Azetidine derivative, preparation method therefor, and use thereof

Patent metadata

Field	Value
Publication number	US-11045455-B2
Application number	US-202016745206-A
Country	US
Kind code	B2
Filing date	Jan 16, 2020
Priority date	Dec 11, 2015
Publication date	Jun 29, 2021
Grant date	Jun 29, 2021

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.

First claim

What is claimed is:

1. A method for treating psoriasis, the method comprising: administering to a subject in need thereof a therapeutically effective amount of a compound having Formula IV or a pharmaceutically acceptable salt, stereoisomer, polymorph, or solvate thereof:

wherein:
R 1 is selected from the group consisting of C(O)R 10 , and S(O) 2 R 11 ;
R 2 and R 3 are each independently selected from the group consisting of H, CN, halogen, and C 1-6 alkyl;
R 4 and R 5 are each independently selected from the group consisting of H, halogen, and CN;
Y is selected from the group consisting of N and CR 9 ;
Z is selected from the group consisting of N and CR 7 ;
W is selected from the group consisting of N and CR 8 ;
R 6 , R 7 , R 8 and R 9 are each independently selected from the group consisting of H, halogen, CN, C 1-6 alkyl, C 1-6 alkoxyl, and C(O)NR 12 R 13 ;
R 10 and R 11 are each independently selected from the group consisting of C 1-6 alkyl, C 3-10 cycloalkyl, and NR 12 R 13 ;
R 12 and R 13 are each independently selected from the group consisting of H and C 1-6 alkyl;
wherein the above alkyl, and cycloalkyl are each optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of halogen, CN, and alkyl.

2. The method according to claim 1 , wherein the compound is a compound of Formula V:

3. The method according to claim 1 , wherein the compound is a compound of Formula VI:

4. A method for treating psoriasis as in claim 1 , the method comprising:
administering to a subject in need thereof a therapeutically effective amount of a compound selected from the group consisting of:

or a pharmaceutically acceptable salt, stereoisomer, polymorph, or solvate thereof.

5. The method according to claim 1 , wherein the therapeutically effective amount is a member selected from the group consisting of about 0.01 mg to about 1000 mg, about 0.1-500 mg, about 0.5-300 mg, about 1-150 mg, about 1-50 mg or about 25 mg.

6. The method according to claim 1 , wherein the therapeutically effective amount is a member selected from the group consisting of about 0.1 mg, about 0.25 mg, about 0.5 mg, about 1 mg, about 1.5 mg, about 2 mg, about 3 mg, about 4 mg, about 5 mg, about 6 mg, about 8 mg or about 10 mg.

7. The method according to claim 1 , wherein the therapeutically effective amount is a member selected from the group consisting of about 0.1 mg, about 0.25 mg, about 0.5 mg, about 1 mg, about 1.5 mg, about 2 mg, about 3 mg, about 4 mg, about 5 mg or about 6 mg.

8. The method according to claim 4 , wherein the therapeutically effective amount is a member selected from the group consisting of about 0.01 mg to about 1000 mg, about 0.1-500 mg, about 0.5-300 mg, about 1-150 mg, about 1-50 mg or about 25 mg.

9. The method according to claim 4 , wherein the therapeutically effective amount is a member selected from the group consisting of about 0.1 mg, about 0.25 mg, about 0.5 mg, about 1 mg, about 1.5 mg, about 2 mg, about 3 mg, about 4 mg, about 5 mg, about 6 mg, 8 mg or about 10 mg.

10. The method according to claim 4 , wherein the therapeutically effective amount is a member selected from the group consisting of about 0.1 mg, about 0.25 mg, about 0.5 mg, about 1 mg, about 1.5 mg, about 2 mg, about 3 mg, about 4 mg, about 5 mg or about 6 mg.

11. The method according to claim 4 , wherein administering to a subject in need thereof a therapeutically effective amount of the compound

12. The method according to claim 11 , wherein the therapeutically effective amount is a member selected from the group consisting of about 0.01 mg to about 1000 mg, about 0.1-500 mg, about 0.5-300 mg, about 1-150 mg, about 1-50 mg or about 25 mg.

13. The method according to claim 11 , wherein the therapeutically effective amount is a member selected from the group consisting of about 0.1 mg, about 0.25 mg, about 0.5 mg, about 1 mg, about 1.5 mg, about 2 mg, about 3 mg, about 4 mg, about 5 mg, about 6 mg, 8 mg or about 10 mg.

14. The method according to claim 11 , wherein the therapeutically effective amount is a member selected from the group consisting of about 0.1 mg, about 0.25 mg, about 0.5 mg, about 1 mg, about 1.5 mg, about 2 mg, about 3 mg, about 4 mg, about 5 mg or about 6 mg.

15. The method according to claim 1 , wherein administration is via a route, which is a member selected from the group consisting of injection, intravenous, intraarterially, subcutaneous, intraperitoneal, intramuscular, transdermal, oral, buccal, nasal, transmucosal, topical, and inhalation.

Assignees

• Sichuan Kelun Biotech Biopharmaceutical Co Ltd

Inventors

• Xie Yinong
• You Zejin
• Deng Zhiwen
• Zhu Jun
• Wang Ao
• Feng Yan
• Long Dong
• Zeng Hong
• Song Hongmei
• Ye Qijun
• Qi Wei
• Su Donghai
• Wang Lichun
• Wang Jingyi

Classifications

• A61K31/519

  ortho- or peri-condensed with heterocyclic rings · CPC title

• C07D471/04

  Ortho-condensed systems · CPC title

• A61K2300/00

  Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00 · CPC title

• A61K31/343

  condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone · CPC title

• A61K38/1793

  for cytokines; for lymphokines; for interferons · CPC title