2-Phenylthiophene Derivative

• US 20080027048A1
• Filed: 08/26/2005
• Published: 01/31/2008
• Est. Priority Date: 08/27/2004
• Status: Active Grant

• Current Assignee: Astellas Pharma Incorporated
• Original Assignee: Astellas Pharma Incorporated
• Inventors: Kamikawa, Akio, Yokota, Masaki, Hattori, Kazuyuki, Kawakami, Masakatsu, Naito, Ryo, Miyata, Junji
• Granted Patent: US 7,612,108 B2
• Time in Patent Office: Days
• US Class Current: 514/231.5
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 19/06 Antigout agents, e.g. antihyperuricemic or uricosuric agents
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• 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 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 333/40 Thiophene-2-carboxylic acid
• CPC Class Codes: C07D 409/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 409/10 linked by a carbon chain containing aromatic rings
• CPC Class Codes: C07D 417/10 linked by a carbon chain containing aromatic rings
• CPC Class Codes: C07D 417/12 linked by a chain containing hetero atoms as chain links

Abstract

The present invention relates to a 2-phenylthiophene derivative or a salt thereof, wherein the thiophene ring is substituted with a carboxyl group or the like and the benzene ring has an electron-withdrawing group such as a cyano group and an electron-donating group such as a substituted alkoxy group at the same time. Since the compound of the invention has good xanthine oxidase-inhibitory action and uric acid-lowering action and does not have a structure derived from nucleic acid, the compound has advantages of high safety and excellent effects as compared with conventional compounds and is useful as a therapeutic or preventive agent for hyperuricemia, gout, inflammatory bowel diseases, diabetic kidney diseases, diabetic retinopathy, or the like.

Claims

1. A derivative represented by the following general formula (I) or a salt thereof:

2. The derivative according to claim 1 represented by the following general formula (I^A) or a salt thereof:

3. The derivative according to claim 2 or a salt thereof, wherein R¹ is —

CO₂H.

4. The derivative according to claim 3 or a salt thereof, wherein R⁴ is —

CN.

5. The derivative according to claim 4 or a salt thereof, wherein X is —

O—

.

6. The derivative according to claim 4 or a salt thereof, wherein X is —

N(R⁷)—

.

7. The derivative according to claim 5 or a salt thereof, wherein R⁶ is a linear or branched alkyl group having 2 to 6 carbon atoms, cycloalkyl having 3 to 6 carbon atoms, or -lower alkylene-(cycloalkyl having 3 to 6 carbon atoms).

8. The derivative according to claim 6 or a salt thereof, wherein R⁷ and R⁶ may be combined together with the adjacent nitrogen atom to form a nitrogen-containing saturated heterocycle which may be substituted with lower alkyl.

9. The derivative according to claim 1 selected from the group consisting of 5-(3-cyano-4-n-propoxyphenyl)thiophene-2-carboxylic acid, 5-(3-cyano-4-isobutoxyphenyl)thiophene-2-carboxylic acid, 5-(4-isobutoxy-3-nitrophenyl)thiophene-2-carboxylic acid, 5-(4-[butyl(methyl)amino]-3-cyanophenyl}thiophene-2-carboxylic acid, 5-(3-cyano-4-piperidin-1-ylphenyl)thiophene-2-carboxylic acid, 5-(3-cyano-4-isobutoxyphenyl)-3-fluorothiophene-2-carboxylic acid, 5-[3-cyano-4-(cyclopentyloxy)phenyl]-3-fluorothiophene-2-carboxylic acid, 5- (4-[(E)-cinnamyloxy]-3-cyanophenyl)-3-fluorothiophene-2-carboxylic acid, 5-(3-cyano-5-fluoro-4-isobutoxyphenyl)thiophene-2-carboxylic acid, or a pharmaceutically acceptable salt thereof.

10. A pharmaceutical composition comprising the derivative according to claim 1 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.

11. The pharmaceutical composition according to claim 10, which is a xanthine oxidase inhibitor.

12. The pharmaceutical composition according to claim 10, which is a preventive or therapeutic agent for hyperuricemia, gout, inflammatory bowel diseases, diabetic kidney diseases, or diabetic retinopathy.

13. Use of the derivative according to claim 1 or a pharmaceutically acceptable salt thereof for the production of a preventive or therapeutic agent for hyperuricemia, gout, inflammatory bowel diseases, diabetic kidney diseases, or diabetic retinopathy.

14. A preventive or therapeutic method of hyperuricemia, gout, inflammatory bowel diseases, diabetic kidney diseases, or diabetic retinopathy, which comprises administering a therapeutically effective amount of the derivative according to claim 1 or a pharmaceutically acceptable salt thereof to a patient.