5-Pyridine-1H-indazole compounds, pharmaceutical compositions and uses

Abstract

The present invention discloses a 5-pyridine-1H-indazole compound, pharmaceutical composition and use. The structure of the compound is as shown in formula I or II, and further includes its isomer, pharma-ceutical acceptable salt, or mixture thereof. The compound and its pharmaceutical composition can effectively inhibit the activity of CLK2 protein and DYRK1A protein, and can be prepared as a drug for treating osteoarthritis, and can exert its efficacy at the molecular level, and the therapeutic effect is better, and the optimal level can reach nanomolar concentration. In addition, the preparation method of the compound is simple and easy to operate. [C72] TIFF2025515926000083.tif25166

Claims

1. A 5-pyridine-1H-indazole compound having the structure of formula I or II, wherein the compound further comprises its stereoisomers, pharmaceutically acceptable salts, or mixtures thereof. 【Transformation 68】 In the formula, R １ This refers to hydrogen, straight-chain or branched-chain carbon. １ ~C １０ A group selected from alkyl groups, phenyl groups, 4- to 6-membered heterocycles, or 4- to 6-membered ring groups, wherein the group excluding hydrogen may be substituted with one or more substituents selected from the group consisting of halogens, methoxy groups, trifluoromethyl groups, nitro groups, hydroxyl groups, amino groups, azide groups, sulfonic acid groups, and 3- to 6-membered rings. L and M are -CH ２ -, -NH-, -O-, or a chemical bond, R ２ teeth, 【Transformation 69】 Selected based on this principle, R ３ is hydrogen or C １ ~C ４ Selected from alkyl groups, A 5-pyridine-1H-indazole compound characterized by the following features.

2. In the above structure, R １ is selected from an isobutyl group, a cyclopropylmethyl group, a cyclopentyl group, an α - aminoisopentyl group, a 3,3 - difluorotetrahydropyrrolyl group, hydrogen, a morpholinyl group, a methyl group, or a tert - butyl group, R ２ teeth, 【Transformation 70】 The compound according to claim 1, characterized in that it is selected from the following group.

3. The compound according to claim 1, characterized in that it is selected from any one of the following compounds. 【Chemistry 71】 【change】 【change】 【change】

4. The pharmaceutically acceptable salts are salts formed by the compound with an acid such as hydrochloric acid, sulfuric acid, phosphoric acid, carbonic acid, nitric acid, hydrobromic acid, hydroiodic acid, maleic acid, fumaric acid, tartaric acid, citrate, malic acid, methanesulfonic acid, p-toluenesulfonic acid, naphthalenesulfonic acid, succinic acid, acetic acid, mandelic acid, isobutyric acid, or malonic acid. The compound according to feature 1.

5. A compound comprising any one of claims 1 to 4 and a pharmaceutically acceptable carrier, A pharmaceutical composition characterized by the following features.

6. In the production of a CLK2 protein inhibitor drug of any one of claims 1 to 4, use.

7. In the production of a DYRK1A protein inhibitor drug using any one of claims 1 to 4, use.

8. In the production of a CLK2 protein inhibitor drug using the pharmaceutical composition described in Claim 5, use.

9. In the production of a DYRK1A protein inhibitor drug using the pharmaceutical composition described in Claim 5, use.

10. The aforementioned drug is a drug used to treat inflammation. The use described in feature 6.

11. The aforementioned drug is a drug used to treat inflammation. The use described in feature 7.

12. The aforementioned drug is a drug used to treat inflammation. The use described in feature 8.

13. The aforementioned drug is a drug used to treat inflammation. The use described in feature 9.

14. The inflammation is due to osteoarthritis, tendon disorders, or rheumatoid arthritis. The use described in feature 10.

15. The inflammation is due to osteoarthritis, tendon disorders, or rheumatoid arthritis. The use described in feature 11.

16. The inflammation is due to osteoarthritis, tendon disorders, or rheumatoid arthritis. The use described in feature 12.

17. The inflammation is due to osteoarthritis, tendon disorders, or rheumatoid arthritis. The use described in feature 13.

18. The aforementioned compound has a cartilage-protective effect. The use described in feature 14.

19. The aforementioned compound has a cartilage-protective effect. The use described in feature 15.

20. The aforementioned compound has a cartilage-protective effect. The use described in feature 16.

21. The aforementioned compound has a cartilage-protective effect. The use described in feature 17.

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