WO2008087461B1 - Use of kynurenic acid and derivatives thereof in the treatment of conditions of the gastrointestinal tract accompanied by hypermotility and inflammation or gout or multiple sclerosis - Google Patents

Abstract

The subject of the invention is the use of kynurenic acid (KYNA) and its derivatives and physiologically acceptable salts of the general formula (I) in the manufacture of a medicament for the treatment of conditions characterized by pathophysiological conditions of the GI tract accompanied by increased motility and an elevated activity of the enzyme xanthine oxidoreductase (XOR), and further for the treatment of gout or multiple sclerosis. The meanings of the substituents of general formula (I) are defined in the claims.

Claims

20AMENDED CLAIMS received by the International Bureau on 08 September 2008 (08.09.2008)

1. Kynurenic acid derivatives of general formula (T) and pharmaceutically acceptable salts thereof, - wherein in the general formula Q)

G)

^■ R¹ is a hydroxy group, an NHR² group, an NR²R² group, or a C_1-10 straight or branched chain alkoxy or glyceryl group;

^■ R² is hydrogen atom or a C_1-10 straight or branched chain alkyl group;

^■ R³-R⁶ are independently of each other hydrogen atom, halogen atom, C_1-10 alkyl, alkenyl or alkynyl group optionally substituted with a halogen atom, with the exception of 7-chloro-kynurenic acid for use in the treatment of conditions characterized by hypermotility of the GI tract, or gout.

2. Kynurenic acid derivatives of general formula (I) and pharmaceutically acceptable salts thereof,

- wherein in the general formula (I)

G) ^■ R¹ is a hydroxy group, an NHR² group, an NR²R² group, or a C_1-10 straight or branched chain alkoxy or glyceryl group;

^■ R² is hydrogen atom or a C_1-10 straight or branched chain alkyl group;

^■ R³-R⁶ are independently of each other hydrogen atom, a C_1-10 alkyl, alkenyl or alkynyl group optionally substituted with a halogen atom, or halogen atom, for use in the treatment of conditions characterized by hypermotility of the GI tract or gout.

3. Compounds for use according to claim 1 or 2, wherein the condition to be treated is selected from Crohn's disease, colitis ulcerosa, diseases with post-ischemic reperfusion injuries of the GI tract, irritable bowel syndrome.

4. Compounds for use according to claim 1 or 2, wherein in the general formula (T)

(I)

^■ R¹ is hydroxy group, an NHR² group, an NR²R² group or a C_1-5 straight or branched chain alkoxy group or glyceryl group;

^■ R² is a hydrogen atom or a C₁-_S straight or branched chain alkyl group;

^■ R³-R⁶ are independently of each other a hydrogen atom, C_1-5 alkyl, alkenyl or alkynyl group optionally substituted with a halogen atom, or halogen atom, with the exception of 7-chloro-lcynurenic acid.

5. Compounds for use according to claim 1 or 2, wherein in the general formula (T)

G) 22

■ R¹ is hydroxy group, an NH₂, NH-(C_1-5 straight or branchedchain alkyl) group or C_1-5 straight or branched-chain alkoxy or glyceryl group,

■ R² is a hydrogen atom, R³-R⁶ are independently of each other a hydrogen atom or a halogen atom, or CF₃ group, with the exception of 7-chloro-kynurenic acid.

6. Compounds for use according to claim 1 or 2, wherein the compound of general formula (I) is kynurenic acid (4-hydroxyquinoline-2-carboxylic acid), or a pharmaceutically acceptable salt, ester or amide thereof, such as the glyceryl ester.

7. Method for treating conditions characterized by hypermotility of the GI tract or gout, characterized by administering to the patient kynurenic acid derivatives of the general formula (I) or pharmaceutically salts thereof, wherein in the general formula (T)

(I)

• R¹ is a hydroxy group, an NHR² group, an NR²R² group, or a C_1-10 straight or branched chain alkoxy group or glyceryl group;

• R² is a hydrogen atom or a C_1-10 straight or branched chain alkyl group;

■ R³-R⁶ are independently of each other hydrogen atom, a C_1-10 alkyl, alkenyl or alkynyl group optionally substituted with a halogen atom, or halogen atom with the exception of 7-chloro-lcynurenic acid.

8. Method of claim 7, characterized in that the condition or disease to be treated is, Crohn's disease, colitis ulcerosa, diseases with post-ischemic reperfusion injuries of the GI tract, irritable bowel syndrome, gout.