiocarcinoma, chorionic epithelioma and pediatric tumor.