Claims for Patent: 9,487,491

Summary for Patent: 9,487,491

Title:	Diamino heterocyclic carboxamide compound
Abstract:	Provided is a compound useful as an inhibitor against the kinase activity of EML4-ALK fusion protein. As a result of intensive and extensive studies on compounds having inhibitory activity against the kinase activity of EML4-ALK fusion protein, the present inventors found that the diamino heterocyclic carboxamide compounds of the present invention had inhibitory activity against the kinase activity of EML4-ALK fusion protein. By this finding, the present invention was completed. The compounds of the present invention can be used as a pharmaceutical composition for preventing and/or treating cancer, such as lung cancer, non-small cell lung cancer, and small cell lung cancer.
Inventor(s):	Shimada; Itsuro (Chuo-ku, JP), Kurosawa; Kazuo (Chuo-ku, JP), Matsuya; Takahiro (Chuo-ku, JP), Iikubo; Kazuhiko (Chuo-ku, JP), Kondoh; Yutaka (Chuo-ku, JP), Kamikawa; Akio (Chuo-ku, JP), Tomiyama; Hiroshi (Chuo-ku, JP), Iwai; Yoshinori (Chuo-ku, JP)
Assignee:	ASTELLAS PHARMA INC. (Tokyo, JP) KOTOBUKI PHARMACEUTICAL CO., LTD. (Nagano, JP)
Application Number:	14/472,959
Patent Claims:	1. A method for treating non-small cell lung cancer, which comprises administering to a patient in need thereof an effective amount of a 6-ethyl-3-({3-methoxy-4-[4-(4methylpiperazin-1-yl)piperidin-1 -yl]phenyl}amino)-5-(tetrahydro-2H-pyran-4-ylamino)pyrazine-2-carboxamide or a salt thereof. 2. The method according to claim 1, which comprises administering a fumaric acid salt of 6-ethyl-3-({3-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}- amino)-5-(tetrahydro-2H-pyran-4-ylamino) pyrazine-2-carboxamide. 3. The method according to claim 1, which comprises administering 6-ethyl-3-({3-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1 - yl]phenyl}amino)-5-(tetrahydro-2H-pyran-4-ylamino)pyrazine-2-carboxamide hemifumarate (HFM). 4. The method according to claim 1, wherein said administration is oral administration. 5. The method according to claim 4, wherein said 6-ethyl-3-({3-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}- amino)-5 -(tetrahydro-2H-pyran-4-ylamino)pyrazine-2-carboxamide or salt thereof is administered in a daily amount of 0.01 to 10 mg/kg of body weight of said patient. 6. The method according to claim 2, wherein said administration is oral administration. 7. The method according to claim 6, wherein said fumaric acid salt of 6-ethyl-3-({3-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1 -yl]phenyl}amino)-5-(tetrahydro-2H-pyran-4-ylamino)pyrazine-2-carboxamide or salt thereof is administered in a daily amount of 0.01 to 10 mg/kg of body weight of said patient. 8. The method according to claim 3, wherein said administration is oral administration. 9. The method according to claim 8, wherein said 6-ethyl-3-({3-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}- amino)-5 -(tetrahydro-2H-pyran-4-ylamino)pyrazine-2-carboxamide hemifumarate (HFM) is administered in a daily amount of 0.01 to 10 mg/kg of body weight of said patient. 10. A method for treating acute myelocytic leukemia or atypical chronic myelocytic leukemia, which comprises administering to a patient in need thereof an effective amount of 6-ethyl-3-({3 -methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}amino)-5-(tet- rahydro-2H-pyran-4-ylamino)pyrazine-2-carboxamide or a salt thereof. 11. The method of claim 10, wherein said acute myelocytic leukemia is mutant FLT3 polynucleotide-positive acute myelocytic leukemia, FLT3 internal tandem duplication (ITD) positive acute myelocytic leukemia, or acute myelocytic leukemia with FLT3 point mutation. 12. The method of claim 10, wherein said atypical chronic myelocytic leukemia is FLT3 fusion polynucleotide-positive atypical chronic myelocytic leukemia. 13. The method according to claim 10, which comprises administering a fumaric acid salt of 6-ethyl-3-({3-methoxy-4-[4-(4 -methylpiperazin-1-yl)piperidin-1-yl]phenyl}amino)-5-(tetrahydro-2H-pyran- -4 -ylamino)pyrazine-2-carboxamide. 14. The method according to claim 10, which comprises administering 6-ethyl-3-({3-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1 -yl]phenyl}amino)-5-(tetrahydro-2H-pyran-4-ylamino)pyrazine-2-carboxamide hemifumarate (HFM). 15. The method according to claim 10, wherein said administration is oral administration. 16. The method according to claim 15, wherein said 6-ethyl-3-({3-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}- amino)-5-(tetrahydro-2H-pyran-4-ylamino)pyrazine-2-carboxamide or salt thereof is administered in a daily amount of 0.01 to 10 mg/kg of body weight of said patient. 17. The method according to claim 13, wherein said administration is oral administration. 18. The method according to claim 17, wherein said fumaric acid salt of 6-ethyl-3-({3-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}- amino)-5-(tetrahydro-2H-pyran-4-ylamino)pyrazine-2-carboxamide or salt thereof is administered in a daily amount of 0.01 to 10 mg/kg of body weight of said patient. 19. The method according to claim 14, wherein said administration is oral administration. 20. The method according to claim 19, wherein said 6-ethyl-3-({3-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}- amino)-5-(tetrahydro-2H-pyran-4-ylamino)pyrazine-2-carboxamide hemifumarate (HFM) is administered in a daily amount of 0.01 to 10 mg/kg of body weight of said patient. 21. The method according to claim 11, which comprises administering a fumaric acid salt of 6-ethyl-3-({3-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}- amino)-5-(tetrahydro-2H-pyran-4-ylamino)pyrazine-2-carboxamide. 22. The method according to claim 11, which comprises administering 6-ethyl-3-({3-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}- amino)-5-(tetrahydro-2H-pyran-4-ylamino)pyrazine-2-carboxamide hemifumarate (HFM). 23. The method according to claim 21, wherein said administration is oral administration. 24. The method according to claim 23, wherein said fumaric acid salt of 6-ethyl-3-({3-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}- amino)-5-(tetrahydro-2H-pyran-4-ylamino)pyrazine-2-carboxamide is administered in a daily amount of 0.01 to 10 mg/kg of body weight of said patient. 25. The method according to claim 22, wherein said administration is oral administration. 26. The method according to claim 25, wherein said 6-ethyl-3-({3-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}- amino)-5-(tetrahydro-2H-pyran-4-ylamino)pyrazine-2-carboxamide hemifumarate (HFM) is administered in a daily amount of 0.01 to 10 mg/kg of body weight of said patient.