IP Library › Granted Patent US 9,187,489
Granted Patent B2
US 9,187,489 · App. 14/378,318 · Granted Nov 17, 2015

Imidazo[1,2-b]pyridazine derivatives as kinase inhibitors

Inventors: Yasuyuki Takeda (Shinagawa-ku, JP); Kenji Yoshikawa (Shinagawa-ku, JP); Yoshiko Kagoshima (Shinagawa-ku, JP); Yuko Yamamoto (Shinagawa-ku, JP); Ryoichi Tanaka (Shinagawa-ku, JP); Yuichi Tominaga (Shinagawa-ku, JP); Masaki Kiga (Shinagawa-ku, JP); Yoshito Hamada (Shinagawa-ku, JP)
Assignee: Daiichi Sankyo Company, Limited
C07D487/04
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 9,187,489
App. No.
14/378,318
Granted
Nov 17, 2015
Kind
B2
Abstract

The present invention is intended to provide a compound or a pharmacologically acceptable salt thereof which is useful in the treatment of a tumor through its ROS1 kinase enzyme activity inhibitory effect and NTRK kinase enzyme inhibitory effect. The present invention provides a compound having an imidazo[1,2-b]pyridazine structure represented by the general formula (I) or a pharmacologically acceptable salt thereof, and a pharmaceutical composition comprising the compound. In the formula, R 1 , G, T, Y 1 , Y 2 , Y 3 , and Y 4 are as defined herein.

Claims (44)

1. A compound selected from the following group or a pharmacologically acceptable salt thereof:

N-[(1R)-1-(3-fluorophenyl)ethyl]-3-[4-[[(2S)-pyrrolidin-2-yl]methoxy]phenyl]imidazo[1,2-b]pyridazin-6-amine,

N-[(1R)-1-(3-fluorophenyl)ethyl]-3-[4-[2-(methylamino)ethoxy]phenyl]imidazo[1,2-b]pyridazin-6-amine,

3-[4-[[(2S)-azetidin-2-yl]methoxy]phenyl]-N-[(1R)-1-(3-fluorophenyl)ethyl]imidazo[1,2-b]pyridazin-6-amine,

3-[4-[(2R)-2-aminopropoxy]phenyl]-N-[(1R)-1-(3-fluorophenyl)ethyl]imidazo[1,2-b]pyridazin-6-amine,

3-[4-[(2S)-2-aminopropoxy]phenyl]-N-[(1R)-1-(3-fluorophenyl)ethyl]imidazo[1,2-b]pyridazin-6-amine,

(4S)-4-amino-1-[4-[6-[(1R)-1-(3-fluorophenyl)ethoxy]imidazo[1,2-b]pyridazin-3-yl]phenyl]pyrrolidin-2-one,

(4S)-4-amino-1-[4-[6-[[(1R)-1-(3-fluorophenyl)ethyl]amino]imidazo[1,2-b]pyridazin-3-yl]phenyl]pyrrolidin-2-one,

(4S)-4-amino-1-[4-[6-[(3-fluorophenyl)methyl-methylamino]imidazo[1,2-b]pyridazin-3-yl]phenyl]pyrrolidin-2-one, and

(4S)-4-amino-1-[4-[6-[(3-fluorophenyl)methyl-methylamino]imidazo[1,2-b]pyridazin-3-yl]-3-methoxyphenyl]pyrrolidin-2-one.

2. N-[(1R)-1-(3-Fluorophenyl)ethyl]-3-[4-[[(2S)-pyrrolidin-2-yl]methoxy]phenyl]imidazo[1,2-b]pyridazin-6-amine.

3. 3-[4-[(2R)-2-Aminopropoxy]phenyl]-N-[(1R)-1-(3-fluorophenyl)ethyl]imidazo[1,2-b]pyridazin-6-amine.

4. (4S)-4-Amino-1-[4-[6-[(1R)-1-(3-fluorophenyl)ethoxy]imidazo[1,2-b]pyridazin-3-yl]phenyl]pyrrolidin-2-one.

5. (4S)-4-Amino-1-[4-[6-[(3-fluorophenyl)methyl-methylamino]imidazo[1,2-b]pyridazin-3-yl]phenyl]pyrrolidin-2-one.

6. N-[(1R)-1-(3-Fluorophenyl)ethyl]-3-[4-[[(2S)-pyrrolidin-2-yl]methoxy]phenyl]imidazo[1,2-b]pyridazin-6-amine maleate.

7. N-[(1R)-1-(3-Fluorophenyl)ethyl]-3-[4-[[(2S)-pyrrolidin-2-yl]methoxy]phenyl]imidazo[1,2-b]pyridazin-6-amine adipate.

8. 3-[4-[(2R)-2-Aminopropoxy]phenyl]-N-[(1R)-1-(3-fluorophenyl)ethyl]imidazo[1,2-b]pyridazin-6-amine methanesulfonate.

9. 3-[4-[(2R)-2-Aminopropoxy]phenyl]-N-[(1R)-1-(3-fluorophenyl)ethyl]imidazo[1,2-b]pyridazin-6-amine adipate.

10. (4S)-4-Amino-1-[4-[6-[(1R)-1-(3-fluorophenyl)ethoxy]imidazo[1,2-b]pyridazin-3-yl]phenyl]pyrrolidin-2-one benzenesulfonate.

11. (4S)-4-Amino-1-[4-[6-[(1R)-1-(3-fluorophenyl)ethoxy]imidazo[1,2-b]pyridazin-3-yl]phenyl]pyrrolidin-2-one hydrochloride.

12. (4S)-4-Amino-1-[4-[6-[(1R)-1-(3-fluorophenyl)ethoxy]imidazo[1,2-b]pyridazin-3-yl]phenyl]pyrrolidin-2-one adipate.

13. (4S)-4-Amino-1-[4-[6-[(1R)-1-(3-fluorophenyl)ethoxy]imidazo[1,2-b]pyridazin-3-yl]phenyl]pyrrolidin-2-one lactate.

14. (4S)-4-Amino-1-[4-[6-[(1R)-1-(3-fluorophenyl)ethoxy]imidazo[1,2-b]pyridazin-3-yl]phenyl]pyrrolidin-2-one benzoate.

15. (4S)-4-Amino-1-[4-[6-[(3-fluorophenyl)methyl-methylamino]imidazo[1,2-b]pyridazin-3-yl]phenyl]pyrrolidin-2-one benzenesulfonate.

16. (4S)-4-Amino-1-[4-[6-[(3-fluorophenyl)methyl-methylamino]imidazo[1,2-b]pyridazin-3-yl]phenyl]pyrrolidin-2-one adipate.

17. (4S)-4-Amino-1-[4-[6-[(3-fluorophenyl)methyl-methylamino]imidazo[1,2-b]pyridazin-3-yl]phenyl]pyrrolidin-2-one camphorate.

18. A pharmaceutical composition comprising a compound according to claim 9 as an active ingredient.

19. A method for inhibiting proliferation of a cancer cell having a detectable increase in the expression level of ROS1 gene, comprising administering a compound according to claim 9 as an active ingredient.

20. A method for inhibiting proliferation of a cancer cell having a detectable increase in the expression level of NTRK gene, comprising a compound according to claim 9 as an active ingredient.

21. A method for inhibiting proliferation of a cancer cell having a detectable expression of ROS1 fusion gene, comprising administering a compound according to claim 9 .

22. A method for inhibiting proliferation of a cancer cell having a detectable expression of NTRK fusion gene, comprising administering a compound according to claim 9 .

23. A method for inhibiting proliferation of a cancer cell by the inhibition of ROS1 kinase enzyme activity, comprising administering a compound according to claim 9 .

24. A method for inhibiting proliferation of a cancer cell by the inhibition of NTRK kinase enzyme activity, comprising a compound according to claim 1 or a pharmacologically acceptable salt thereof as an active ingredient.

25. A method for inhibiting ROS1 kinase enzyme activity in a subject, comprising administering a compound according to claim 9 .

26. A method for inhibiting NTRK kinase enzyme activity in a subject, comprising administering a compound according to claim 9 .

27. A pharmaceutical composition comprising a compound according to claim 3 or a pharmacologically acceptable salt thereof as an active ingredient.

28. A method for inhibiting proliferation of a cancer cell having a detectable increase in the expression level of ROS1 gene, comprising administering a compound according to claim 3 or a pharmacologically acceptable salt thereof as an active ingredient.

29. A method for inhibiting proliferation of a cancer cell having a detectable increase in the expression level of NTRK gene, comprising a compound according to claim 3 or a pharmacologically acceptable salt thereof as an active ingredient.

30. A method for inhibiting proliferation of a cancer cell having a detectable expression of ROS1 fusion gene, comprising administering a compound according to claim 3 or a pharmacologically acceptable salt thereof.

31. A method for inhibiting proliferation of a cancer cell having a detectable expression of NTRK fusion gene, comprising administering a compound according to claim 3 or a pharmacologically acceptable salt thereof.

32. A method for inhibiting proliferation of a cancer cell by the inhibition of ROS1 kinase enzyme activity, comprising administering a compound according to claim 3 or a pharmacologically acceptable salt thereof.

33. A method for inhibiting proliferation of a cancer cell by the inhibition of NTRK kinase enzyme activity, comprising a compound according to claim 3 or a pharmacologically acceptable salt thereof as an active ingredient.

34. A method for inhibiting ROS1 kinase enzyme activity in a subject, comprising administering a compound according to claim 3 or a pharmacologically acceptable salt thereof.

35. A method for inhibiting NTRK kinase enzyme activity in a subject, comprising administering a compound according to claim 3 or a pharmacologically acceptable salt thereof.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 13, 2014
From: TAKEDA, YASUYUKI; YOSHIKAWA, KENJI; KAGOSHIMA, YOSHIKO; YAMAMOTO, YUKO; TANAKA, RYOICHI; TOMINAGA, YUICHI; KIGA, MASAKI; HAMADA, YOSHITO
To: DAIICHI SANKYO COMPANY, LIMITED
Reel/Frame 033529/0750 →
Priority Claims (1)
JP 2012-127079 · Jun 4, 2012 · national
Continuity (1)
Related Publication 20150051190A1 · Feb 19, 2015