Heteroaryl derivative, method for producing same, and pharmaceutical composition comprising same as effective component
The present invention relates to a 6-(isooxazolidin-2-yl)-N-phenylpyrimidin-4-amine derivative, and a pharmaceutical composition for preventing or treating cancer comprising the compound as an effective component. The compound exhibits high inhibitory activity against an epidermal growth factor receptor (EGFR) variant, or wild-type or variants of one or more of ERBB2 and ERBB4, and thus may be usefully used in the treatment of cancers in which same are expressed. In particular, the compound exhibits excellent inhibitory activity on proliferation of lung cancer cell lines, and thus can be usefully used in the treatment of lung cancer.
1. A compound of Formula 8,
wherein:
R 5 is C 1 -8 alkyl, aryl of 3 to 12 atoms, heteroaryl of 3 to 12 atoms, or heterocycloalkyl of 3 to 12 atoms, wherein the C 1-8 alkyl, aryl, heteroaryl, and heterocycloalkyl are independently unsubstituted or substituted by at least one substituent J;
J is selected from the group consisting of halogen, cyano, C 1-8 alkyl substituted or unsubstituted by halogen, aryl of 3 to 12 atoms, heteroaryl of 3 to 12 atoms, heterocycloalkyl of 3 to 12 atoms, C 2-8 alkenyl, C 1-8 alkoxy, C 2-8 alkynyl and C 1-8 alkylamino, wherein each of the substituents J are independently unsubstituted or substituted with one or more substituents selected from the group consisting of halogen, C 1-8 alkyl substituted or unsubstituted by halogen, C 1-8 alkoxy, and C 1-8 alkylamino;
R 6 is hydrogen or C 1-8 alkyl; and
G is halogen, a sulfonic acid, an ester, or an alkoxy.
2. The compound according to claim 1 , wherein R 5 is C 1-8 alkyl unsubstituted or substituted by at least one substituent J.
3. The compound according to claim 1 , wherein R 5 is aryl of 3 to 12 atoms unsubstituted or substituted by at least one substituent J.
4. The compound according to claim 3 , wherein R 5 is phenyl unsubstituted or substituted by at least one substituent J.
5. The compound according to claim 4 , wherein J is selected from the group consisting of halogen, cyano, C 1-8 alkyl substituted and unsubstituted by halogen, C 2-8 alkenyl, and C 1-8 alkoxy.
6. The compound according to claim 5 , wherein J is halogen.
7. The compound according to claim 6 , wherein the halogen is selected from the group consisting of fluoro and chloro.
8. The compound according to claim 7 , wherein the halogen is fluoro.
9. The compound according to claim 7 , wherein the halogen is chloro.
10. The compound according to claim 5 , wherein J is cyano.
11. The compound according to claim 5 , wherein J is C 1-8 alkyl substituted or unsubstituted by halogen.
12. The compound according to claim 11 , wherein J is —CF 3 .
13. The compound according to claim 5 , wherein J is C 2-8 alkenyl.
14. The compound according to claim 5 , wherein J is C 1-8 alkoxy.
15. The compound according to claim 14 , wherein C 1-8 alkoxy is —OCH 3 .
16. The compound according to claim 1 , wherein the compound is
17. The compound according to claim 1 , wherein R 5 is heteroaryl of 3 to 12 atoms unsubstituted or substituted by at least one substituent J.
18. The compound according to claim 17 , wherein J is selected from the group consisting of halogen, cyano, C 1-8 alkyl substituted and unsubstituted by halogen, C 2-8 alkenyl, and C 1-8 alkoxy.
19. The compound according to claim 18 , wherein J is halogen.
20. The compound according to claim 19 , wherein the halogen is selected from the group consisting of fluoro and chloro.
21. The compound according to claim 20 , wherein the halogen is fluoro.
22. The compound according to claim 20 , wherein the halogen is chloro.
23. The compound according to claim 18 , wherein J is cyano.
24. The compound according to claim 18 , wherein J is C 1-8 alkyl substituted or unsubstituted by halogen.
25. The compound according to claim 24 , wherein J is —CF 3 .
26. The compound according to claim 18 , wherein J is C 2-8 alkenyl.
27. The compound according to claim 18 , wherein J is C 1-8 alkoxy.
28. The compound according to claim 27 , wherein C 1-8 alkoxy is —OCH 3 .
29. The compound according to claim 1 , wherein R 5 is heterocycloalkyl of 3 to 12 atoms unsubstituted or substituted by at least one substituent J.