Quinoline derivatives

• US 6,605,616 B1
• Filed: 07/21/2000
• Issued: 08/12/2003
• Est. Priority Date: 07/15/1998
• Status: Expired due to Term

• Current Assignee: Active Biotech AB
• Original Assignee: Active Biotech AB
• Inventors: Hedlund, Gunnar, Fex, Tomas, Björk, Anders, Jönsson, Stig
• Primary Examiner(s): Huang, Evelyn Mei
• Application Number:
  US09/621,486
• Time in Patent Office: 1,117 Days
• Field of Search: 546/90, 546/155, 544/128, 514/232.8, 514/291, 514/312
• US Class Current: 514/312
• 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 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: C07D 215/56 with oxygen atoms in position 4

Abstract

The invention is related to compounds of general formula (I)

wherein R is methyl, ethyl, n-propyl, iso-propyl, n-butyl or allyl; R′ is methyl, methoxy, fluoro, chloro, bromo, azido, trifluorometlhyl, or OCH_xF_y, wherein x=0−2, y=1−3 with the. proviso that x+y=3; R″ is hydrogen, fluoro or chloro; with the proviso that R″ is fluoro or chloro only when R′ is fluoro or chloro; R₄ is hydrogen or pharmaceutically acceptable inorganic or organic cations; R₅ is dimethylamino or nitro; R₆ is hydrogen; and when R′ is azido R₅ is also ethyl, n-propyl, iso-propyl, methoxy, ethoxy, chloro, bromo, trifluoromethyl, OCH_xF_y, wherein x=0−2, y=1−3 with the proviso that x+y=3, or R₅ and R₆ taken together are methylenedioxy; and any tautomer thereof. The invention also relates to pharmaceutical compositions containing a compound of the general formula (I) together with a pharmaceutically acceptable carrier. Included are also processes for the preparation of the compounds of formula (I), as well as methods for the treatment of mammals suffering from diseases resulting from autoimmunity and pathological inflammation by administering of a compound having the formula (I) to said mammal.

Claims

1. N-methyl-N-(4-methoxy-phenyl)-1,2-dihydro-4-hydroxy-5-dimethylamino-1-methyl-2-oxo-quinoline-3-carboxamide.

2. A pharmaceutical composition comprising as active ingredient a therapeutically effective amount of a compound having the formula (I) of claim 1 together with a pharmaceutical carrier.

3. A pharmaceutical composition according to claim 2 in unit dosage form sufficient to provide a daily dose of the active substance of 0.0005 mg/kg to about 10 mg/kg body weight.

4. A pharmaceutical composition according to claim 2 in unit dosage form sufficient to provide a daily dose of the active substance of 0.005 to 1 mg/kg body weight.

5. A method of treating a mammal suffering from pathologic inflammation or a disease result in from autoimmunity comprising

administering to said mammal an amount sufficient for said treatment of the compound of claim 1 or a pharmaceutically acceptable salt or tautomer thereof.

6. The method according to claim 5 wherein said mammal is one suffering from multiple sclerosis (MS).

7. The method according to claim 5 wherein said mammal is one suffering from insulin-dependent diabetes mellitus (IDDM).

8. The method according to claim 5 wherein said mammal is one suffering from systemic lupus erythematosus (SLE).

9. The method according to claim 5 wherein said mammal is one suffering from rheumatoid arthritis (RA).

10. The method according to claim 5 wherein said mammal is one suffering from inflammatory bowel disease (IBD).

11. The method according to claim 5 wherein said mammal is one suffering from psoriasis.

12. The method according to claim 5 wherein said mammal is one suffering from inflammatory respiratory disorder.

13. The method according to claim 5 wherein said mammal is one suffering from asthma.

14. The method according to claim 5 wherein said mammal is one suffering from atherosclerosis.

15. The method according to claim 5 wherein said mammal is one suffering from stroke.

16. The method according to claim 5 wherein said mammal is one suffering from Alzheimer'"'"'s disease.

17. The method according to claim 5, wherein said amount is 0.0005 mg/kg to about 10 mg/kg body weight.

18. The method according to claim 5, wherein said amount is 0.005 mg/kg to about 1 mg/kg body weight.