Quinolinone derivatives and uses thereof

• US 20050261308A1
• Filed: 07/27/2005
• Published: 11/24/2005
• Est. Priority Date: 03/11/2003
• Status: Active Grant

• Current Assignee: Roche Palo Alto LLC (Roche Holding AG)
• Original Assignee: Roche Palo Alto LLC (Roche Holding AG)
• Inventors: Repke, David, Stabler, Russell, Harris, Ralph
• Granted Patent: US 7,476,675 B2
• Time in Patent Office: Days
• US Class Current: 514/253.70
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• 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 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/14 for treating abnormal movements, e.g. chorea, dyskinesia
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/24 Antidepressants
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 215/227 only one oxygen atom which is attached in position 2
• CPC Class Codes: C07D 223/16 Benzazepines; Hydrogenated benzazepines
• CPC Class Codes: C07D 265/36 condensed with one six-membered ring
• CPC Class Codes: C07D 401/06 linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 401/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 405/06 linked by a carbon chain containing only aliphatic carbon atoms

Abstract

The invention provides compounds of the formula:
and pharmaceutically acceptable salts or prodrugs thereof, wherein m, p, q, r, A, E, X, Y, R¹, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹ and are as defined herein. The invention also provides methods for preparing, compositions comprising, and methods for using compounds of formula I.

Claims

1-43. -43. (canceled)

44. A compound of the formula:

45. The compound of claim 44, wherein E is N.

46. The compound of claim 45, wherein n is 1.

47. The compound of claim 46, wherein R², R³, R^a and R^b are hydrogen.

48. The compound of claim 47, wherein q is 2 and r is 2.

49. The compound of claim 48, wherein p is 1.

50. The compound of claim 49, wherein m is 0.

51. The compound of claim 49, wherein m is 1 and R¹ is halo or alkoxy.

52. The compound of claim 49, wherein A is indolylene or pyrimidinylene.

53. The compound of claim 49, wherein R¹⁰ is hydrogen or alkyl.

54. The compound of claim 49, wherein R¹⁰ is arylalkyl, or aryloxyalkyl.

55. The compound of claim 54, wherein R¹⁰ is 2-(4-fluorophenyl)-ethyl or 2-(4-methoxyphenyl)-ethyl.

56. The compound of claim 45, wherein n is 2.

58. The compound of claim 44, wherein said compound is selected from the group consisting of:

1-(2-Chloro-6-piperazin-1-yl-pyrimidin-4-ylmethyl)-3,4-dihydro-1H-quinolin-2-one; and

1-(5-Piperazin-1-yl-1H-indol-3-ylmethyl)-3,4-dihydro-1H-quinolin-2-one.

59. A pharmaceutical composition comprising an efficacious amount of the compound of claim 44 in admixture with a pharmaceutically acceptable carrier.

60. A method for treating a 5-HT6 antagonist-mediated disease state in a subject, said disease state selected from the group consisting of Parkinson'"'"'s disease, Huntington'"'"'s disease, manic depression, psychoses, Alzheimer'"'"'s disease and memory disorders, said method comprising administering to said subject a therapeutically effective amount of a compound of claim 44.