Aminoheteroaryl compounds and preparation method and use thereof

1. A compound represented by the following general formula (I) or a pharmaceutically acceptable salt thereof,

wherein:

R 1 is selected from H, C 1 -C 6 alkyl, C 1 -C 6 alkyl substituted by 1-3 halogen, C 3 -C 8 cycloalkyl, C 3 -C 8 cycloalkyl substituted by 1-3 halogen, —CONR′R″, aryl, heteroaryl or nitrogen-containing saturated heterocyclyl;

R 2 is selected from —OR 3 , —SR 3 or —NR 3 , wherein R 3 is H, C 1 -C 6 alkyl, C 1 -C 6 alkyl substituted by 1-3 halogen, —(CR′R″) 0-6 -aryl, —(CR′R″) 0-6 -heteroaryl or —(CR′R″) 0-6 — nitrogen-containing saturated heterocyclyl; and

wherein:

said aryl, heteroaryl and nitrogen-containing saturated heterocyclyl is unsubstituted or substituted by halogen, C 1 -C 6 alkyl, C 1 -C 6 alkyl substituted by aryl, C 1 -C 6 alkoxy, C 3 -C 8 cycloalkyl, —NR′R″, —COR′″, —COOR′″, —SOOR′″ or —OH;

said R′ and R″ are each independently H, C 1 -C 4 alkyl or C 1 -C 4 alkyl substituted by 1-3 halogen; and

said R′″ is selected from the following groups: H, C 1 -C 4 alkyl, C 1 -C 4 alkyl substituted by 1-3 halogen, aryl that is unsubstituted or substituted by halogen, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, —CN, —NH 2 or —OH and heteroaryl that is unsubstituted or substituted by—halogen, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, —CN, —NH 2 or —OH.

2. A compound according to claim 1 or a pharmaceutically acceptable salt thereof, having the structure of the following formula (II):

wherein R 1 and R 3 are as defined in claim 1 .

3. The compound of formula (II) according to claim 2 or a pharmaceutically acceptable salt thereof, wherein R 3 is —(CR′R″) 0-4 -aryl or —(CR′R″) 0-4 -heteroaryl, said aryl or heteroaryl is unsubstituted or substituted by halogen, C 1 -C 4 alkyl or C 1 -C 4 alkoxy, said R′ and R″ are each independently H, C 1 -C 4 alkyl or C 1 -C 4 alkyl substituted by 1-3 halogen.

4. The compound of formula (II) according to claim 3 or a pharmaceutically acceptable salt thereof, wherein R 3 is —(CR′R″) 1-2 -aryl, said aryl is unsubstituted or substituted by halogen or C 1 -C 4 alkyl, said R′ and R″ are each independently H or —C 1 -C 4 alkyl.

5. The compound of formula (II) according to claim 4 or a pharmaceutically acceptable salt thereof, wherein R 3 is —(CR′R″)-phenyl, said phenyl is substituted by halogen, said R′ and R″ are each independently H or methyl.

6. The compound of formula (II) according to claim 5 or a pharmaceutically acceptable salt thereof, wherein R 3 is —(CR′R″)-phenyl, said phenyl is substituted by halogen, said R′, R″ are each independently H or methyl in (S) or (R) configuration.

7. The compound of formula (II) according to claim 3 or a pharmaceutically acceptable salt thereof, wherein R 1 is aryl, heteroaryl or nitrogen-containing saturated heterocyclyl, wherein said aryl, heteroaryl or nitrogen-containing saturated heterocyclyl is unsubstituted or substituted by halogen, C 1 -C 6 alkyl, C 1 -C 4 alkyl substituted by aryl, C 1 -C 6 alkoxy, C 3 -C 8 cycloalkyl, —NH 2 , —COR′″, —COOR′″, —SOOR′″ or —OH; said R′″ is H, C 1 -C 4 alkyl, C 1 -C 4 alkyl substituted by 1-3 halogen, aryl that is unsubstituted or substituted by halogen, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, —CN, —NH 2 or —OH, or heteroaryl that is unsubstituted or substituted by halogen, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, —CN, —NH 2 or —OH.

8. The compound according to claim 7 or a pharmaceutically acceptable salt thereof, wherein R 1 is nitrogen-containing saturated heterocyclyl, said nitrogen-containing saturated heterocyclyl is unsubstituted or substituted by halogen, C 1 -C 6 alkyl, C 1 -C 2 alkyl substituted by aryl, C 1 -C 6 alkoxy, —NH 2 , —COR′″, —COOR′″, —SOOR′″ or —OH; said R′″ is H, C 1 -C 4 alkyl, C 1 -C 4 alkyl substituted by 1-3 halogen, aryl that is unsubstituted or substituted by halogen, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, —CN, —NH 2 or —OH, or heteroaryl that is unsubstituted or substituted by halogen, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, —CN, —NH 2 or —OH.

9. The compound of formula (II) according to claim 8 or a pharmaceutically acceptable salt thereof, wherein R 1 is nitrogen-containing saturated heterocyclyl, said nitrogen-containing saturated heterocyclyl is unsubstituted or substituted by halogen, C 1 -C 4 alkyl, C 1 -C 2 alkyl substituted by phenyl, C 1 -C 4 alkoxy, —NH 2 , —COR′″, —COOR′″, —SOOR′″ or —OH; said R′″ is H, C 1 -C 4 alkyl, C 1 -C 4 alkyl substituted by 1-3 halogen, aryl that is unsubstituted or substituted by halogen, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, —CN, —NH 2 or —OH, or heteroaryl that is unsubstituted or substituted by halogen, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, —CN, —NH 2 or —OH.

10. The compound of formula (II) according to claim 9 or a pharmaceutically acceptable salt thereof, wherein R 1 is piperidyl, pyrrolidinyl, pyrazolidinyl, azetidinyl or morpholinyl, wherein said piperidyl, pyrrolidinyl, pyrazolidinyl, azetidinyl and morpholinyl is unsubstituted or substituted by halogen, C 1 -C 4 alkyl, C 1 -C 4 alkyl substituted by aryl, C 1 -C 4 alkoxy, —COR′″, —COOR′″, —SOOR′″, —NH 2 or —OH; said R′″ is H, C 1 -C 4 alkyl, C 1 -C 4 alkyl substituted by 1-3 halogen, aryl that is unsubstituted or substituted by halogen, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, —CN, —NH 2 or —OH, or heteroaryl that is unsubstituted or substituted by halogen, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, —CN, —NH 2 or —OH.

11. The compound of formula (II) according to claim 10 or a pharmaceutically acceptable salt thereof, wherein R 1 is piperidyl, said piperidyl is unsubstituted or substituted by C 1 -C 4 alkyl, —COR′″, —COOR′″, —SOOR′″ or C 1 -C 2 alkyl substituted by phenyl; said R′″ is H, C 1 -C 4 alkyl, C 1 -C 4 alkyl substituted by 1-3 halogen, phenyl that is unsubstituted or substituted by halogen, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, —CN, —NH 2 or —OH, thiazolyl that is unsubstituted or substituted by halogen, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, —CN, —NH 2 or —OH, imidazolyl that is unsubstituted or substituted by halogen, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, —CN, —NH 2 or —OH, pyridiyl that is unsubstituted or substituted by halogen, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, —CN, —NH 2 or —OH, or pyrazinyl that is unsubstituted or substituted by halogen, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, —CN, —NH 2 or —OH.

12. The compound of formula (II) according to claim 11 or a pharmaceutically acceptable salt thereof, wherein R 1 is piperidyl that is unsubstituted or substituted by C 1 -C 4 alkyl, C 1 -C 2 alkyl substituted by phenyl, —COR′″, —COOR′″ or —SOOR′″, said R′″ is C 1 -C 4 alkyl or phenyl substituted by halogen, C 1 -C 4 alkyl or —CN.

13. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, said compound is selected from:

3-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)-5-(1-(1-tert-butyl formatepiperidin-4-yl)-1H-1,2,3-triazol-4-yl)-2-aminopyridine;

3-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)-5-(1-(piperidin-4-yl)-1H-1,2,3-triazol-4-yl)-2-aminopyridine;

3-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)-5-(1-(1-benzylpiperidin-4-yl)-1H-1,2,3-triazol-4-yl)-2-aminopyridine;

3-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)-5-(1-(1-p-cyanobenzoylpiperidin-4-yl)-1H-1,2,3-triazol-4-yl)-2-aminopyridine;

3-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)-5-(1-(1-p-fluorobenzoylpiperidin-4-yl)-1H-1,2,3-triazol-4-yl)-2-aminopyridine;

3-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)-5-(1-(1-p-tosylpiperidin-4-yl)-1H-1,2,3-triazol-4-yl)-2-aminopyridine;

3-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)-5-(1-(1-mesylpiperidin-4-yl)-1H-1,2,3-triazol-4-yl)-2-aminopyridine;

3-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)-5-(1-(1-methylpiperidin-4-yl)-1H-1,2,3-triazol-4-yl)-2-aminopyridine;

3-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)-5-(1-((1-diphenylmethyl)azetidin-3-yl)-1H-1,2,3-triazol-4-yl)-2-aminopyridine;

3-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)-5-(1-(azetidin-3-yl)-1H-1,2,3-triazol-4-yl)-2-aminopyridine;

(S)—N-tert-butyloxycarbonyl-(4-(6-amino-5-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-3-yl)-1H-1,2,3-triazol-1-yl)piperidine;

(S)-3-(1-(2,6-dichloro-3-fluorophenylethoxy)-5-(1-(piperidin-4-yl)-1H-1,2,3-triazol-4-yl)-2-aminopyridine; and

(R)-3-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)-5-(1-(piperidin-4-yl)-1H-1,2,3-triazol-4-yl)-2-aminopyridine.

14. A pharmaceutical composition containing the compound according to claim 1 or a pharmaceutically acceptable salt thereof and pharmaceutically acceptable carriers.

15. A method for treating a tumor, comprising administering to a subject in need thereof an effective amount of a compound according to claim 1 .

16. A method for preparing the compound of formula (II) according to claim 2 , including the steps of:

wherein R 1 and R 3 have the same meaning as those in claim 2 ;

3-hydroxy-2-nitropyridine, as the starting material, is reacted with compound (b) via nucleophilic substitution to yield compound (c); the compound (c) is converted to compound (e) via reduction, bromination; the compound (e) and trimethylsilylethyne are converted to compound (f) under the catalysis of a transition metal catalyst; the compound (f) is converted to compound (g) under the effect of a base; the compound (g) is reacted with organic azide (i) under the catalysis of a metal catalyst to yield the final product, i.e. the compound of general formula (II).