Novel compounds effective as xanthine oxidase inhibitors, method for preparing the same, and pharmaceutical composition containing the same.

Compounds of the following formula (1): in the above formula (1) A is selected from the following substituents A-i: wherein J represents hydrogen, E represents hydrogen, or cyano, D represents halogen, cyano, nitro, or -CHO, Q is selected from the following substituents Q-i, Q-ii and Q-iii-1; (Q-i) hydrogen; (Q-ii) C₁-C₈-alkyl which is unsubstituted or substituted by a group selected from halogen, hydroxy, C₃-C₇-cycloalkyl and O-R₆ wherein R₆ represents C₁-C₇alkyl; (Q-iii-1) (wherein W represents O or S, R7 represents hydrogen, or C₁-C₇-alkyl, and n denotes an integer of 0~3); Y represents hydrogen, saturated straight-chain or branched C₁-C₇-alkyl, C₁-C₇-alkoxy-C1-C7-alkyl or phenyl, and G represents hydrogen, or pharmaceutically acceptable salts thereof.

A compound of Claim 1 which is selected from the following group:

1. 1-(3-cyano-1-isopropyl-indol-5-yl)pyrazole-4-carboxylic acid;

2. 1-[3-cyano-1-(cyclopropylmethyl)indol-5-yl]pyrazole-4-carboxylic acid;

3. 1-[3-cyano-1-cyclopropyl-indol-5-yl]pyrazole-4-carboxylic acid;

4. 1-(3-cyano-1-isobutyl-indol-5-yl)pyrazole-4-carboxylic acid;

5. 1-[3-cyano-1-(2,2-dimethylpropyl)indol-5-yl]pyrazole-4-carboxylic acid;

6. 1-[3-cyano-1-(2-methoxyethyl)indol-5-yl]pyrazole-4-carboxylic acid;

7. 1-(3-cyano-1-sec-butyl-indol-5-yl)-pyrazole-4-carboxylic acid;

8. 1-[3-cyano-1-cyclobutyl-indol-5-yl]pyrazole-4-carboxylic acid;

9. 1-(3-cyano-1-cyclopentyl-indol-5-yl)-pyrazole-4-carboxylic acid;

10. 1-[3-cyano-1-(1-fluoropropan-2-yl)-indol-5-yl]-pyrazole-4-carboxylic acid;

11. 1-[3-cyano-1-(tetrahydrofuran-3-yl)-indol-5-yl]-pyrazole-4-carboxylic acid;

17. 1-(1-isopropyl-3-nitro-indol-5-yl)pyrazole-4-carboxylic acid; or pharmaceutically acceptable salts thereof.

A process for preparing the compounds of formula (1), or pharmaceutically acceptable salts thereof according to Claim 1 characterized by the following Reaction Scheme (1): in the above Reaction Scheme (1), A, D, E, G, Y and Q are as defined in Claim 1, provided that Q is not hydrogen, and L₁ represents a leaving group.

A process for preparing the compounds of formula (1) or pharmaceutically acceptable salts thereof according to Claim 1 characterized by the following Reaction Scheme (2): in the above Reaction Scheme (2), A, D, E, G and Y are as defined in Claim 1.

The process of Claim 4, wherein the compounds of formula (4) used as a starting material are prepared according to the following Reaction Scheme (3): in the above Reaction Scheme (3), A, E, G and Y are as defined in Claim 1.

A pharmaceutical composition for the inhibition of xanthine oxidase, which comprises (a) a therapeutically effective amount of the compounds of formula (1), pharmaceutically acceptable salts thereof according to Claim 1; and (b) pharmaceutically acceptable carriers, diluents, excipients or their combinations.

The composition of Claim 6, for use in the prevention or treatment of diseases associated with human xanthine oxidase selected from the group consisting of hyperuricemia, gout, heart failure, cardiovascular disease, hypertension, diabetes, complications of diabetes, kidney disease, inflammation, articular disease and inflammatory bowel disease.

The composition for use of Claim 7 wherein the complications of diabetes is selected from the group consisting of hyperlipidemia, atherosclerosis, obesity, hypertension, retinosis and renal failure.