Claims for Patent: 10,159,662

Summary for Patent: 10,159,662

Title:	Azetidine derivative, preparation method therefor, and use thereof
Abstract:	The present invention relates to an azetidine derivative for use as a Janus kinase (JAK) inhibitor, a drug composition comprising same, a preparation method therefor, and a use thereof in the treatment of JAK-related diseases comprising, for example, inflammatory diseases, autoimmune diseases, and cancers.
Inventor(s):	Xie; Yinong (Chengdu, CN), You; Zejin (Chengdu, CN), Deng; Zhiwen (Chengdu, CN), Zhu; Jun (Chengdu, CN), Wang; Ao (Chengdu, CN), Feng; Yan (Chengdu, CN), Long; Dong (Chengdu, CN), Zeng; Hong (Chengdu, CN), Song; Hongmei (Chengdu, CN), Ye; Qijun (Chengdu, CN), Qi; Wei (Chengdu, CN), Su; Donghai (Chengdu, CN), Wang; Lichun (Chengdu, CN), Wang; Jingyi (Chengdu, CN)
Assignee:	SICHUAN KELUN-BIOTECH BIOPHARMACEUTICAL CO., LTD. (Chengdu, CN)
Application Number:	15/767,508
Patent Claims:	1. A compound of Formula I or a pharmaceutically acceptable salt, stereoisomer, polymorph, or solvate thereof: ##STR00115## wherein: R.sub.1 is selected from the group consisting of C.sub.1-6 alkyl, C.sub.3-10 cycloalkyl, 3- to 10-membered heterocyclyl, C.sub.6-14 aryl, 5- to 14-membered heteroaryl, C.sub.7-20 aralkyl, C(O)R.sub.10, and S(O).sub.2R.sub.11; R.sub.2 and R.sub.3 are each independently selected from the group consisting of H, CN, halogen, and C.sub.1-6 alkyl; R.sub.4 and R.sub.5 are each independently selected from group consisting of H, halogen, and CN; X is CR.sub.6; Y is selected from the group consisting of N and CR.sub.9; Z is selected from the group consisting of N and CR.sub.7; W is selected from the group consisting of N and CR.sub.8; R.sub.6, R.sub.7, R.sub.8 and R.sub.9 are each independently selected from the group consisting of H, halogen, CN, C.sub.1-6 alkyl, C.sub.1-6 alkoxyl, and C(O)NR.sub.12R.sub.13; R.sub.10 and R.sub.11 are each independently selected from the group consisting of C.sub.1-6 alkyl, C.sub.3-10 cycloalkyl, 3- to 10-membered heterocyclyl, C.sub.6-14 aryl, 5- to 14-membered heteroaryl, C.sub.7-20 aralkyl, and NR.sub.12R.sub.13; R.sub.12 and R.sub.13 are each independently selected from the group consisting of H and C.sub.1-6 alkyl; wherein the above alkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl and aralkyl are each optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of halogen, CN, and C.sub.1-4 alkyl. 2. The compound according to claim 1, or a pharmaceutically acceptable salt, stereoisomer, polymorph, or solvate thereof, wherein the compound is a compound of Formula II: ##STR00116## 3. The compound according to claim 2, or a pharmaceutically acceptable salt, stereoisomer, polymorph, or solvate thereof, wherein the compound is a compound of Formula IV: ##STR00117## wherein: R.sub.1 is selected from the group consisting of C(O)R.sub.10 and S(O).sub.2R.sub.11; R.sub.10 and R.sub.11 are each independently selected from the group consisting of C.sub.1-6 alkyl, C.sub.3-10 cycloalkyl, 3- to 10-membered heterocyclyl, C.sub.6-14 aryl, 5- to 14-membered heteroaryl, C.sub.7-20 aralkyl, and NR.sub.12R.sub.13, wherein the alkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl and aralkyl are each optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of halogen, CN, and C.sub.1-4 alkyl. 4. The compound according to claim 3, or a pharmaceutically acceptable salt, stereoisomer, polymorph, or solvate thereof, wherein the compound is a compound of Formula V: ##STR00118## 5. The compound according to claim 4, or a pharmaceutically acceptable salt, stereoisomer, polymorph, or solvate thereof, wherein the compound is a compound of Formula VI: ##STR00119## 6. A compound or a pharmaceutically acceptable salt, stereoisomer, polymorph, or solvate thereof, wherein the compound is selected from the group consisting of: ##STR00120## ##STR00121## ##STR00122## ##STR00123## ##STR00124## ##STR00125## ##STR00126## ##STR00127## ##STR00128## ##STR00129## ##STR00130## ##STR00131## ##STR00132## 7. A pharmaceutical composition, comprising a therapeutically effective amount of the compound according to claim 1 and one or more pharmaceutically acceptable carriers. 8. The pharmaceutical composition according to claim 7, wherein the therapeutically effective amount is a range of about 0.01 mg to about 1000 mg. 9. The pharmaceutical composition according to claim 7, further comprising one or more additional drugs. 10. The pharmaceutical composition according to claim 9, wherein the additional drug(s) is one or more selected from the group consisting of efalizumab, mycophenolate sodium, etanercept, and methotrexate. 11. A method for the treatment of a JAK-related disease, comprising administering to a subject in need thereof a therapeutically effective amount of the compound according to claim 1, wherein the JAK-related disease is rheumatoid arthritis. 12. A pharmaceutical composition, comprising a therapeutically effective amount of the compound according to claim 3 and one or more pharmaceutically acceptable carriers. 13. The pharmaceutical composition according to claim 12, wherein the therapeutically effective amount is a range of about 0.01 mg to about 1000 mg. 14. The pharmaceutical composition according to claim 12, further comprising one or more additional drugs. 15. The pharmaceutical composition according to claim 14, wherein the additional drug(s) is one or more selected from the group consisting of efalizumab, mycophenolate sodium, etanercept, and methotrexate. 16. A method for the treatment of a JAK-related disease, comprising administering to a subject in need thereof a therapeutically effective amount of the compound according to claim 3, wherein the JAK-related disease is rheumatoid arthritis. 17. A pharmaceutical composition, comprising a therapeutically effective amount of the compound according to claim 6 and one or more pharmaceutically acceptable carriers. 18. The pharmaceutical composition according to claim 17, wherein the therapeutically effective amount is a range of about 0.01 mg to about 1000 mg. 19. The pharmaceutical composition according to claim 17, further comprising one or more additional drugs. 20. The pharmaceutical composition according to claim 19, wherein the additional drug(s) is one or more selected from the group consisting of efalizumab, mycophenolate sodium, etanercept, and methotrexate. 21. A method for the treatment of a JAK-related disease, comprising administering to a subject in need thereof a therapeutically effective amount of the compound according to claim 6, wherein the JAK-related disease is rheumatoid arthritis. 22. A method for the treatment of a JAK-related disease, comprising administering to a subject in need thereof a therapeutically effective amount of the pharmaceutical composition according to claim 7, wherein the JAK-related disease is rheumatoid arthritis. 23. A method for the treatment of a JAK-related disease, comprising administering to a subject in need thereof a therapeutically effective amount of the pharmaceutical composition according to claim 12, wherein the JAK-related disease is rheumatoid arthritis. 24. A method for the treatment of a JAK-related disease, comprising administering to a subject in need thereof a therapeutically effective amount of the pharmaceutical composition according to claim 17, wherein the JAK-related disease is rheumatoid arthritis. 25. The pharmaceutical composition according to any of claim 8, 13 or 18, wherein the therapeutically effective amount is 0.1-500 mg. 26. The pharmaceutical composition according to any of claim 8, 13 or 18, wherein the therapeutically effective amount is 0.5-300 mg. 27. The pharmaceutical composition according to any of claim 8, 13 or 18, wherein the therapeutically effective amount is 1-150 mg. 28. The pharmaceutical composition according to any of claim 8, 13 or 18, wherein the therapeutically effective amount is 1-50 mg. 29. The pharmaceutical composition according to any of claim 8, 13 or 18, wherein the therapeutically effective amount is 1.5 mg. 30. The pharmaceutical composition according to any of claim 8, 13 or 18, wherein the therapeutically effective amount is 2 mg. 31. The pharmaceutical composition according to any of claim 8, 13 or 18, wherein the therapeutically effective amount is 4 mg. 32. The pharmaceutical composition according to any of claim 8, 13 or 18, wherein the therapeutically effective amount is 10 mg. 33. The pharmaceutical composition according to any of claim 8, 13 or 18, wherein the therapeutically effective amount is 25 mg.

Details for Patent 10,159,662

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Immunex Corporation	ENBREL	etanercept	For Injection	103795	11/02/1998		2035-12-11
Immunex Corporation	ENBREL	etanercept	For Injection	103795	05/27/1999		2035-12-11
Immunex Corporation	ENBREL	etanercept	Injection	103795	09/27/2004		2035-12-11