7,8-dihydropyrido[2,3-d]pyrimidin-4-yl substituted compounds as inhibitors of p38 kinase

• US 8,354,416 B2
• Filed: 06/04/2008
• Issued: 01/15/2013
• Est. Priority Date: 03/25/2005
• Status: Expired due to Fees

• Current Assignee: Glaxo Group Limited (GSK plc)
• Original Assignee: Glaxo Group Limited (GSK plc)
• Inventors: Callahan, James F., Boehm, Jeffrey C., Cooper, Anthony William James, Livia, Stefano, Bamborough, Paul, Nevins, Neysa, Wan, Zehong, Norton, Beth A., Lin, Xichen
• Primary Examiner(s): Wilson, James O
• Assistant Examiner(s): Jaisle, Cecilia M
• Application Number:
  US12/132,793
• Publication Number:
  US 20090156597A1
• Time in Patent Office: 1,686 Days
• Field of Search: 544/279, 514/258.1, 514/264.11
• US Class Current: 514/264.11
• 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 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/02 Nasal agents, e.g. decongestants
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 17/16 Emollients or protectives, e.g. against radiation
• 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 19/06 Antigout agents, e.g. antihyperuricemic or uricosuric agents
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: A61P 19/10 for osteoporosis
• 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 25/28 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 27/00 Drugs for disorders of the senses
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/16 Otologicals
• 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 3/00 : Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/10 : for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/00 : Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/04 : Antibacterial agents
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 35/04 : specific for metastasis
• 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 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 9/04 : Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
• 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 487/04 : Ortho-condensed systems

Abstract

Novel substituted 2,4,8-trisubstituted 8H-pyrido[2,3-d]pyrimidin-7-one containing compounds and compositions, and their use in therapy as CSBP/RK/p38 kinase inhibitors.

Claims

1. The compound which is 3-[2-{[3-(diethylamino)propyl]amino}-8-(2,6-difluorophenyl)-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-4-yl]-5-fluoro-4-methyl-N-(1-methylethyl)benzamide, or a pharmaceutically acceptable salt thereof.

2. A pharmaceutical composition comprising a compound or a pharmaceutically acceptable salt thereof according to claim 1, in admixture with one or more pharmaceutically acceptable carriers, diluents or excipients.

3. The pharmaceutical composition according to claim 2 adapted for administration by intravenous, intramuscular, subcutaneous, intranasal, oral inhalation, intrarectal, intravaginal or intraperitoneal means.

4. The composition according to claim 3 adapted for intranasal or oral inhalation.

25. The composition according to claim 2 adapted for topical administration.

5. The compound which is 3-[2-{[3-(diethylamino)propyl]amino}-8-(2,6-difluorophenyl)-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-4-yl]-5-fluoro-4-methyl-N-(1-methylethyl)benzamide.

6. A pharmaceutical composition comprising a compound according to claim 5 in admixture with one or more pharmaceutically acceptable carriers, diluents or excipients.

7. The pharmaceutical composition according to claim 6 adapted for administration by intravenous, intramuscular, subcutaneous, intranasal, oral inhalation, intrarectal, intravaginal or intraperitoneal means.

8. The composition according to claim 7 adapted for intranasal or oral inhalation.

26. The composition according to claim 6 adapted for topical administration.

9. The compound which is N-cyclopropyl-3-[2-{[3-(diethylamino)propyl]amino}-8-(2,6-difluorophenyl)-7-oxo-7,8dihydropyrido[2,3-d]pyrimidin-4-yl]-5-fluoro-4-methylbenzamide, or a pharmaceutically acceptable salt thereof.

10. A pharmaceutical composition comprising a compound, or pharmaceutically acceptable salt thereof, according to claim 9 in admixture with one or more pharmaceutically acceptable carriers, diluents or excipients.

11. The pharmaceutical composition according to claim 10 adapted for administration by intravenous, intramuscular, subcutaneous, intranasal, oral inhalation, intrarectal, intravaginal or intraperitoneal means.

12. The composition according to claim 11 adapted for intranasal or oral inhalation.

27. The composition according to claim 10 adapted for topical administration.

13. The compound which is N-cyclopropyl-3-[2-{[3-(diethylamino)propyl]amino}-8-(2,6-difluorophenyl)-7-oxo-7,8dihydropyrido[2,3-d]pyrimidin-4-yl]-5-fluoro-4-methylbenzamide.

14. A pharmaceutical composition comprising a compound according to claim 13 in admixture with one or more pharmaceutically acceptable carriers, diluents or excipients.

15. The pharmaceutical composition according to claim 14 adapted for administration by intravenous, intramuscular, subcutaneous, intranasal, oral inhalation, intrarectal, intravaginal or intraperitoneal means.

16. The composition according to claim 15 adapted for intranasal or oral inhalation.

28. The composition according to claim 14 adapted for topical administration.

17. The compound which is 3-{8-(2,6-difluorophenyl)-2-[(1H-imidazol-2-ylmethyl)amino]-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-4-yl}-4-methyl-N-1,3-thiazol-2-ylbenzamide, or a pharmaceutically acceptable salt thereof.

18. A pharmaceutical composition comprising a compound, or pharmaceutically acceptable salt thereof, according to claim 17 in admixture with one or more pharmaceutically acceptable carriers, diluents or excipients.

19. The pharmaceutical composition according to claim 17 adapted for administration by intravenous, intramuscular, subcutaneous, intranasal, oral inhalation, intrarectal, intravaginal or intraperitoneal means.

20. The composition according to claim 19 adapted for intranasal or oral inhalation.

29. The composition according to claim 18 adapted for topical administration.

21. The compound which is 3-{8-(2,6-difluorophenyl)-2-[(1H-imidazol-2-ylmethyl)amino]-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-4-yl}-4-methyl-N-1,3-thiazol-2-ylbenzamide.

22. A pharmaceutical composition comprising a compound, according to claim 21 in admixture with one or more pharmaceutically acceptable carriers, diluents or excipients.

23. The pharmaceutical composition according to claim 22 adapted for administration by intravenous, intramuscular, subcutaneous, intranasal, oral inhalation, intrarectal, intravaginal or intraperitoneal means.

24. The composition according to claim 23 adapted for intranasal or oral inhalation.

30. The composition according to claim 22 adapted for topical administration.