1H-imidazopyridine derivatives

• US 6,518,265 B1
• Filed: 05/02/2001
• Issued: 02/11/2003
• Est. Priority Date: 08/12/1998
• Status: Expired due to Fees

• Current Assignee: Hokuriku Seiyaku Co., Ltd. (Abbott Laboratories)
• Original Assignee: Hokuriku Seiyaku Co., Ltd. (Abbott Laboratories)
• Inventors: Kato, Hideo, Sakaguchi, Jun, Kato, Ken-ichi, Aoyama, Makoto, Izumi, Tomoyuki
• Primary Examiner(s): Seaman, D. Margaret
• Assistant Examiner(s): ROBINSON, BINTA M
• Application Number:
  US09/744,959
• Time in Patent Office: 650 Days
• Field of Search: 546/82, 514/293, 514/228.5, 514/238.8, 514/252.16, 544/60, 544/115, 544/361
• US Class Current: 514/228.5
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• 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 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/02 Immunomodulators
• 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: C07D 471/04 Ortho-condensed systems

Abstract

1H-Imidazopyridine derivatives represented by the following general formula or salts thereof:

wherein R¹ represents hydrogen atom, hydroxyl group, an alkyl group, a cycloalkyl group, styryl group, or an aryl group; R² represents hydrogen atom, an alkyl group, a halogen atom, hydroxyl group, amino group, a cyclic amino group, or phenoxy group; ring A represents a homocyclic or heterocyclic ring which may be substituted; R³ represents a saturated nitrogen-containing heterocyclic group; and m represents an integer of from 0 to 3. The derivatives have excellent inhibitory actions against production of TNF or IL-1 and are extremely useful as preventive or therapeutic agents for diseases in which a cytokine is mediated.

Claims

1. A compound represented by the following formula or salt thereof:

wherein R¹ represents hydrogen atom, hydroxyl group, an alkyl group which may have one or more substituents, a cycloalkyl group which may be substituted, a styryl group which may be substituted, or an aryl group which may have one or more substituents;

R² represents hydrogen atom, an alkyl group, a halogen atom, hydroxyl group, an amino group which may have one or two substituents, a cyclic amino group which may be substituted, or a phenoxy group which may be substituted;

ring A represents a benzene, cyclohexene, cyclopentene, or thiophene ring which may be substituted with one or more alkyl groups, alkoxy groups, or halogen atoms;

R³ represents a saturated nitrogen-containing heterocyclic group which may be substituted; and

m represents an integer of from 0 to 3;

provided that when R³ represents unsubstituted piperidino group, at least one of R¹ and R² is not hydrogen atom.

2. The compound or salt thereof according to claim 1, wherein the ring A is benzene ring or thiophene ring.

3. The compound or salt thereof according to claim 1, comprising 4-chloro-2-phenyl-1-[2-(4-piperidyl)ethyl]-1H-imidazo[4,5-c]quinoline or a salt thereof.

4. The compound or salt thereof according to claim 1, comprising 4-amino-1-[2-(4-piperidyl)ethyl]-1H-imidazo[4,5-c]quinoline or a salt thereof.

5. The compound or salt thereof according to claim 1, comprising the formula:

or a salt thereof.

6. The compound or salt thereof according to claim 1, comprising the formula:

or a salt thereof.

7. The compound or salt thereof according to claim 1, comprising the formula:

or a salt thereof.

8. The compound or salt thereof according to claim 1, comprising the formula:

or a salt thereof.

9. A pharmaceutical composition comprising a pharmaceutically effective amount of the compound or salt thereof according to claim 1.

10. A method of inhibiting cytokine production comprising administering a compound or salt thereof according to claim 1 to a mammal.

11. The method of claim 10, wherein the mammal is a human.

12. A method of inhibiting TNF or IL-1 production comprising administering a compound or salt thereof according to claim 1 to a mammal.

13. The method of claim 12, wherein the mammal is a human.

14. A method of therapeutic treatment of a disease by inhibiting cytokine production, comprising administering a compound or salt thereof according to claim 1 to a mammal.

15. The method of claim 14, wherein the mammal is a human.

16. A method of preventive treatment of a disease by inhibiting cytokine production, comprising administering a compound or salt thereof according to claim 1 to a mammal.

17. The method of claim 16, wherein the mammal is a human.

18. A compound represented by the following formula or salt thereof:

wherein R¹ represents hydrogen atom, hydroxyl group, an alkyl group which may have one or more substituents, a cycloalkyl group which may be substituted, a styryl group which may be substituted, or an aryl group which may have one or more substituents;

R² represents hydrogen atom, an alkyl group, a halogen atom, hydroxyl group, an amino group which may have one or two substituents, a cyclic amino group which may be substituted, or a phenoxy group which may be substituted;

ring A represents a benzene, cyclohexene, cyclopentene, or thiophene ring which may be substituted with one or more alkyl groups, alkoxy groups, or halogen atoms;

m represents an integer of from 0 to 3;

R⁴ represents hydrogen atom, an alkyl group, benzyl group, triphenylmethyl group, an alkanoyl group which may be substituted, an alkoxycarbonyl group, benzyloxycarbonyl group, a thiocarbamoyl group which may be substituted, an alkanesulfonyl group, a benzenesulfonyl group which may be substituted, or amidino group;

Y represents methylene group, oxygen atom, sulfur atom, nitrogen atom, a group represented by NH, or a single bond; and

n represents an integer of from 0 to 2;

provided that when Y represents methylene group and n represents 1 and R⁴ represents hydrogen atom at least one of R¹ and R² is not hydrogen atom.

19. The compound or salt thereof according to claim 18, wherein the ring A is benzene ring or thiophene ring.

20. A pharmaceutical composition comprising a pharmaceutically effective amount of the compound or salt thereof according to claim 18.

21. A method of inhibiting cytokine production comprising administering a compound or salt thereof according to claim 18 to a mammal.

22. The method of claim 21, wherein the mammal is a human.

23. A method of inhibiting TNF or IL-1 production comprising administering a compound or salt thereof according to claim 18 to a mammal.

24. The method of claim 23, wherein the mammal is a human.

25. A method of therapeutic treatment of a disease by inhibiting cytokine production, comprising administering a compound or salt thereof according to claim 18 to a mammal.

26. The method of claim 25, wherein the mammal is a human.

27. A method of preventive treatment of a disease by inhibiting cytokine production, comprising administering a compound or salt thereof according to claim 18 to a mammal.

28. The method of claim 27, wherein the mammal is a human.