NITROGENATED HETEROCYCLIC COMPOUND AND PHARMACEUTICAL COMPOSITION COMPRISING THE SAME

• US 20090306396A1
• Filed: 10/03/2006
• Published: 12/10/2009
• Est. Priority Date: 10/07/2005
• Status: Active Grant

• Current Assignee: Kissei Pharmaceutical Company Limited
• Original Assignee: Kissei Pharmaceutical Company Limited
• Inventors: Hoshino, Chikara, Takeda, Masakazu, Toyoshima, Takahiro, Sasaki, Toshinobu
• Granted Patent: US 7,947,707 B2
• Time in Patent Office: Days
• US Class Current: 548/204
• CPC Class Codes: A61P 19/06 Antigout agents, e.g. antihyperuricemic or uricosuric agents
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• 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 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• 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 207/416 with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to other ring carbon atoms
• CPC Class Codes: C07D 209/42 Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
• CPC Class Codes: C07D 231/14 with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
• CPC Class Codes: C07D 403/10 linked by a carbon chain containing aromatic rings
• CPC Class Codes: C07D 405/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 405/14 containing three or more hetero rings
• CPC Class Codes: C07D 409/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 413/14 containing three or more hetero rings
• CPC Class Codes: C07D 417/10 linked by a carbon chain containing aromatic rings
• CPC Class Codes: C07D 417/14 containing three or more hetero rings
• CPC Class Codes: C07D 471/04 Ortho-condensed systems
• CPC Class Codes: C07D 491/056 with two or more oxygen atoms as ring hetero atoms in the oxygen-containing ring

Abstract

The present invention relates to novel compounds having a xanthine oxidase inhibitory effect and an uricosuric effect and pharmaceutical compositions comprising the same as an active ingredient. That is, the present invention relates nitrogen-containing heterocyclic compounds represented by the following general formula (I):

wherein Y¹ represents N or C(R⁴); Y² represents N or C(R⁵); R⁴ and R⁵ independently represent an alkyl group, a hydrogen atom etc.; one of R¹ and R² represents an optionally substituted aryl group, an alkoxy group or an optionally substituted heterocyclic group; the other of R¹ and R² represents a haloalkyl group, a cyano group, a halogen atom etc.; and R³ represents a 5-tetrazolyl group or a carboxy group, and pharmaceutically acceptable salts thereof, and pharmaceutical compositions comprising the same as an active ingredient.

Claims

1. A nitrogen-containing heterocyclic compound represented by the following general formula (I):

wherein Y¹ represents N or C(R⁴);

Y² represents N or C(R⁵);

R⁴ and R⁵ independently represents an alkyl group which may have a halogen atom, a hydrogen atom, a halogen atom, a cyano group or an alkoxy group;

one of R¹ and R² represents an haloalkyl group, a cyano group, a carbamoyl group or a halogen atom;

the other of R¹ and R² represents an aryl group which may have a substituent selected from the group consisting of an alkyl group, a haloalkyl group, an alkoxy group and a halogen atom in which some of the substituents may form a ring, an alkoxy group or a heterocyclic group selected from the group consisting of a thienyl, thiazolyl or pyrrolyl group which may be substituted by an alkyl group or a halogen atom; and

R³ represents a 5-tetrazolyl group or a carboxy group; and

with the proviso that when Y² represents CR⁵, y² may form a benzene or pyridine ring which may have a haloalkyl group, a halogen atom, a cyano group or an alkoxy group as a substituent together with R², and some of the neighboring substituents on the ring may form a ring, or a pharmaceutically acceptable salt thereof.

2. A nitrogen-containing heterocyclic compound as claimed in claim 1 represented by the following general formula (I-A) or (I-B):

wherein R^4a and R^5a independently represent a hydrogen atom or an alkyl group;

one of R^1a and R^2a represents a haloalkyl group, a cyano group or a halogen atom;

the other of R^1a and R^2a represents an aryl group which may have a substituent selected from the group consisting of an alkyl group, a haloalkyl group, an alkoxy group and a halogen atom in which some of the substituents may form a ring, an alkoxy group or a heterocyclic group selected from the group consisting of a thienyl, thiazolyl or pyrrolyl group which may be substituted by an alkyl group or a halogen atom; and

R³ represents a 5-tetrazolyl group or a carboxy group, or a pharmaceutically acceptable salt thereof.

3. A nitrogen-containing heterocyclic compound as claimed in claim 2, wherein R^1a represents a cyano group, or a pharmaceutically acceptable salt thereof.

4. A nitrogen-containing heterocyclic compound as claimed in claim 3, wherein R^2a represents an aryl group which may have a substituent selected from the group consisting of an alkyl group, a haloalkyl group, an alkoxy group and a halogen atom in which some of the substituents may form a ring;

an alkoxy group;

or a thienyl group which may be substituted by an alkyl group or a halogen atom, or a pharmaceutically acceptable salt thereof.

5. A nitrogen-containing heterocyclic compound as claimed in claim 2, wherein R³ represents a carboxy group, or a pharmaceutically acceptable salt thereof.

6. A nitrogen-containing heterocyclic compound as claimed in claim 1 represented by the following general formula (I-C):

wherein Y^1C represents N or C(R^4C);

Y³ represents N or C(R⁹);

R^4C and R⁹ independently represent an alkyl group, a haloalkyl group, a hydrogen atom, a halogen atom, a cyano group or an alkoxy group;

R^1C represents a cyano group or a carbamoyl group;

R⁶, R⁷ and R⁸ independently represent an alkyl group, a haloalkyl group, a hydrogen atom, a halogen atom, a cyano group or an alkoxy group;

or any of R⁶, R⁷ and R⁸ may form a ring together with the neighboring substituent; and

R³ represents a 5-tetrazolyl group or a carboxy group, or a pharmaceutically acceptable salt thereof.

7. A nitrogen-containing heterocyclic compound as claimed in claim 6, wherein R^1C represents a cyano group, or a pharmaceutically acceptable salt thereof.

8. A nitrogen-containing heterocyclic compound as claimed in claim 6, wherein R³ represents a carboxy group, or a pharmaceutically acceptable salt thereof.

9. A pharmaceutical composition comprising a nitrogen-containing heterocyclic compound as claimed in claim 1 or a pharmaceutically acceptable salt thereof as an active ingredient.

10. A pharmaceutical composition as claimed in claim 9, which is a xanthine oxidase inhibitor.

11. A pharmaceutical composition as claimed in claim 9, which is an uricosuric agent.

12. A pharmaceutical composition as claimed in claim 9, which is an agent for the treatment of gout or hyperuricemia.

13. A pharmaceutical composition as claimed in claim 9, which is an agent for the treatment of ischemic-reperfusion disorder, inflammatory disease, diabetes, cancer, arteriosclerosis or neurological disease.