[1,2,4]triazolo[1,5-c]pyrimidine derivative as A
Provided are a compound represented by formula (I), an isomer or a pharmaceutically acceptable salt thereof, and an application of the same in preparing a drug for treating a disease related to A 2A receptor. The R 1 , R 2 , R 3 , ring A, ring B, n, and m are as defined in the specification.
1. A compound represented by formula (I), or a pharmaceutically acceptable salt thereof,
wherein
R 1 is selected from the group consisting of H, CN, COOH, and
or is selected from the group consisting of C 1-3 alkyl, C 1-3 alkyl-O—C 1-3 alkyl-, C 1-3 alkyl-C(=O)NH-, and C 3-6 cycloalkyl, each of which is optionally substituted by 1, 2 or 3 R;
R 2 is each independently selected from the group consisting of H, F, Cl, Br, I, OH, NH 2 , and CN, or is independently selected from the group consisting of C 3-6 cycloalkyl, C 1-6 alkyl, and C 1-6 heteroalkyl, each of which is optionally substituted by 1, 2 or 3 R;
R 3 is each independently selected from the group consisting of H, F, Cl, Br, I, OH, NH 2 , and CN, or is independently selected from the group consisting of C 1-6 alkyl or C 1-6 heteroalkyl, each of which is optionally substituted by 1, 2 or 3 R;
n is 0, 1, 2 or 3;
m is 0, 1, 2 or 3;
ring A is selected from the group consisting of 6- to 10-membered aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heterocycloalkyl and 5- to 10-membered heterocycloalkenyl;
ring B is selected from the group consisting of phenyl and 5- to 6-membered heteroaryl;
R is selected from the group consisting of F, Cl, Br, I, OH, NH 2 , and CN, or is selected from the group consisting of C 1-3 alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkyl-NH—, 3- to 6-membered heterocycloalkyl, 3- to 6-membered heterocycloalkyl-O-, and phenyl, each of which is optionally substituted by 1, 2 or 3 R′;
R′ is selected from the group consisting of F, Cl, Br, I, OH, NH 2 , Me, and
the heteroatom or the heteroatom group of the C1-6 heteroalkyl, 5- to 10-membered heteroaryl, 5- to 10-membered heterocycloalkyl, 3- to 6-membered heterocycloalkyl and 5- to 10-membered heterocycloalkenyl is each independently selected from the group consisting of N, O, S, NH, —C(═O)—, —C(═O)O- and —C(═O)NH—;
the number of the heteroatom or the heteroatom group is each independently 1, 2, 3 or 4.
2. The compound, or a pharmaceutically acceptable salt thereof according to claim 1 , wherein R is selected from the group consisting of F, Cl, Br, I, OH, NH 2 , and CN, or is selected from the group consisting of Me, Et,
each of which is optionally substituted by 1, 2 or 3 R′.
3. The compound, or a pharmaceutically acceptable salt thereof according to claim 2 , wherein R is selected from the group consisting of F, Cl, Br, I, OH, NH 2 , CN,
Me, Et,
4. The compound, or a pharmaceutically acceptable salt thereof according to claim 1 , wherein R 1 is selected from the group consisting of H, CN, COOH, and
or is selected from the group consisting of Me, Et,
each of which is optionally substituted by 1, 2 or 3 R.
5. The compound, or a pharmaceutically acceptable salt thereof according to claim 4 , wherein R 1 is selected from the group consisting of H, CN, COOH, Me, Et,
6. The compound, or a pharmaceutically acceptable salt thereof according to claim 1 , wherein R 2 is each independently selected from the group consisting of H, F, Cl, Br, I, OH NH 2 , and CN, or is independently selected from the group consisting of C 3-6 cycloalkyl, C 1-3 alkyl and C 1-3 alkoxy, each of which is optionally substituted by 1, 2 or 3 R.
7. The compound, or a pharmaceutically acceptable salt thereof according to claim 6 , wherein R 2 is each independently selected from the group consisting of H, F, Cl, Br, I, OH, NH 2 , CN, Me, Et, CF 3 ,
8. The compound, or a pharmaceutically acceptable salt thereof according to claim 1 , wherein R 3 is each independently selected from the group consisting of H, F, Cl, Br, I, OH, NH 2 , and CN, or is independently selected from the group consisting of C 1-3 alkyl and C 1-3 alkoxy, each of which is optionally substituted by 1, 2 or 3 R.
9. The compound, or a pharmaceutically acceptable salt thereof according to claim 8 , wherein R 3 is each independently selected from the group consisting of H, F, Cl, Br, I, OH, NH 2 , CN, Me, Et, CF 3 and
10. The compound, or a pharmaceutically acceptable salt thereof according to claim 1 , wherein ring A is selected from the group consisting of phenyl, pyridyl, tetrahydropyranyl, 3,6-dihydro-2H-pyranyl, piperidinyl, 1,2,3,6-tetrahydropyridyl, 1H-indolyl, 1H-indazolyl, 1H-benzo[d]imidazolyl, benzo[d][1,3 dioxolyl, indolin-2-onyl, 1H-benzo[d][1,2,3]triazolyl, quinolinyl and 1,2,3,4-tetrahydroquinolinyl.
11. The compound, or a pharmaceutically acceptable salt thereof according to claim 10 , wherein the moiety
is selected from the group consisting of
12. The compound, or a pharmaceutically acceptable salt thereof according to claim 11 , wherein the moiety
is selected from the group consisting of
13. The compound, or a pharmaceutically acceptable salt thereof according to claim 12 , wherein the moiety
is selected from the group consisting of
14. The compound, or a pharmaceutically acceptable salt thereof according to claim 1 , wherein ring B is selected from the group consisting of phenyl, pyridyl, imidazolyl, pyrazolyl, furyl, thienyl, and thiazolyl.
15. The compound, or a pharmaceutically acceptable salt thereof according to claim 14 , wherein the moiety
is selected from the group consisting of
16. The compound, or a pharmaceutically acceptable salt thereof according to claim 15 , wherein the moiety
is selected from the group consisting of
17. The compound, or a pharmaceutically acceptable salt thereof according to claim 16 , wherein the moiety
is selected from the group consisting of
18. The compound, or a pharmaceutically acceptable salt thereof according to claim 1 , which is selected from the group consisting of
wherein R 1 , R 2 , and R 3 are as defined in claim 1 .
19. The compound or a pharmaceutically acceptable salt thereof according to claim 1 , wherein the compound is selected from the group consisting of
20. A pharmaceutical composition comprising a therapeutically effective amount of a compound, or a pharmaceutically acceptable salt thereof according to claim 1 , and pharmaceutically acceptable carrier(s).
21. The compound, or a pharmaceutically acceptable salt thereof according to claim 1 , wherein the compound is:
22. The compound, or a pharmaceutically acceptable salt thereof according to claim 1 , wherein the compound is:
23. The compound, or a pharmaceutically acceptable salt thereof according to claim 1 , wherein the compound is: