JPWO2020052631A5

JPWO2020052631A5 -

Info

Publication number: JPWO2020052631A5
Application number: JP2021513827A
Authority: JP
Publication date: 2022-09-05

Claims

Formula (I):

[In the formula,
X is selected from amino, halogen, hydroxyl, cyano, C _1-12 alkoxyl, N-(C _1-12 alkyl)amino, N,N-(C _1-12 alkyl) ₂ amino, C _1-12 alkanoylamino is,
Ring A is a 3- to 12-membered saturated or unsaturated monocyclic or polycyclic heterocyclyl, and one or more —CH ₂ — groups on Ring A are —C(O)— or —S( O) optionally replaced by _a- , where a=0, 1 or 2;
Z is hydrogen, halogen, cyano, hydroxyl, amino, carbamoyl, urea, carbamate, C _1-12 alkyl, N-(C _1-12 alkyl)amino, N,N-(C _1-12 alkyl) ₂ amino, 3- to 12-membered saturated or unsaturated carbocyclyl, or 3- to 12-membered saturated or unsaturated heterocyclyl, which is optionally monosubstituted or independently polysubstituted by R ₂ ; One or more —CH ₂ — groups in a 12-membered saturated or unsaturated carbocyclyl or 3- to 12-membered saturated or unsaturated heterocyclyl ring system are —C(O)— or —S(O) _a — and a = 0, 1 or 2, optionally replaced by
Y is -WV, W is a bond, O, S, -NH-, C _1-12 alkylene, C _1-12 alkylene-NH-, V is C _1-12 alkyl, C _1-12 alkoxyl, C _1-12 alkyl-OH, amino, carbamoyl, urea, carbamate, N-(C _1-12 alkyl)amino, N,N-(C _1-12 alkyl) ₂ amino, N-(C _1-12 alkyl)carbamoyl, N,N-(C _1-12 alkyl) ₂ carbamoyl, C _1-12 alkanoylamino, 3-12 membered saturated or unsaturated carbocyclyl, or 3-12 membered saturated or unsaturated heterocyclyl which is optionally monosubstituted or independently polysubstituted by R ₃ and is a 3- to 12-membered saturated or unsaturated carbocyclyl, or a 3- to 12-membered saturated or unsaturated heterocyclyl ring system one or more —CH ₂ — groups in is optionally replaced by —C(O)— or —S(O) _a —, a=0, 1 or 2;
Each R ₁ is halogen, hydroxyl, cyano, amino, carbamoyl, urea, carbamate, C _1-12 alkyl, C _1-12 haloalkyl, C _1-12 alkoxyl, C _1-12 haloalkoxyl, C _1-12 alkyl- OH, N-(C _1-12 alkyl)amino, N,N-(C _1-12 alkyl) ₂ amino, N-(C _1-12 alkyl)carbamoyl, N,N-(C _1-12 alkyl) ₂ independently selected from carbamoyl, C _1-12 alkanoylamino, 3-10 membered saturated or unsaturated carbocyclyl, or 3-10 membered saturated or unsaturated heterocyclyl, said 3-10 membered saturated or unsaturated carbocyclyl; or a 3- to 10-membered saturated or unsaturated heterocyclyl optionally monosubstituted or independently polysubstituted with _R4 ,
Each R ₂ is halogen, hydroxyl, cyano, amino, carbamoyl, urea, carbamate, C _1-12 alkyl, C _1-12 haloalkyl, C _1-12 alkoxyl, C _1-12 haloalkoxyl, C _1-12 alkyl- OH, N-(C _1-12 alkyl)amino, N,N-(C _1-12 alkyl) ₂ amino, N-(C _1-12 alkyl)carbamoyl, N,N-(C _1-12 alkyl) ₂ independently selected from carbamoyl, C _1-12 alkanoylamino, 3-10 membered saturated or unsaturated carbocyclyl, or 3-10 membered saturated or unsaturated heterocyclyl, said 3-10 membered saturated or unsaturated carbocyclyl; or a 3- to 10- _membered saturated or unsaturated heterocyclyl optionally monosubstituted or independently polysubstituted with R5,
Each R ₃ is halogen, hydroxyl, cyano, amino, carbamoyl, urea, carbamate, C _1-12 alkyl, C _1-12 haloalkyl, C _1-12 alkoxyl, C _1-12 haloalkoxyl, C _1-12 alkyl- OH, N-(C _1-12 alkyl)amino, N,N-(C _1-12 alkyl) ₂ amino, N-(C _1-12 alkyl)carbamoyl, N,N-(C _1-12 alkyl) ₂ independently selected from carbamoyl, C _1-12 alkanoylamino, 3-10 membered saturated or unsaturated carbocyclyl, or 3-10 membered saturated or unsaturated heterocyclyl, said 3-10 membered saturated or unsaturated carbocyclyl; or a 3- to ₁₀ -membered saturated or unsaturated heterocyclyl optionally monosubstituted or independently polysubstituted with R6,
each R ₄ , R ₅ or R ₆ is halogen, hydroxyl, cyano, amino, carbamoyl, urea, carbamate, C _1-12 alkyl, C _1-12 haloalkyl, C _1-12 alkoxyl, C _1-12 haloalkoxyl, C _1-12 alkyl-OH, N-(C _1-12 alkyl)amino, N,N-(C _1-12 alkyl) ₂ amino, N-(C _1-12 alkyl)carbamoyl, N,N-(C independently selected from C _1-12 alkyl) ₂ carbamoyl, C _1-12 alkanoylamino;
m is 0, 1, 2, 3 or 4]
or a pharmaceutically acceptable salt thereof.

2. The compound of claim 1, wherein X is amino.

A compound according to claim 1, wherein W is C _1-12 alkylene or amino, optionally C _1-6 alkylene, optionally C _1-3 alkylene.

V is C _1-12 alkyl, C _1-12 alkoxyl, C _1-12 alkyl-OH, amino, carbamoyl, urea, carbamate, N-(C _1-12 alkyl)amino, N,N-(C _{1-12 12} alkyl) ₂ amino, C _1-12 alkanoylamino, N-(C _1-12 alkyl) carbamoyl, N,N-(C _1-12 alkyl) ₂ carbamoyl, 5- to 6-membered saturated or unsaturated carbocyclyl, or A compound according to claim 1, which is a 5-6 membered saturated or unsaturated heterocyclyl, which is optionally monosubstituted or independently polysubstituted with R ₃ .

The 5- to 6-membered saturated or unsaturated carbocyclyl or 5- to 6-membered saturated or unsaturated heterocyclyl is

5. The compound of claim 4, selected from

each R ₃ is halogen, cyano, amino, C _1-12 alkyl, C _1-12 alkoxyl, C _1-12 haloalkoxyl, N,N-(C _1-12 alkyl) ₂ amino, C _1-12 alkanoylamino , a 3- to 10-membered saturated or unsaturated carbocyclyl, or a 3- to 10-membered saturated or unsaturated heterocyclyl.

A is a 6- to 10-membered unsaturated monocyclic or polycyclic heterocyclyl having 1, 2, or 3 heteroatoms selected from N, O, or S, and one of the A rings or multiple —CH ₂ — groups optionally replaced by —C(O)— or —S(O) _a —, where a=0, 1 or 2. Compound.

wherein said 6-10 membered unsaturated heterocyclyl is selected from the group consisting of pyridinyl, pyridazinyl, pyridonyl, fused phenyl ring or fused pyridinyl ring, and one or more —CH ₂ — groups of 6-10 membered unsaturated heterocyclyl; is optionally replaced by -C(O)- or -S(O) _a -, where a=0, 1 or 2.

A is

8. The compound of claim 7, selected from

each R ₁ is halogen, cyano, amino, carbamoyl, urea, carbamate, C _1-12 alkyl, C _1-12 haloalkyl, C _1-12 alkoxyl, C _1-12 haloalkoxyl, C _1-12 alkyl-OH, N-(C _1-12 alkyl)amino, N,N-(C _1-12 alkyl) ₂ amino, N-(C _1-12 alkyl) carbamoyl, N,N-(C _1-12 alkyl) ₂ carbamoyl, or independently selected from 3- to 6-membered saturated carbocyclyl or heterocyclyl optionally wherein 3- to 6-membered saturated carbocyclyl or heterocyclyl is cyclopropyl, oxacyclopentanyl, oxetanyl, or 1,1-dioxothietanyl 2. The compound of claim 1, which is

Z is hydrogen, halogen, _C _1-12 alkyl, 3-12 membered saturated or unsaturated carbocyclyl, or 3-12 membered saturated or unsaturated heterocyclyl, which is optionally monosubstituted or independently and one or more —CH ₂ — groups in a 3- to 12-membered saturated or unsaturated carbocyclyl or 3- to 12-membered saturated or unsaturated heterocyclyl ring system are substituted with —C 2. A compound according to claim 1, optionally replaced by (O)- or -S(O) _a -, where a=0, 1 or 2.

3- to 12-membered saturated or unsaturated carbocyclyl, or 3- to 12-membered saturated or unsaturated heterocyclyl,

12. The compound of claim 11, selected from

2. The compound of claim 1, wherein each R ₃ is independently selected from halogen, cyano, C _1-12 alkyl, C _1-12 haloalkyl, C _1-12 alkoxyl, or C _1-12 haloalkoxyl.

2. The compound of claim 1, wherein W is methylene.

Formula (Ia):

[In the formula,
Ring A is a 6- to 10-membered unsaturated monocyclic or polycyclic heterocyclyl having 1, 2, or 3 heteroatoms selected from N, O, or S; one or more —CH ₂ — groups may optionally be replaced by —C(O)— or —S(O) _a —, a=0, 1 or 2;
The B ring is selected from 3-12 membered saturated or unsaturated carbocyclyl or 3-12 membered saturated or unsaturated heterocyclyl, wherein one or more —CH ₂ — groups in the B ring are —C(O )— or —S(O) _a —, where a=0, 1 or 2;
The Q ring is a 5- to 6-membered saturated or unsaturated carbocyclyl, or a 5- to 6-membered saturated or unsaturated heterocyclyl, and one or more —CH ₂ — groups in the Q ring are —C(O )— or —S(O) _a —, where a=0, 1 or 2;
W is a bond, O, S, imino, C _1-12 alkylene, C _1-12 alkylene-imino,
Each R ₁ is halogen, hydroxyl, cyano, amino, C _1-12 alkyl, C _1-12 haloalkyl, C _1-12 alkoxyl, C _1-12 haloalkoxyl, C _1-12 alkyl-OH, N—(C _1-12 alkyl)amino, N,N-(C _1-12 alkyl) ₂ amino, carbamoyl, N-(C _1-12 alkyl) carbamoyl, N,N-(C _1-12 alkyl) ₂ carbamoyl, 3- 10-membered saturated or unsaturated carbocyclyl or 3- to 10-membered saturated or unsaturated heterocyclyl, said 3- to 10-membered saturated or unsaturated carbocyclyl, or 3- to 10-membered saturated or unsaturated heterocyclyl is optionally monosubstituted or independently polysubstituted by R ₄ ;
Each R ₂ is halogen, hydroxyl, cyano, amino, C _1-12 alkyl, C _1-12 haloalkyl, C _1-12 alkoxyl, C _1-12 haloalkoxyl, C _1-12 alkyl-OH, N—(C _1-12 alkyl)amino, N,N-(C _1-12 alkyl) ₂ amino, carbamoyl, N-(C _1-12 alkyl) carbamoyl, N,N-(C _1-12 alkyl) ₂ carbamoyl selected by;
Each R ₃ is halogen, hydroxyl, cyano, amino, C _1-12 alkyl, C _1-12 haloalkyl, C _1-12 alkoxyl, C _1-12 haloalkoxyl, C _1-12 alkyl-OH, N—(C _1-12 alkyl)amino, N,N-(C _1-12 alkyl) ₂ amino, carbamoyl, N-(C _1-12 alkyl) carbamoyl, N,N-(C _1-12 alkyl) ₂ carbamoyl selected by;
Each R ₄ is halogen, hydroxyl, cyano, amino, carbamoyl, urea, carbamate, C _1-12 alkyl, C _1-12 haloalkyl, C _1-12 alkoxyl, C _1-12 haloalkoxyl, C _1-12 alkyl- OH, N-(C _1-12 alkyl)amino, N,N-(C _1-12 alkyl) ₂ amino, carbamoyl, N-(C _1-12 alkyl)carbamoyl, N,N-(C _1-12 alkyl ) independently selected from ₂ carbamoyl, C _1-12 alkanoylamino;
m is 0, 1, 2, 3 or 4;
n is 0, 1, 2, 3 or 4;
i is 0, 1, 2, 3 or 4]
or a pharmaceutically acceptable salt thereof.

A ring is

16. The compound of claim 15, selected from

B ring is

16. The compound of claim 15, selected from

Q ring is

16. The compound of claim 15, selected from

Each R ₁ is fluoro, chloro, cyano, amino, methyl, ethyl, methoxyl, fluoromethyl, difluoromethyl, trifluoromethyl, difluoromethoxy, methylamino, trifluoromethoxy, dimethylamino, isopropanylamino, ethoxyl, tri 16. The compound of claim 15 independently selected from fluoroethoxy, ethylamino, cyclopropyl, hydroxyethyl, oxacyclopentanyl, oxetanyl, or 1,1-dioxothietanyl.

each _R2 is fluoro, chloro, cyano, methyl, amino, ethyl, methoxyl, fluoromethyl, difluoromethyl, trifluoromethyl, difluoromethoxy, trifluoromethoxy, ethoxyl, methylamino, dimethylamino, ethylamino, isopropanyl 16. The compound of claim 15 independently selected from amino, hydromethyl, hydroxyethyl.

_each R3 independently from fluoro, chloro, cyano, methyl, ethyl, methoxyl, fluoromethyl, difluoromethyl, trifluoromethyl, difluoromethoxyl, methylamino, dimethylamino, isopropylamino, ethoxyl, trifluoroethoxy, ethylamino; 16. A compound according to claim 15, which is selected from

16. The compound of claim 15, wherein the A ring is pyridonyl, the B ring is phenyl and the Q ring is pyridinyl.

16. The compound of claim 15, wherein W is methylene.

Formula (Ib):

[In the formula,
R ₁ is hydroxyl, cyano, amino, C _1-12 alkyl, C _1-12 haloalkyl, C _1-12 alkoxyl, C _1-12 haloalkoxyl, C _1-12 alkyl-OH, N—(C _1-12 alkyl)amino, N,N-(C _1-12 alkyl) ₂ amino, N-(C _1-12 alkyl) carbamoyl, N,N-(C _1-12 alkyl) ₂ carbamoyl, 3-10 membered saturated or unsaturated carbocyclyl, or 3- to 10-membered saturated or unsaturated heterocyclyl, which is optionally monosubstituted or independently polysubstituted by _R4 ;
Each R ₂ is halogen, hydroxyl, cyano, amino, carbamoyl, urea, carbamate, C _1-12 alkyl, C _1-12 haloalkyl, C _1-12 alkoxyl, C _1-12 haloalkoxyl, C _1-12 alkyl- OH, N-(C _1-12 alkyl)amino, N,N-(C _1-12 alkyl) ₂ amino, N-(C _1-12 alkyl)carbamoyl, N,N-(C _1-12 alkyl) ₂ independently selected from carbamoyl;
Each R ₃ is halogen, hydroxyl, cyano, amino, carbamoyl, urea, carbamate, C _1-12 alkyl, C _1-12 haloalkyl, C _1-12 alkoxyl, C _1-12 haloalkoxyl, C _1-12 alkyl- OH, N-(C _1-12 alkyl)amino, N,N-(C _1-12 alkyl) ₂ amino, N-(C _1-12 alkyl)carbamoyl, N,N-(C _1-12 alkyl) ₂ independently selected from carbamoyl;
Each R ₄ is halogen, hydroxyl, cyano, amino, carbamoyl, urea, carbamate, C _1-12 alkyl, C _1-12 haloalkyl, C _1-12 alkoxyl, C _1-12 haloalkoxyl, C _1-12 alkyl- OH, N-(C _1-12 alkyl)amino, N,N-(C _1-12 alkyl) ₂ amino, carbamoyl, N-(C _1-12 alkyl)carbamoyl, N,N-(C _1-12 alkyl ) independently selected from ₂ carbamoyl, C _1-12 alkanoylamino;
W is a bond, O, S, imino, C _1-12 alkylene, C _1-12 alkylene-imino,
n is 0, 1, 2, 3 or 4;
i is 0, 1, 2, 3 or 4]
or a pharmaceutically acceptable salt thereof.

25. The compound of claim 24, wherein R ₁ is C _1-12 alkyl.

25. The compound of claim 24, wherein _R2 is halogen and n=1.

25. A compound according to claim 24 _, wherein R3 is halogen and i=1.

25. The compound of claim 24, wherein W is methylene.

8-(2,6-dimethylpyridin-4-yl)-7-(4-fluorophenyl)-2-[(3-fluoropyridin-2-yl)methyl]-[1,2,4]triazolo[1 ,5-c]pyrimidin-5-amine,
7-(4-fluorophenyl)-2-((3-fluoropyridin-2-yl)methyl)-8-(2-methylpyridin-4-yl)-[1,2,4]triazolo[1,5 -c]pyrimidin-5-amine,
8-(2-chloropyridin-4-yl)-7-(4-fluorophenyl)-2-((3-fluoropyridin-2-yl)methyl)-[1,2,4]triazolo[1,5 -c]pyrimidin-5-amine,
2-[(2,6-difluorophenyl)methyl]-7-(4-fluorophenyl)-8-[2-(trifluoromethyl)pyridin-4-yl]-[1,2,4]triazolo[1 ,5-c]pyrimidin-5-amine,
2-(2,6-difluorobenzyl)-7-(4-fluorophenyl)-8-(2-methoxypyridin-4-yl)-[1,2,4]triazolo[1,5-c]pyrimidine- 5-amine,
2-(2,6-difluorobenzyl)-7-(4-fluorophenyl)-8-(pyridazin-4-yl)-[1,2,4]triazolo[1,5-c]pyrimidin-5-amine ,
7-(4-fluorophenyl)-8-(2-methylpyridin-4-yl)-2-[(1,3-thiazol-4-yl)methyl]-[1,2,4]triazolo[1, 5-c]pyrimidin-5-amine,
2-[(3-chlorophenyl)methyl]-7-(4-fluorophenyl)-8-(2-methylpyridin-4-yl)-[1,2,4]triazolo[1,5-c]pyrimidine- 5-amine,
5-(5-amino-2-(2,6-difluorobenzyl)-7-(4-fluorophenyl)-[1,2,4]triazolo[1,5-c]pyrimidin-8-yl)-1 -methylpyridin-2(1H)-one,
2-(2,6-difluorobenzyl)-8-(2-(dimethylamino)pyridin-4-yl)-7-(4-fluorophenyl)-[1,2,4]triazolo[1,5-c ] pyrimidine-5-amine,
7-(4-fluorophenyl)-8-(2-methylpyridin-4-yl)-2-[(1,3-thiazol-4-yl)methyl]-[1,2,4]triazolo[1, 5-c]pyrimidin-5-amine,
2-[1-(2,6-difluorophenyl)ethyl]-7-(4-fluorophenyl)-8-(2-methylpyridin-4-yl)-[1,2,4]triazolo[1,5 -c]pyrimidin-5-amine,
2-[(2,6-difluorophenyl)methyl]-8-(2,5-dimethylpyridin-4-yl)-7-(4-fluorophenyl)-[1,2,4]triazolo[1,5 -c]pyrimidin-5-amine,
8-(2,6-dimethylpyridin-4-yl)-7-(4-fluorophenyl)-2-((3-fluoropyridin-2-yl)methyl)-[1,2,4]triazolo[1 ,5-c]pyrimidin-5-amine,
2-[(6-chloropyridin-2-yl)methyl]-7-(4-fluorophenyl)-8-(2-methylpyridin-4-yl)-[1,2,4]triazolo[1,5 -c]pyrimidin-5-amine,
2-(2,6-difluorobenzyl)-8-(2,3-dimethylpyridin-4-yl)-7-(4-fluorophenyl)-[1,2,4]triazolo[1,5-c] pyrimidine-5-amine,
2-((6-(dimethylamino)pyridin-2-yl)methyl)-7-(4-fluorophenyl)-8-(2-methylpyridin-4-yl)-[1,2,4]triazolo [ 1,5-f]pyrimidin-5-amine,
8-(2-chloro-6-methylpyridin-4-yl)-7-(4-fluorophenyl)-2-((3-fluoropyridin-2-yl)methyl)-[1,2,4]triazolo [1,5-c]pyrimidin-5-amine,
6-((5-amino-7-(4-fluorophenyl)-8-(2-methylpyridin-4-yl)-[1,2,4]triazolo[1,5-f]pyrimidin-2-yl ) methyl) picolinonitrile,
5-(5-amino-2-[[3-(difluoromethoxy)pyridin-2-yl]methyl]-7-(4-fluorophenyl)-[1,2,4]triazolo[1,5-c] pyrimidin-8-yl)-1-methyl-1,2-dihydropyridin-2-one,
5-(5-amino-2-((3-fluoropyridin-2-yl)methyl)-7-(oxazol-2-yl)-[1,2,4]triazolo[1,5-c]pyrimidine- 8-yl)-1-methylpyridin-2(1H)-one,
5-(5-amino-2-(2,6-difluorobenzyl)-7-(oxazol-2-yl)-[1,2,4]triazolo[1,5-c]pyrimidin-8-yl)- 1-methylpyridin-2(1H)-one,
5-[5-amino-7-(4-fluorophenyl)-2-[(3-fluoropyridin-2-yl)methyl]-[1,2,4]triazolo[1,5-c]pyrimidine-8 -yl]-1-[(3S)-oxolan-3-yl]-1,2-dihydropyridin-2-one,
5-[5-amino-2-[(2,6-difluorophenyl)methyl]-7-(6-methylpyridin-3-yl)-[1,2,4]triazolo[1,5-c]pyrimidine -8-yl]-1-methyl-1,2-dihydropyridin-2-one,
5-[5-amino-2-[(2,6-difluorophenyl)methyl]-7-(2H-1,2,3-triazol-2-yl)-[1,2,4]triazolo[1, 5-c]pyrimidin-8-yl]-1-methyl-1,2-dihydropyridin-2-one,
5-(5-amino-2-(2,6-difluorobenzyl)-7-(5-methyloxazol-2-yl)-[1,2,4]triazolo[1,5-c]pyrimidine-8- yl)-1-methylpyridin-2(1H)-one,
5-(5-amino-2-(2,6-difluorobenzyl)-7-(4-methyloxazol-2-yl)-[1,2,4]triazolo[1,5-c]pyrimidine-8- yl)-1-methylpyridin-2(1H)-one,
5-(5-amino-7-chloro-2-(2,6-difluorobenzyl)-[1,2,4]triazolo[1,5-c]pyrimidin-8-yl)-1-methylpyridine-2 (1H)-on,
5-(5-amino-7-(4-fluorophenyl)-2-((3-fluoropyridin-2-yl)methyl)-[1,2,4]triazolo[1,5-c]pyrimidine-8 -yl)-1,3-dimethylpyridin-2(1H)-one,
6-(5-amino-7-(4-fluorophenyl)-2-((3-fluoropyridin-2-yl)methyl)-[1,2,4]triazolo[1,5-f]pyrimidine-8 -yl)-2-methylpyridazin-3(2H)-one,
2-((3-fluoropyridin-2-yl)methyl)-8-(imidazo[1,2-a]pyridin-6-yl)-7-(oxazol-2-yl)-[1,2,4 ]triazolo[1,5-c]pyrimidin-5-amine,
7-(4-fluorophenyl)-2-((3-fluoropyridin-2-yl)methyl)-8-(imidazo[1,2-a]pyridin-6-yl)-[1,2,4] triazolo[1,5-c]pyrimidin-5-amine,
2-[(2,6-difluorophenyl)methyl]-8-(2,6-dimethylpyridin-4-yl)-7-(1,3-oxazol-2-yl)-[1,2,4] triazolo[1,5-c]pyrimidin-5-amine,
5-(5-amino-7-(4-fluorophenyl)-2-((3-fluoropyridin-2-yl)methyl)-[1,2,4]triazolo[1,5-c]pyrimidine-8 -yl)-1-ethylpyridin-2(1H)-one,
5-(5-amino-2-((6-aminopyridin-2-yl)methyl)-7-(4-fluorophenyl)-[1,2,4]triazolo[1,5-c]pyrimidine-8 -yl)-1-methylpyridin-2(1H)-one,
5-(5-amino-2-(2,6-difluorobenzyl)-7-(oxazol-2-yl)-[1,2,4]triazolo[1,5-c]pyrimidin-8-yl)- 1-methylpyridin-2(1H)-one,
6-[[5-amino-7-(4-fluorophenyl)-8-[imidazo[1,2-a]pyridin-6-yl]-[1,2,4]triazolo[1,5-c] pyrimidin-2-yl]methyl]pyridin-2-amine,
8-(2-aminopyridin-4-yl)-7-(4-fluorophenyl)-2-((3-fluoropyridin-2-yl)methyl)-[1,2,4]triazolo[1,5 -c]pyrimidin-5-amine,
5-[5-amino-7-(3,4-difluorophenyl)-2-[(3-fluoropyridin-2-yl)methyl]-[1,2,4]triazolo[1,5-c]pyrimidine -8-yl]-1-methyl-1,2-dihydropyridin-2-one,
5-(5-amino-7-(3-fluorophenyl)-2-((3-fluoropyridin-2-yl)methyl)-[1,2,4]triazolo[1,5-c]pyrimidine-8 -yl)-1-methylpyridin-2(1H)-one,
5-(5-amino-7-(4-(difluoromethyl)phenyl)-2-((3-fluoropyridin-2-yl)methyl)-[1,2,4]triazolo[1,5-c] pyrimidin-8-yl)-1-methylpyridin-2(1H)-one,
5-[5-amino-7-(4-fluorophenyl)-2-[(1,3-thiazol-2-yl)methyl]-[1,2,4]triazolo[1,5-c]pyrimidine- 8-yl]-1-methyl-1,2-dihydropyridin-2-one,
7-(4-fluorophenyl)-2-((3-fluoropyridin-2-yl)methyl)-8-(2-(methylamino)pyridin-4-yl)-[1,2,4]triazolo [ 1,5-c]pyrimidin-5-amine,
5-(5-amino-2-(2,6-difluorobenzyl)-7-(thiazol-2-yl)-[1,2,4]triazolo[1,5-c]pyrimidin-8-yl)- 1-methylpyridin-2(1H)-one,
7-(4-fluorophenyl)-2-((6-methylpyridin-2-yl)methyl)-8-(2-methylpyridin-4-yl)-[1,2,4]triazolo[1,5 -c]pyrimidin-5-amine,
7-(4-fluorophenyl)-8-(2-methylpyridin-4-yl)-N2-(pyridin-2-yl)-[1,2,4]triazolo[1,5-c]pyrimidine-2 , 5-diamine,
7-(4-fluorophenyl)-2-((6-methylpyridin-2-yl)methyl)-8-(2,6-dimethylpyridin-4-yl)-[1,2,4]triazolo[1 ,5-c]pyrimidin-5-amine,
2-(2,6-difluorobenzyl)-8-(2,6-dimethylpyridin-4-yl)-7-(4-fluorophenyl)-[1,2,4]triazolo[1,5-c] pyrimidine-5-amine,
3-amino-N-(2-(difluoromethoxy)benzyl)-5-(4-fluorophenyl)-6-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)pyrazine-2- carboxamide,
8-(2,6-dimethylpyridin-4-yl)-7-(4-fluorophenyl)-2-((3-methoxypyridin-2-yl)methyl)-[1,2,4]triazolo[1 ,5-c]pyrimidin-5-amine,
8-(2-amino-6-methylpyridin-4-yl)-2-(2,6-difluorobenzyl)-7-(4-fluorophenyl)-[1,2,4]triazolo[1,5- c] pyrimidin-5-amine,
5-[5-amino-7-(4-fluorophenyl)-2-[(3-fluoropyridin-2-yl)methyl]-[1,2,4]triazolo[1,5-c]pyrimidine-8 -yl]-1-(propan-2-yl)-1,2-dihydropyridin-2-one,
5-(5-amino-7-(4-chlorophenyl)-2-((3-fluoropyridin-2-yl)methyl)-[1,2,4]triazolo[1,5-c]pyrimidine-8- yl)-1-methylpyridin-2(1H)-one,
4-(5-amino-2-((3-fluoropyridin-2-yl)methyl)-8-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-[1,2, 4] triazolo[1,5-c]pyrimidin-7-yl)benzonitrile,
5-[5-amino-7-(4-fluorophenyl)-2-[(1,3-thiazol-4-yl)methyl]-[1,2,4]triazolo[1,5-c]pyrimidine- 8-yl]-1-methyl-1,2-dihydropyridin-2-one,
5-(5-amino-2-((3-fluoropyridin-2-yl)methyl)-7-(1-methyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[1, 5-c]pyrimidin-8-yl)-1-methylpyridin-2(1H)-one,
5-(5-amino-2-(2,6-difluorobenzyl)-7-(4-fluorophenyl)-[1,2,4]triazolo[1,5-c]pyrimidin-8-yl)-1 -(1,1-dioxidothiethan-3-yl)pyridin-2(1H)-one,
5-(5-amino-2-((3-fluoropyridin-2-yl)methyl)-7-(4-methoxyphenyl)-[1,2,4]triazolo[1,5-c]pyrimidine-8 -yl)-1-methylpyridin-2(1H)-one,
5-(5-amino-2-((3-fluoropyridin-2-yl)methyl)-7-(4-(trifluoromethyl)phenyl)-[1,2,4]triazolo[1,5-c ] pyrimidin-8-yl)-1-methylpyridin-2(1H)-one,
5-[5-amino-2-[(3-fluoropyridin-2-yl)methyl]-7-(1H-pyrazol-1-yl)-[1,2,4]triazolo[1,5-c] pyrimidin-8-yl]-1-methyl-1,2-dihydropyridin-2-one,
5-(5-amino-7-(2,4-difluorophenyl)-2-((3-fluoropyridin-2-yl)methyl)-[1,2,4]triazolo[1,5-c]pyrimidine -8-yl)-1-methylpyridin-2(1H)-one,
7-(4-fluorophenyl)-2-((3-fluoropyridin-2-yl)methyl)-8-(1-methyl-1H-benzo[d]imidazol-6-yl)-[1,2, 4] triazolo[1,5-c]pyrimidin-5-amine,
7-(4-fluorophenyl)-2-((3-fluoropyridin-2-yl)methyl)-8-(1-methyl-1H-benzo[d]imidazol-6-yl)-[1,2, 4] triazolo[1,5-c]pyrimidin-5-amine,
5-(5-amino-2-(2,6-difluorobenzyl)-7-(oxazol-2-yl)-[1,2,4]triazolo[1,5-c]pyrimidin-8-yl)- 1-methylpyridin-2(1H)-one,
7-(4-fluorophenyl)-8-[imidazo[1,2-a]pyridin-6-yl]-2-[(2-methyl-1,3-thiazol-4-yl)methyl]-[1 ,2,4]triazolo[1,5-c]pyrimidin-5-amine,
7-(4-fluorophenyl)-2-((3-fluoropyridin-2-yl)methyl)-8-(1-methyl-1H-benzo[d]imidazol-6-yl)-[1,2, 4] triazolo[1,5-c]pyrimidin-5-amine,
5-(5-amino-7-(3-chlorophenyl)-2-((3-fluoropyridin-2-yl)methyl)-[1,2,4]triazolo[1,5-c]pyrimidine-8- yl)-1-methylpyridin-2(1H)-one,
5-(5-amino-2-[[3-(difluoromethoxy)pyridin-2-yl]methyl]-7-(1,3-oxazol-2-yl)-[1,2,4]triazolo[1 ,5-c]pyrimidin-8-yl)-1-methyl-1,2-dihydropyridin-2-one,
5-(5-amino-2-(2,6-difluorobenzyl)-7-(oxazol-2-yl)-[1,2,4]triazolo[1,5-c]pyrimidin-8-yl)- 1-methylpyridin-2(1H)-one,
2-((3-(difluoromethoxy)pyridin-2-yl)methyl)-7-(4-fluorophenyl)-8-(imidazo[1,2-a]pyridin-6-yl)-[1,2 ,4]triazolo[1,5-c]pyrimidin-5-amine,
2-((3-(difluoromethoxy)pyridin-2-yl)methyl)-8-(imidazo[1,2-a]pyridin-6-yl)-7-(oxazol-2-yl)-[1, 2,4]triazolo[1,5-c]pyrimidin-5-amine,
8-(1H-benzo[d]imidazol-6-yl)-7-(4-fluorophenyl)-2-((3-fluoropyridin-2-yl)methyl)-[1,2,4]triazolo [ 1,5-c]pyrimidin-5-amine,
5-(5-amino-7-(3,5-difluorophenyl)-2-((3-fluoropyridin-2-yl)methyl)-[1,2,4]triazolo[1,5-c]pyrimidine -8-yl)-1-methylpyridin-2(1H)-one,
5-(5-amino-2-((3-fluoropyridin-2-yl)methyl)-7-(3-methoxyphenyl)-[1,2,4]triazolo[1,5-c]pyrimidine-8 -yl)-1-methylpyridin-2(1H)-one,
5-(5-amino-7-(2-chlorophenyl)-2-((3-fluoropyridin-2-yl)methyl)-[1,2,4]triazolo[1,5-c]pyrimidine-8- yl)-1-methylpyridin-2(1H)-one,
5-(5-amino-2-(2,6-difluorobenzyl)-7-(oxazol-2-yl)-[1,2,4]triazolo[1,5-c]pyrimidin-8-yl)- 1-isopropylpyridin-2(1H)-one,
5-(5-amino-2-((3-fluoropyridin-2-yl)methyl)-7-(oxazol-2-yl)-[1,2,4]triazolo[1,5-c]pyrimidine- 8-yl)-1-isopropylpyridin-2(1H)-one,
8-(2-amino-6-methylpyridin-4-yl)-2-(2,6-difluorobenzyl)-7-(oxazol-2-yl)-[1,2,4]triazolo[1,5 -c]pyrimidin-5-amine,
8-(2-chloro-6-methylpyridin-4-yl)-2-((3-fluoropyridin-2-yl)methyl)-7-(oxazol-2-yl)-[1,2,4] triazolo[1,5-c]pyrimidin-5-amine,
4-(5-amino-2-(2,6-difluorobenzyl)-7-(oxazol-2-yl)-[1,2,4]triazolo[1,5-c]pyrimidin-8-yl)- 6-methylpicolinonitrile,
8-(2-cyclopropyl-6-methylpyridin-4-yl)-2-(2,6-difluorobenzyl)-7-(oxazol-2-yl)-[1,2,4]triazolo[1, 5-c]pyrimidin-5-amine,
2-(2,6-difluorobenzyl)-8-(2-(difluoromethoxy)pyridin-4-yl)-7-(oxazol-2-yl)-[1,2,4]triazolo[1,5- c] pyrimidin-5-amine,
8-(2-(difluoromethoxy)pyridin-4-yl)-2-((3-fluoropyridin-2-yl)methyl)-7-(oxazol-2-yl)-[1,2,4]triazolo [1,5-c]pyrimidin-5-amine,
8-(2-(difluoromethoxy)-6-methylpyridin-4-yl)-2-((3-fluoropyridin-2-yl)methyl)-7-(oxazol-2-yl)-[1,2 ,4]triazolo[1,5-c]pyrimidin-5-amine,
8-(benzo[d]thiazol-6-yl)-7-(4-fluorophenyl)-2-((3-fluoropyridin-2-yl)methyl)-[1,2,4]triazolo[1, 5-c]pyrimidin-5-amine,
7-(4-fluorophenyl)-2-((3-fluoropyridin-2-yl)methyl)-8-(quinolin-6-yl)-[1,2,4]triazolo[1,5-c] pyrimidine-5-amine,
2-((3-fluoropyridin-2-yl)methyl)-8-(1-methyl-1H-benzo[d]imidazol-6-yl)-7-(oxazol-2-yl)-[1,2 ,4]triazolo[1,5-c]pyrimidin-5-amine,
2-(2,6-difluorobenzyl)-8-(1-methyl-1H-benzo[d]imidazol-6-yl)-7-(oxazol-2-yl)-[1,2,4]triazolo [ 1,5-c]pyrimidin-5-amine,
5-[5-amino-2-[(2,6-difluorophenyl)methyl]-7-(pyridin-2-yl)-[1,2,4]triazolo[1,5-c]pyrimidine-8- yl]-1-methyl-1,2-dihydropyridin-2-one,
2-((3-fluoropyridin-2-yl)methyl)-8-(imidazo[1,2-a]pyridin-6-yl)-7-(1H-1,2,3-triazol-1-yl )-[1,2,4]triazolo[1,5-c]pyrimidin-5-amine,
2-[(3-fluoropyridin-2-yl)methyl]-8-[imidazo[1,2-a]pyridin-6-yl]-7-(2H-1,2,3-triazol-2-yl )-[1,2,4]triazolo[1,5-c]pyrimidin-5-amine,
5-(5-amino-7-(4-fluorophenyl)-2-((3-fluoropyridin-2-yl)methyl)-[1,2,4]triazolo[1,5-c]pyrimidine-8 -yl)-1-(2-hydroxyethyl)pyridin-2(1H)-one 7-(4-fluorophenyl)-2-((3-fluoropyridin-2-yl)methyl)-8-(quinoxaline- 6-yl)-[1,2,4]triazolo[1,5-c]pyrimidin-5-amine,
5-(5-amino-2-((3-fluoropyridin-2-yl)methyl)-7-(1-methyl-1H-indol-5-yl)-[1,2,4]triazolo[1, 5-c]pyrimidin-8-yl)-1-methylpyridin-2(1H)-one,
5-(5-amino-2-((3-fluoropyridin-2-yl)methyl)-7-(2-methoxyphenyl)-[1,2,4]triazolo[1,5-c]pyrimidine-8 -yl)-1-methylpyridin-2(1H)-one,
2-((3-fluoropyridin-2-yl)methyl)-8-(3-methylimidazo[1,2-a]pyridin-6-yl)-7-(oxazol-2-yl)-[1, 2,4]triazolo[1,5-c]pyrimidin-5-amine,
2-((3-fluoropyridin-2-yl)methyl)-N7,N7-dimethyl-8-(3-methylimidazo[1,2-a]pyridin-6-yl)-[1,2,4] triazolo[1,5-c]pyrimidine-5,7-diamine,
2-((3-fluoropyridin-2-yl)methyl)-8-(3-methylimidazo[1,2-a]pyridin-6-yl)-7-(pyrrolidin-1-yl)-[1, 2,4]triazolo[1,5-c]pyrimidin-5-amine,
2-((3-fluoropyridin-2-yl)methyl)-8-(3-methylimidazo[1,2-a]pyridin-6-yl)-7-morpholino-[1,2,4]triazolo [ 1,5-c]pyrimidin-5-amine,
(S)-7-(4-fluorophenyl)-8-(1-methyl-1H-benzo[d]imidazol-6-yl)-2-((1-methylpyrrolidin-2-yl)methyl)-[ 1,2,4]triazolo[1,5-c]pyrimidin-5-amine,
(R)-7-(4-fluorophenyl)-8-(1-methyl-1H-benzo[d]imidazol-6-yl)-2-((1-methylpyrrolidin-2-yl)methyl)-[ 1,2,4]triazolo[1,5-c]pyrimidin-5-amine,
7-(4-fluorophenyl)-8-(3-methylimidazo[1,2-a]pyridin-6-yl)-2-((tetrahydrofuran-3-yl)methyl)-[1,2,4] triazolo[1,5-c]pyrimidin-5-amine (isomer 1),
7-(4-fluorophenyl)-8-(3-methylimidazo[1,2-a]pyridin-6-yl)-2-((tetrahydrofuran-3-yl)methyl)-[1,2,4] triazolo[1,5-c]pyrimidin-5-amine (isomer 2),
8-(3-methylimidazo[1,2-a]pyridin-6-yl)-7-(oxazol-2-yl)-2-((tetrahydrofuran-2-yl)methyl)-[1,2,4 ]triazolo[1,5-c]pyrimidin-5-amine (isomer 1),
8-(3-methylimidazo[1,2-a]pyridin-6-yl)-7-(oxazol-2-yl)-2-((tetrahydrofuran-2-yl)methyl)-[1,2,4 ]triazolo[1,5-c]pyrimidin-5-amine (isomer 2),
8-(3-methylimidazo[1,2-a]pyridin-6-yl)-7-(oxazol-2-yl)-2-((tetrahydrofuran-3-yl)methyl)-[1,2,4 ]triazolo[1,5-c]pyrimidin-5-amine (isomer 1),
8-(3-methylimidazo[1,2-a]pyridin-6-yl)-7-(oxazol-2-yl)-2-((tetrahydrofuran-3-yl)methyl)-[1,2,4 ]triazolo[1,5-c]pyrimidin-5-amine (isomer 2),
2-(2,6-difluorobenzyl)-8-(3-methylimidazo[1,2-a]pyridin-6-yl)-7-(4-methylpiperazin-1-yl)-[1,2, 4] triazolo[1,5-c]pyrimidin-5-amine,
2-(2,6-difluorobenzyl)-7-(3-methoxyazetidin-1-yl)-8-(3-methylimidazo[1,2-a]pyridin-6-yl)-[1,2 ,4]triazolo[1,5-c]pyrimidin-5-amine,
2-((3-fluoropyridin-2-yl)methyl)-8-(3-methylimidazo[1,2-a]pyridin-6-yl)-7-(2-oxa-6-azaspiro[3. 4]octan-6-yl)-[1,2,4]triazolo[1,5-c]pyrimidin-5-amine,
2-((3-fluoropyridin-2-yl)methyl)-8-(3-methylimidazo[1,2-a]pyridin-6-yl)-7-(2-methylmorpholino)-[1,2 ,4]triazolo[1,5-c]pyrimidin-5-amine (isomer 1),
2-((3-fluoropyridin-2-yl)methyl)-8-(3-methylimidazo[1,2-a]pyridin-6-yl)-7-(2-methylmorpholino)-[1,2 , 4]triazolo[1,5-c]pyrimidin-5-amine (isomer 2), 2-((3-fluoropyridin-2-yl)methyl)-8-(3-methylimidazo[1,2- a]pyridin-6-yl)-7-(3-methylmorpholino)-[1,2,4]triazolo[1,5-c]pyrimidin-5-amine (isomer 1),
2-((3-fluoropyridin-2-yl)methyl)-8-(3-methylimidazo[1,2-a]pyridin-6-yl)-7-(3-methylmorpholino)-[1,2 ,4]triazolo[1,5-c]pyrimidin-5-amine (isomer 2),
7-(4-fluorophenyl)-2-(2-methoxyethyl)-8-(3-methylimidazo[1,2-a]pyridin-6-yl)-[1,2,4]triazolo[1, 5-c]pyrimidin-5-amine,
7-(4-fluorophenyl)-8-(1-methyl-1H-benzo[d]imidazol-6-yl)-2-((1-methylpyrrolidin-2-yl)methyl)-[1,2, 4] triazolo[1,5-c]pyrimidin-5-amine,
7-(3-fluoro-1H-pyrazol-1-yl)-2-((3-fluoropyridin-2-yl)methyl)-8-(3-methylimidazo[1,2-a]pyridine-6- yl)-[1,2,4]triazolo[1,5-c]pyrimidin-5-amine,
7-(4-fluoro-1H-pyrazol-1-yl)-2-((3-fluoropyridin-2-yl)methyl)-8-(3-methylimidazo[1,2-a]pyridine-6- yl)-[1,2,4]triazolo[1,5-c]pyrimidin-5-amine,
2-((3-fluoropyridin-2-yl)methyl)-8-(3-methylimidazo[1,2-a]pyridin-6-yl)-7-(2-oxa-6-azaspiro[3. 3]heptan-6-yl)-[1,2,4]triazolo[1,5-c]pyrimidin-5-amine,
7-(azetidin-1-yl)-2-((3-fluoropyridin-2-yl)methyl)-8-(3-methylimidazo[1,2-a]pyridin-6-yl)-[1, 2,4]triazolo[1,5-c]pyrimidin-5-amine,
2-(2-(dimethylamino)ethyl)-7-(4-fluorophenyl)-8-(3-methylimidazo[1,2-a]pyridin-6-yl)-[1,2,4]triazolo [1,5-c]pyrimidin-5-amine,
2-(2,6-difluorobenzyl)-8-(3-methylimidazo[1,2-a]pyridin-6-yl)-7-morpholino-[1,2,4]triazolo[1,5-c ] pyrimidine-5-amine,
(S)-7-(4-fluorophenyl)-8-(3-methylimidazo[1,2-a]pyridin-6-yl)-2-((1-methylpyrrolidin-2-yl)methyl)- [1,2,4]triazolo[1,5-c]pyrimidin-5-amine,
2-(2,6-difluorobenzyl)-8-(3-methylimidazo[1,2-a]pyridin-6-yl)-7-(pyrrolidin-1-yl)-[1,2,4]triazolo [1,5-c]pyrimidin-5-amine,
7-(azetidin-1-yl)-2-(2,6-difluorobenzyl)-8-(3-methylimidazo[1,2-a]pyridin-6-yl)-[1,2,4]triazolo [1,5-c]pyrimidin-5-amine,
(R)-7-(4-fluorophenyl)-8-(3-methylimidazo[1,2-a]pyridin-6-yl)-2-((1-methylpyrrolidin-2-yl)methyl)- [1,2,4]triazolo[1,5-c]pyrimidin-5-amine,
2-(2-methoxyethyl)-8-(3-methylimidazo[1,2-a]pyridin-6-yl)-7-(oxazol-2-yl)-[1,2,4]triazolo[1 ,5-c]pyrimidin-5-amines.

30. A pharmaceutical composition comprising one or more compounds according to any one of claims 1-29 and a pharmaceutically acceptable carrier.

30. Use of one or more compounds according to any one of claims 1-29 in the manufacture of a medicament for treating an adenosine receptor-related disease.

Adenosine receptor-related diseases include cancer, Parkinson's disease, epilepsy, cerebral ischemia and stroke, depression, cognitive impairment, HIV, adenosine deaminase-severe combined immunodeficiency (ADA-SCID), acute and chronic heart failure, chronic 32. Use according to claim 31, which is obstructive pulmonary disease (COPD), or asthma.

33. Use according to claim 32, wherein the cancer is NSCLC, RCC, prostate cancer or breast cancer.

32. Use according to claim 31, wherein the medicament is used in combination with radiotherapy, chemotherapy or immunotherapy.

30. A pharmaceutical composition for treating an adenosine receptor-related disease, comprising an effective amount of one or more compounds according to any one of claims 1-29 .

Adenosine receptor-related diseases include cancer, Parkinson's disease, epilepsy, cerebral ischemia and stroke, depression, cognitive impairment, HIV, adenosine deaminase-severe combined immunodeficiency (ADA-SCID), acute and chronic heart failure, chronic 36. The pharmaceutical composition of claim 35, which is obstructive pulmonary disease (COPD), or asthma .

37. The pharmaceutical composition of Claim 36, wherein the cancer is NSCLC, RCC, prostate cancer, or breast cancer .

38. The pharmaceutical composition of any one of claims 35-37, further comprising one or more immunotherapeutic or chemotherapeutic agents .

39. The pharmaceutical composition according to any one of claims 35-38, for use in combination therapy with radiotherapy .

38. The pharmaceutical composition according to any one of claims 35-37, for use in combination with an immunotherapeutic agent or a chemotherapeutic agent .

said immunotherapeutic agent is selected from the group consisting of anti-PD-1/PD-L1 antibodies, anti-CTLA-4 antibodies, anti-CD73 antibodies, anti-CD39 antibodies, anti-CCR2 antibodies and any combination thereof 41. The pharmaceutical composition of claim 40 , wherein

42. Claim 40 or 41, wherein said chemotherapeutic agent is selected from the group consisting of platinum-based chemotherapeutic agents (cisplatin, oxaliplatin), docetaxel, paclitaxel, doxorubicin, etoposide, mitoxantrone and any combination thereof. pharmaceutical composition of