Imidazolonylquinolines and the use thereof as ATM kinase inhibitors

• US 10,457,677 B2
• Filed: 03/31/2016
• Issued: 10/29/2019
• Est. Priority Date: 04/02/2015
• Status: Active Grant

• Current Assignee: Merck Patent GmbH (Merck & Co., Inc.)
• Original Assignee: Merck Patent GmbH (Merck & Co., Inc.)
• Inventors: Fuchss, Thomas, Schiemann, Kai
• Primary Examiner(s): Moore, Susanna
• Application Number:
  US15/563,680
• Publication Number:
  US 20180072715A1
• Time in Patent Office: 1,307 Days
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/4375 the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07D 471/04 Ortho-condensed systems
• CPC Class Codes: C07D 519/00 Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00

Abstract

Compounds of the formula (I), which are ATM kinase inhibitors and can be employed, inter alia, for the treatment of cancer.

Claims

1. A method for the sensitisation of cancer cells to an anticancer agent or ionising radiation or a combination thereof, comprising administering to a subject in need thereof an effective amount of a compound of formula (IV) or a pharmaceutically acceptable salt, solvate, tautomer or stereoisomer thereof,

2. The method according to claim 1, wherein Het¹ is 1H-pyrazol-4-yl, 2H-pyrazol-3-yl, 1H-pyrazol-3-yl, 1-methyl-1H-pyrazol-4-yl, 3-methyl-1H-pyrazol-4-yl, 5-methyl-1H-pyrazol-3-yl, 4-methyl-1H-pyrazol-3-yl, 1-fluoro-methyl-1H-pyrazol-4-yl, 1 -difluoromethyl- 1H-pyrazol-4-yl, 1,3 -dimethyl- 1H-pyrazol-4-yl, 1-ethyl-1H-pyrazol-4-yl, 1 -ethyl-3 -methyl-1H-pyrazolyl, or 3 -fluoro- 1-methyl-1H-pyrazol-4-yl.

4. The method according to claim 1, wherein the compound of formula (IV) or a pharmaceutically acceptable salt thereof is administered.

24. The method according to claim 1, which is for the sensitisation of cancer cells to an anticancer agent.

25. The method according to claim 1, which is for the sensitisation of cancer cells to ionising radiation.

26. The method according to claim 1, which is for the sensitisation of cancer cells to a combination of an anticancer agent and ionising radiation.

27. The method according to claim 1, wherein a solvate of a compound of formula (IV) is administered.

28. The method according to claim 1, wherein the compound of formula (IV) contains one or more deuterium atoms.

29. The method according to claim 1, wherein the compound of formula (IV) does not contain a deuterium atom.

3. A method for the sensitisation of cancer cells to an anticancer agent or ionising radiation or a combination thereof, comprising administering to a subject in need thereof an effective amount of one of the following compounds or a pharmaceutically acceptable salt, solvate, tautomer or stereoisomer thereof

5. The method according to claim 3, wherein one of the following compounds or a pharmaceutically acceptable salt thereof is administered:

6. The method according to claim 3, wherein the following compound is administered

7. The method according to claim 3, wherein the following compound is administered

8. The method according to claim 3, wherein the following compound is administered

9. The method according to claim 3, wherein the following compound is administered

10. The method according to claim 3, wherein the following compound is administered

11. The method according to claim 3, wherein the following compound is administered

12. The method according to claim 3, wherein the following compound is administered

13. The method according to claim 3, wherein the following compound is administered

14. The method according to claim 3, wherein the following compound is administered

15. The method according to claim 3, wherein the following compound is administered

16. The method according to claim 3, wherein the following compound is administered

17. The method according to claim 3, wherein the following compound is administered

18. The method according to claim 3, wherein the following compound is administered

19. The method according to claim 3, wherein the following compound is administered

20. The method according to claim 3, which is for the sensitisation of cancer cells to an anticancer agent.

21. The method according to claim 3, which is for the sensitisation of cancer cells to ionising radiation.

22. The method according to claim 3, which is for the sensitisation of cancer cells to a combination of an anticancer agent and ionising radiation.

23. The method according to claim 3, wherein a solvate of one of the following compounds is administered:

30. The method according to claim 3, wherein a pharmaceutically acceptable salt of the following compound is administered

31. The method according to claim 3, wherein a pharmaceutically acceptable salt of the following compound is administered

32. The method according to claim 3, wherein a pharmaceutically acceptable salt of the following compound is administered

33. The method according to claim 3, wherein a pharmaceutically acceptable salt of the following compound is administered

34. The method according to claim 3, wherein a pharmaceutically acceptable salt of the following compound is administered

35. The method according to claim 3, wherein a pharmaceutically acceptable salt of the following compound is administered

36. The method according to claim 3, wherein a pharmaceutically acceptable salt of the following compound is administered

37. The method according to claim 3, wherein a pharmaceutically acceptable salt of the following compound is administered

38. The method according to claim 3, wherein a pharmaceutically acceptable salt of the following compound is administered

39. The method according to claim 3, wherein a pharmaceutically acceptable salt of the following compound is administered

40. The method according to claim 3, wherein a pharmaceutically acceptable salt of the following compound is administered

41. The method according to claim 3, wherein a pharmaceutically acceptable salt of the following compound is administered

42. The method according to claim 3, wherein a pharmaceutically acceptable salt of the following compound is administered

43. The method according to claim 3, wherein a pharmaceutically acceptable salt of the following compound is administered