Benzenesulfonyl-asymmetric ureas and medical uses thereof

• US 10,501,479 B2
• Filed: 03/21/2017
• Issued: 12/10/2019
• Est. Priority Date: 03/22/2016
• Status: Active Grant

• Current Assignee: Helsinn Healthcare SA
• Original Assignee: Helsinn Healthcare SA
• Inventors: Giuliano, Claudio, Daina, Antoine, Pietra, Claudio
• Primary Examiner(s): Bernhardt, Emily A
• Assistant Examiner(s): Daniel, Laura M
• Application Number:
  US15/464,430
• Publication Number:
  US 20170275301A1
• Time in Patent Office: 994 Days
• Field of Search: None
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 25/30 for treating abuse or dependence
• CPC Class Codes: A61P 25/32 Alcohol-abuse
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07C 2601/02 with a three-membered ring
• CPC Class Codes: C07C 311/47 Y being a hetero atom
• CPC Class Codes: C07C 317/14 having sulfone or sulfoxide groups bound to carbon atoms of six-membered aromatic rings
• CPC Class Codes: C07C 317/26 having sulfone or sulfoxide groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton
• CPC Class Codes: C07C 317/42 Y being a hetero atom
• CPC Class Codes: C07C 317/44 having sulfone or sulfoxide groups and carboxyl groups bound to the same carbon skeleton
• CPC Class Codes: C07D 209/04 Indoles; Hydrogenated indoles
• CPC Class Codes: C07D 209/08 with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
• CPC Class Codes: C07D 209/44 Iso-indoles; Hydrogenated iso-indoles
• CPC Class Codes: C07D 213/34 to which a second hetero atom is attached
• CPC Class Codes: C07D 213/76 to which a second hetero atom is attached nitro radicals C07D213/61
• CPC Class Codes: C07D 215/06 having only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, attached to the ring nitrogen atom
• CPC Class Codes: C07D 215/08 with acylated ring nitrogen atom
• CPC Class Codes: C07D 215/10 Quaternary compounds
• CPC Class Codes: C07D 215/58 : with hetero atoms directly attached to the ring nitrogen atom
• CPC Class Codes: C07D 217/04 : with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom
• CPC Class Codes: C07D 217/10 : Quaternary compounds
• CPC Class Codes: C07D 223/16 : Benzazepines; Hydrogenated benzazepines
• CPC Class Codes: C07D 231/56 : Benzopyrazoles; Hydrogenated benzopyrazoles
• CPC Class Codes: C07D 233/64 : with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
• CPC Class Codes: C07D 235/14 : Radicals substituted by nitrogen atoms by nitro radicals C07D235/10
• CPC Class Codes: C07D 237/20 : Nitrogen atoms nitro radicals C07D237/12
• CPC Class Codes: C07D 239/26 : with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
• CPC Class Codes: C07D 239/48 : Two nitrogen atoms
• CPC Class Codes: C07D 241/04 : having no double bonds between ring members or between ring members and non-ring members
• CPC Class Codes: C07D 241/12 : with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
• CPC Class Codes: C07D 295/088 : to an acyclic saturated chain
• CPC Class Codes: C07D 307/87 : Benzo [c] furans; Hydrogenated benzo [c] furans
• CPC Class Codes: C07D 311/76 : Benzo[c]pyrans
• CPC Class Codes: C07D 317/34 : Oxygen atoms
• CPC Class Codes: C07D 401/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 403/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 405/04 : directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 405/06 : linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 405/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 409/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 413/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 417/10 : linked by a carbon chain containing aromatic rings
• CPC Class Codes: C07D 417/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 471/04 : Ortho-condensed systems
• CPC Class Codes: C07D 471/08 : Bridged systems
• CPC Class Codes: C07D 487/04 : Ortho-condensed systems
• CPC Class Codes: C07D 495/04 : Ortho-condensed systems
• CPC Class Codes: C07D 513/04 : Ortho-condensed systems

Abstract

Benzenesulfonyl-asymmetric ureas are provided for the treatment of conditions modulated by the ghrelin receptor.

Claims

1. A compound of Formula IV:

2. The compound of claim 1, wherein X is CO.

3. The compound of claim 1, wherein X is a bond.

4. The compound of claim 1, wherein said X is C_1-3 alkyl.

5. The compound of claim 1, wherein X is CH(CH₃).

6. The compound of claim 1, wherein X is C(CH₃)₂.

7. The compound of claim 1, wherein X is CHCF₃.

8. The compound of claim 1, wherein X is CH(CH₂CH₃).

9. The compound of claim 1, wherein X is C_1-3 alkyl substituted with halo.

10. The compound of claim 1, wherein

11. The compound of claim 1, wherein

12. The compound of claim 1, wherein R¹ is OH.

13. The compound of claim 1, wherein R¹ is CH₃.

14. The compound of claim 1, wherein R² is CH₃.

15. The compound of claim 1, wherein R³ is F.

16. The compound of claim 1, wherein R³ is Cl.

17. The compound of claim 1, wherein R³ is methoxy.

18. The compound of claim 1, wherein R⁴ is CR⁹R¹⁰.

19. The compound of claim 1, wherein R⁴ is CH₂.

20. The compound of claim 1, wherein R⁴ is CHCH₃ .

21. The compound of claim 1, wherein R⁴ is C(CH₃)₂.

22. The compound of claim 1, wherein R⁴ is NCH_3.

23. The compound of claim 1, wherein R⁴ and R³ come together to form a 5-membered heterocyclic ring.

24. The compound of claim 1, wherein

25. The compound of claim 1, wherein

26. The compound of claim 1, wherein

27. The compound of claim 1, wherein

28. The compound of claim 1, wherein

29. The compound of claim 1, wherein

30. The compound of claim 1, wherein p is 1.

31. The compound of claim 1, wherein p is 2.

32. The compound of claim 1, wherein n is 0.

33. A compound or a pharmaceutically acceptable salt thereof selected from the group consisting of:

34. A compound selected from the group consisting of:

35. The compound of claim 34 having the structure:

36. The compound of claim 34 having the structure:

37. The compound of claim 34 having the structure:

38. The compound of claim 34 having the structure:

39. The compound of claim 34 having the structure:

40. The compound of claim 34 having the structure:

41. The compound of claim 34 having the structure:

42. The compound of claim 34 having the structure:

43. The compound of claim 34 having the structure:

44. The compound of claim 34 having the structure:

45. The compound of claim 34 having the structure:

46. The compound of claim 34 having the structure:

47. The compound of claim 34 having the structure:

48. The compound of claim 34 having the structure:

49. The compound of claim 34 having the structure:

50. The compound of claim 34 having the structure:

51. The compound of claim 34 having the structure: