Quinoline derivatives and their use as 5-HT 6 ligands

• US 8,236,947 B2
• Filed: 06/03/2011
• Issued: 08/07/2012
• Est. Priority Date: 03/27/2002
• Status: Expired due to Term

• Current Assignee: Axovant Sciences Ltd.
• Original Assignee: Glaxo Group Limited (GSK plc)
• Inventors: Ahmed, Mahmood, Johnson, Christopher Norbert, Jones, Martin C, MacDonald, Gregor James, Moss, Stephen Frederick, Thompson, Mervyn, Wade, Charles Edward, Witty, David R
• Primary Examiner(s): BERNHARDT, EMILY A
• Application Number:
  US13/152,356
• Publication Number:
  US 20110237792A1
• Time in Patent Office: 431 Days
• Field of Search: None
• US Class Current: 540/575
• 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 1/14 Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/06 Antimigraine agents
• CPC Class Codes: A61P 25/08 Antiepileptics; Anticonvulsants
• 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 25/20 Hypnotics; Sedatives
• CPC Class Codes: A61P 25/22 Anxiolytics
• 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 25/30 for treating abuse or dependence
• CPC Class Codes: A61P 25/32 Alcohol-abuse
• CPC Class Codes: A61P 25/34 Tobacco-abuse
• CPC Class Codes: A61P 25/36 Opioid-abuse
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 215/00 Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
• CPC Class Codes: C07D 487/04 : Ortho-condensed systems
• CPC Class Codes: C07D 487/08 : Bridged systems

Abstract

Disclosed are quinoline compounds having affinity for the 5-HT₆ receptor and having the formula:

where R¹, R², R³, R⁴, R⁵, n, m, p and A are defined herein, and salts thereof, compositions containing these compounds and salts and processes for making and using the same.

Claims

1. A compound of formula (I):

2. The compound or salt according to claim 1, wherein R¹ represents hydrogen, methyl, ethyl, isopropyl, isobutyl or 2,2-dimethylpropyl.

3. The compound or salt according to claim 1, wherein R¹ represents hydrogen or methyl.

4. The compound or salt according to claim 1, wherein R² represents hydrogen, methyl.

5. The compound or salt according to claim 1, wherein m is 1 and R² represents 3-methyl or 2-methyl, or m is 2 and R² represents 3,3-dimethyl or 2,5-dimethyl.

6. The compound or salt according to claim 1, wherein R² is linked to R¹ to form a (CH₂)₃ group.

7. The compound or salt according to claim 1, wherein R² represents hydrogen or methyl.

8. The compound or salt according to claim 1, wherein R³ represents hydrogen, methyl or halogen.

9. The compound or salt according to claim 1, wherein R³ represents hydrogen.

10. The compound or salt according to claim 1, wherein R⁴ and R⁵ independently represent hydrogen or methyl.

11. The compound or salt according to claim 1, wherein n represents 1.

12. The compound or salt according to claim 1, wherein m and p independently represent 1 or 2.

13. The compound or salt according to claim 1, wherein m and p both represent 1.

14. The compound or salt according to claim 1, wherein m represents 2 and both R² groups are linked to form a CH₂ group linking C-2 and C-5 of the piperazine ring.

15. The compound or salt according to claim 1, wherein A represents an optionally substituted phenyl.

16. The compound or salt according to claim 15, wherein A represents a phenyl optionally substituted with halogen, cyano, trifluoromethyl or trifluoromethoxy.

17. The compound or salt according to claim 15, wherein A is unsubstituted phenyl.

18. The compound or salt according to claim 1, wherein A represents a phenyl substituted by halogen, C_1-6 alkyl, C_1-6 alkoxy, trifluoromethyl or trifluoromethoxy.