Urea derivatives and their use as vanilloid receptor antagonists in the treatment of pain

• US 7,514,562 B2
• Filed: 03/04/2004
• Issued: 04/07/2009
• Est. Priority Date: 03/07/2003
• Status: Expired due to Fees

• Current Assignee: Glaxo Group Limited (Glaxosmithkline Holdings Ltd.)
• Original Assignee: Glaxo Group Limited (Glaxosmithkline Holdings Ltd.)
• Inventors: Rami, Harshad Kantilal, Witty, David Richard, Fell, Stephen Christopher Martin, Thompson, Mervyn
• Primary Examiner(s): Desai; Rita J
• Assistant Examiner(s): Mabry; John
• Application Number:
  US10/548,132
• Publication Number:
  US 20060276447A1
• Time in Patent Office: 1,860 Days
• Field of Search: 546/276.4, 514/210.2
• US Class Current: 546/276.4
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/02 Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
• 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 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 11/08 Bronchodilators
• CPC Class Codes: A61P 13/02 of urine or of the urinary tract, e.g. urine acidifiers
• CPC Class Codes: A61P 13/10 of the bladder
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 17/04 Antipruritics
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• 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 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/06 Antimigraine agents
• 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 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 29/02 : without antiinflammatory effect
• CPC Class Codes: A61P 3/10 : for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/18 : for HIV
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07D 401/04 : directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 401/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 401/14 : containing three or more hetero rings
• CPC Class Codes: C07D 403/12 : linked by a chain containing hetero atoms as chain links

Abstract

Compounds of formula (I),

or a pharmaceutically acceptable salt or solvate thereof, wherein P, P′, W, R¹, R², n, p, q, r, s and t are as defined in the specification, processes for preparing such compounds, pharmaceutical compositions comprising such compounds and their use in therapy.

Claims

1. A compound represented by the following formula:

2. A compound according to claim 1 or a pharmaceutically acceptable salt thereof wherein P represents phenyl.

3. A compound according to claim 1 or a pharmaceutically acceptable salt thereof wherein p and q each independently represent 1 or 2.

4. A compound according to claim 3 or a pharmaceutically acceptable salt thereof wherein each R² independently represents —

CH₃ or —

CF₃; and

each R¹ independently —

F, —

Cl, —

Br, CH₃,or —

CF₃.

5. A compound according to claim 1 or a pharmaceutically acceptable salt thereof, which compound is selected from the group consisting of:

N-(2-Trifluoromethylphenyl)-N′

-[(1-(6-trifluoromethyl-2-pyridyl)azetidin-3-yl)]urea;

N-(2-Bromophenyl)-N′

-[(1-(6-methyl-4-trifluoromethyl-2-pyridyl)azetidin-3-yl)]urea;

N-(2-Chlorophenyl)-N′

-[(1-(6-methyl-4-trifluoromethyl-2-pyridyl)azetidin-3-yl)]urea; and

N-(2,3-Dichlorophenyl)-N′

-[(1-(6-methyl-4-trifluoromethyl-2-pyridyl)azetidin-3-yl)]urea.

6. A pharmaceutical composition comprising a compound according to claim 1 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier or excipient.

7. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein P represents 5-isoquinolinyl.

8. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein P represents 5-cinnolinyl.

9. The compound according to claim 6 or a pharmaceutically acceptable salt thereof, where R² represents CF₃.

10. A compound represented by the following formula:

11. The compound of claim 10 or a pharmaceutically acceptable salt thereof wherein each q is 0 or 1;

and

each R¹ and each R² are independently —

F, —

Cl, —

Br, —

CH₃, or —

CF₃.

12. The compound of claim 11 or a pharmaceutically acceptable salt thereof wherein each q is 1 and each R² is —

F.

13. The compound of claim 11 or a pharmaceutically acceptable salt thereof wherein each q is 0.

14. The compound of claim 10 which is N-(1-Methylisoquinolin-5-yl)-N′

-(1-diphenylmethylazetidin-3 -yl)-urea or a pharmaceutically acceptable salt thereof.