Compound used as CDK7 kinase inhibitor and application thereof

A kind of kinase inhibitor and compound technology, applied in the field of medicine

Inactive Publication Date: 2021-04-16
TYK MEDICINES INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Especially in small cell lung cancer, triple-negative breast cancer, pancreatic cancer and other major unmet diseases that currently lack effective treatments

Method used

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  • Compound used as CDK7 kinase inhibitor and application thereof
  • Compound used as CDK7 kinase inhibitor and application thereof
  • Compound used as CDK7 kinase inhibitor and application thereof

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0188] The present invention also provides a preparation method of a pharmaceutical composition, comprising the steps of: mixing a pharmaceutically acceptable carrier with the compound of general formula I of the present invention or its crystal form, pharmaceutically acceptable salt, hydrate or solvate substances are mixed to form a pharmaceutical composition.

[0189] The present invention also provides a treatment method, which comprises the steps of: administering the compound of formula I described in the present invention, or its crystal form, pharmaceutically acceptable salt, hydrate or solvate, or administering The pharmaceutical composition of the present invention is used for inhibiting CDK7.

[0190] Compared with the prior art, the present invention has the following main advantages:

[0191] (1) The compound of the present invention has excellent inhibitory ability to CDK7 kinase;

[0192](2) The compound of the present invention has lower toxic and side effects...

Embodiment

[0197] The technical solution of the present invention will be further described below, but the protection scope of the present invention is not limited thereto.

[0198] Synthesis of Intermediate 1

[0199] The structural formula of intermediate 1 is as follows:

[0200]

[0201] The experimental process is as follows:

[0202] The synthetic route is as follows:

[0203]

[0204] Synthetic steps:

[0205] (1) Synthesis of compound 2

[0206] Dissolve 175g (1.0eq) of compound 1 in tert-butanol, stir at room temperature, add triethylamine to the reaction solution, the solution changes from clear yellow to clear reddish brown, under nitrogen protection, slowly add DPPA (1.5eq) dropwise, and Slowly raise the temperature of the reaction system to 80°C, and at the same time, a large number of bubbles will be generated. After the bubbles were reduced, the reaction was continued at 80°C for 3 hours, then an aqueous solution of sodium carbonate was added to quench the react...

Embodiment T-01

[0265] The synthetic compound of the present invention:

[0266]

[0267] The experimental process is as follows:

[0268] The synthetic route is as follows:

[0269]

[0270] Synthetic steps:

[0271] (1) Synthesis of Compound 2

[0272] Add 11.5g (1.0eq) compound 1, 18.4g (1.4eq) DPPA, 8.7g (1.8eq) triethylamine, 100ml dioxane in a 250ml three-necked flask, react at 80°C under nitrogen protection for 1h, add 3.5ml ( 2.0eq) methanol, continue to react for 3h. TLC monitored the reaction to complete. Water was added, extracted with EA, and purified by column to obtain 9.2 g of white solid.

[0273] (2) Synthesis of compound 3

[0274] In a 500ml three-necked flask, add 8g (1.0eq) compound 1, 12.7g (2.0eq) 2,4-dichloro-5-trifluoromethylpyrimidine, 6.8g (1.7eq) aluminum trichloride, 400mlDCE, nitrogen protection React overnight at 80°C. TLC monitored the reaction to complete. Add water to quench the reaction, separate the aqueous phase and add EA to extract, combin...

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Abstract

The invention relates to a compound used as a CDK7 kinase inhibitor and application thereof. Specifically, the compound disclosed by the invention has a structure shown as a formula I, and the definitions of all groups and substituents are as described in the specification. The compounds of the present invention are useful as inhibitors of cyclin-dependent kinase 7 (CDK7) for the treatment or prevention of proliferative diseases such as cancer, especially for modulating and treating diseases associated with abnormal activity of cyclin-dependent kinase 7 (CDK7).

Description

technical field [0001] The invention relates to the field of medical technology, in particular to a compound used as a CDK7 kinase inhibitor, and its application in regulating CDK7 kinase activity or treating CDK7-related diseases, especially cancer. Background technique [0002] Cyclin-dependent kinases CDKs (Cyclin-dependent kinases) belong to the serine / threonine kinase family, which combine with the corresponding cell cycle proteins (Cyclins) to form active dimer complexes to exert physiological functions and cause cell growth and added value. At present, more than 20 kinds of CDKs have been found, which are divided into two categories according to their functions: CDKs that regulate cell cycle and CDKs that regulate cell transcription, among which CDKs 1-6 and 14-18 are involved in the regulation of cell cycle, and CDKs 7-13 and 19- 20 is involved in the transcriptional regulation of cells. [0003] CDK7 is an important member of the CDKs family, and its main physiolo...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D401/14C07D403/14C07D413/14C07D487/04C07F9/6558C07F9/6561C07F9/6568C07F9/6574A61P3/00A61P9/00A61P29/00A61P31/00A61P35/00A61P35/02A61P37/02A61K31/675A61K31/5025A61K31/506
CPCC07F9/65685C07F9/65583C07D401/14C07D403/14C07D413/14C07D487/04C07F9/6561C07F9/65616C07F9/657172C07F9/657181A61P35/00A61P35/02A61P29/00A61P9/00A61P31/00A61P37/02A61P3/00A61K31/5025A61K31/506A61K31/675C07D403/04C07D405/14C07D417/14C07D471/04C07D491/048
Inventor 梁阿朋李钧董胜利吴豫生李美华牛成山徐宇
Owner TYK MEDICINES INC
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