IL-8 receptor antagonists

• US 7,709,485 B2
• Filed: 10/09/2007
• Issued: 05/04/2010
• Est. Priority Date: 10/29/2002
• Status: Expired due to Term

• Current Assignee: GlaxoSmithKline LLC (GSK plc)
• Original Assignee: GlaxoSmithKline LLC (GSK plc)
• Inventors: Widdowson, Katherine L., Palovich, Michael R, Busch-Petersen, Jakob
• Primary Examiner(s): BERNHARDT, EMILY A
• Application Number:
  US11/869,055
• Publication Number:
  US 20090093492A1
• Time in Patent Office: 938 Days
• Field of Search: None
• US Class Current: 514/252.12
• 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 13/12 of the kidneys
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 19/10 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 31/16 for influenza or rhinoviruses
• CPC Class Codes: A61P 33/06 Antimalarials
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• 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 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• 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 295/26 : Sulfur atoms
• CPC Class Codes: Y02A 50/30 : Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

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

Claims

1. The compound N-[4-chloro-2-hydroxy-3-(1-piperazinylsulfonyl) phenyl]-N′

-(2-chloro-3-fluorophenyl) urea, or a pharmaceutically acceptable salt thereof.

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

3. A method of treating a ELR chemokine mediated disease, wherein the chemokine binds to an IL-8 β

(CXCR2) receptor in a human comprising administering to said human in need thereof an effective amount of a compound according to claim 1, and wherein the disease is selected from the group consisting of asthma, chronic obstructive pulmonary disease and adult respiratory distress syndrome.

4. The method according to claim 3 wherein the disease is chronic obstructive pulmonary disease.

5. A method of treating a ELR chemokine mediated disease, wherein the chemokine binds to an IL-8 β

(CXCR2) receptor in a human, comprising administering to said human in need thereof an effective amount of a compound according to claim 1, and wherein the disease is selected from the group consisting of inflammatory bowel disease, Crohn'"'"'s disease, or ulcerative colitis.

6. The method according to claim 5 wherein the disease is ulcerative colitis.

7. The method according to claim 5 wherein the disease is inflammatory bowel disease.

8. A method of treating a ELR chemokine mediated disease, wherein the chemokine binds to an IL-8 β

(CXCR2) receptor in a human comprising administering to said human in need thereof an effective amount of a compound according to claim 1, and wherein the disease is selected from the group consisting of psoriasis and atopic dermatitis.

9. The method according to claim 5 wherein the disease is psoriasis.

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

11. The compound N-[4-chloro-2-hydroxy-3-(1-piperazinylsulfonyl)phenyl]-N′

-(2-chloro-3-fluorophenyl) urea.

12. A pharmaceutical composition comprising a compound according to claim 11 and a pharmaceutically acceptable carrier or diluent.