IL-8 receptor antagonists

• US 7,893,089 B2
• Filed: 04/20/2007
• Issued: 02/22/2011
• Est. Priority Date: 04/21/2006
• Status: Expired due to Fees

• Current Assignee: GlaxoSmithKline LLC (GSK plc)
• Original Assignee: GlaxoSmithKline LLC (GSK plc)
• Inventors: Busch-Petersen, Jakob
• Primary Examiner(s): CHANG, CELIA C
• Application Number:
  US11/738,148
• Publication Number:
  US 20070249672A1
• Time in Patent Office: 1,404 Days
• Field of Search: 514/317, 514/318, 546/216, 546/194
• US Class Current: 514/317
• 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 13/12 of the kidneys
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/04 Antipruritics
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 19/10 for osteoporosis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• 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 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 33/06 Antimalarials
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 37/08 : Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 39/02 : Antidotes
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/02 : Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• 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 205/04 : having no double bonds between ring members or between ring members and non-ring members
• CPC Class Codes: C07D 207/08 : with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
• CPC Class Codes: C07D 207/12 : Oxygen or sulfur atoms
• CPC Class Codes: C07D 209/02 : condensed with one carbocyclic ring
• CPC Class Codes: C07D 211/54 : Sulfur atoms
• CPC Class Codes: C07D 401/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 405/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 451/04 : with hetero atoms directly attached in position 3 of the 8-azabicyclo [3.2.1] octane or in position 7 of the 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring system

Abstract

This invention relates to novel compounds and compositions thereof, useful in the treatment of disease states mediated by the chemokine, Interleukin-8 (IL-8).

Claims

1. A compound selected from the group consisting of:

N-{4-chloro-2-hydroxy-3-[(3S)-3-piperidinylsulfonyl]phenyl}-N′

-(3-fluoro-2-methylphenyl)urea;

N-[4-chloro-2-hydroxy-3-(3-piperidinylsulfonyl)-phenyl]-N′

-(3-fluoro-2-methylphenyl)urea;

N-{4-chloro-2-hydroxy-3-[(3S)-3-piperidinylsulfonyl]phenyl}-N′

-(2-chloro-3-pyridinyl)urea; and

N-(2-chloro-3-fluorophenyl)-N′

-{4-chloro-2-hydroxy-3-[(3S)-3-piperidinyl-sulfonyl]phenyl}urea;

or a pharmaceutically acceptable salt thereof.

2. A compound according to claim 1 wherein the pharmaceutically acceptable salt is a hydrochloride salt.

3. A pharmaceutical composition comprising a compound according to claim 1 and a pharmaceutically acceptable carrier or diluent.

4. A method of treating asthma, chronic obstructive pulmonary disease or adult respiratory distress syndrome in a mammal in need thereof which method comprises administering to said mammal an effective amount of a compound according to claim 1.

5. The method according to claim 4 wherein the mammal is a human afflicted with chronic obstructive pulmonary disease.

6. The method according to claim 4 wherein the mammal is a human.

15. The compound according to claim 1 wherein the pharmaceutically acceptable salt is selected from the group consisting of hydrochloride, hydrobromide, sulfate, phosphate, methane sulfonate, ethane sulfonate, acetate, malate, tartrate, citrate, lactate, oxalate, succinate, fumarate, maleate, benzoate, salicylate, phenylacetate, and mandelate.

19. A pharmaceutical composition comprising a compound according to claim 1, or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier or diluent.

22. A method of treating psoriasis, atopic dermatitis, osteoarthritis, rheumatoid arthritis, inflammatory bowel disease, Crohn'"'"'s disease, or ulcerative colitis in a human in need thereof, comprising administering to said human an effective amount of a compound according to claim 1.

7. The compound which is N-{4-chloro-2-hydroxy-3-[(3S)-3-piperidinylsulfonyl]phenyl}-N′

-(3-fluoro-2-methylphenyl)urea, or a pharmaceutically acceptable salt thereof.

16. The compound according to claim 7 wherein the pharmaceutically acceptable salt is selected from the group consisting of hydrochloride, hydrobromide, sulfate, phosphate, methane sulfonate, ethane sulfonate, acetate, malate, tartrate, citrate, lactate, oxalate, succinate, fumarate, maleate, benzoate, salicylate, phenylacetate, and mandelate.

20. A method of treating asthma, chronic obstructive pulmonary disease or adult respiratory distress syndrome in a human in need thereof comprising administering to said human an effective amount of a compound according to claim 7.

8. A pharmaceutical composition comprising N-{4-chloro-2-hydroxy-3-[(3S)-3-piperidinylsulfonyl]phenyl}-N′

-(3-fluoro-2-methylphenyl)urea, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or diluent.

9. The compound which is N-{4-chloro-2-hydroxy-3-[(3S)-3-piperidinylsulfonyl]phenyl}-N′

-(3-fluoro-2-methylphenyl)urea.

21. A method of treating asthma, chronic obstructive pulmonary disease or adult respiratory distress syndrome in a human in need thereof comprising administering to said human an effective amount of a compound according to claim 9.

10. A pharmaceutical composition comprising N-{4-chloro-2-hydroxy-3-[(3S)-3-piperidinylsulfonyl]phenyl}-N′

-(3-fluoro-2-methylphenyl)urea and a pharmaceutically acceptable carrier or diluent.

11. The compound which is N-(2-chloro-3-fluorophenyl)-N′

-{4-chloro-2-hydroxy-3-[(3S)-3-piperidinylsulfonyl]phenyl}urea, or a pharmaceutically acceptable salt thereof.

18. The compound according to claim 11 wherein the pharmaceutically acceptable salt is selected from the group consisting of hydrochloride, hydrobromide, sulfate, phosphate, methane sulfonate, ethane sulfonate, acetate, malate, tartrate, citrate, lactate, oxalate, succinate, fumarate, maleate, benzoate, salicylate, phenylacetate, and mandelate.

12. A pharmaceutical composition comprising N-(2-chloro-3-fluorophenyl)-N′

-{4-chloro-2-hydroxy-3-[(3S)-3-piperidinylsulfonyl]phenyl}urea, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or diluent.

13. The compound which is N-(2-chloro-3-fluorophenyl)-N′

-{4-chloro-2-hydroxy-3-[(3S)-3-piperidinylsulfonyl]phenyl}urea.

14. A pharmaceutical composition comprising N-(2-chloro-3-fluorophenyl)-N′

-{4-chloro-2-hydroxy-3-[(3S)-3-piperidinylsulfonyl]phenyl}urea and a pharmaceutically acceptable carrier or diluent.

17. The compound which is N-[4-chloro-2-hydroxy-3-(3-piperidinylsulfonyl)-phenyl]-N′

-(3-fluoro-2-methylphenyl)urea, or a pharmaceutically acceptable salt thereof.

24. The compound according to claim 17 wherein the pharmaceutically acceptable salt is selected from the group consisting of hydrochloride, hydrobromide, sulfate, phosphate, methane sulfonate, ethane sulfonate, acetate, malate, tartrate, citrate, lactate, oxalate, succinate, fumarate, maleate, benzoate, salicylate, phenylacetate, and mandelate.

28. A method of treating a disease selected from the group consisting of asthma, chronic obstructive pulmonary disease, adult respiratory distress syndrome, psoriasis, atopic dermatitis, osteoarthritis, rheumatoid arthritis, inflammatory bowel disease, Crohn'"'"'s disease, and ulcerative colitis in a human in need thereof, comprising administering to said human an effective amount of a compound according to claim 17.

29. The method according to claim 28 wherein the disease is chronic obstructive pulmonary disease.

23. A pharmaceutical composition comprising N-{4-chloro-2-hydroxy-3-[(3S)-3-piperidinylsulfonyl]phenyl}-N′

-(3-fluoro-2-methylphenyl)urea, or a pharmaceutically acceptable salt thereof, or N-[4-chloro-2-hydroxy-3-(3-piperidinylsulfonyl)-phenyl]-N′

-(3-fluoro-2-methylphenyl)urea, or a pharmaceutically acceptable salt thereof, in admixture with a pharmaceutically acceptable carrier or diluent for administration by intravenous, intramuscular, subcutaneous, intravaginal, intraperitoneal, oral inhalation, or intranasal means.

25. The compound which is N-[4-chloro-2-hydroxy-3-(3-piperidinylsulfonyl)-phenyl]-N′

-(3-fluoro-2-methylphenyl)urea.

30. A method of treating a disease selected from the group consisting of asthma, chronic obstructive pulmonary disease, adult respiratory distress syndrome, psoriasis, atopic dermatitis, osteoarthritis, rheumatoid arthritis, inflammatory bowel disease, Crohn'"'"'s disease, and ulcerative colitis in a human in need thereof, comprising administering to said human an effective amount of a compound according to claim 25.

31. The method according to claim 30 wherein the disease is chronic obstructive pulmonary disease.

26. A pharmaceutical composition comprising N-[4-chloro-2-hydroxy-3-(3-piperidinylsulfonyl)-phenyl]-N′

-(3-fluoro-2-methylphenyl)urea, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or diluent.

27. A pharmaceutical composition comprising N-[4-chloro-2-hydroxy-3-(3-piperidinylsulfonyl)-phenyl]-N′

-(3-fluoro-2-methylphenyl)urea, and a pharmaceutically acceptable carrier or diluent.