An anti-tumor compound based on activating jwa gene and degrading her2, its preparation method and its application

A compound and anti-tumor technology, applied in the field of anti-tumor drugs, can solve problems such as ineffectiveness, achieve broad application prospects, and significantly treat tumors.

Active Publication Date: 2021-08-03
NANJING SIMCERE DONGYUAN PHARM CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, only about 50% of HER2-positive patients respond to targeted therapy, and for HER2 + Almost ineffective in metastatic BC (mBC)

Method used

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  • An anti-tumor compound based on activating jwa gene and degrading her2, its preparation method and its application
  • An anti-tumor compound based on activating jwa gene and degrading her2, its preparation method and its application
  • An anti-tumor compound based on activating jwa gene and degrading her2, its preparation method and its application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0059] Preparation of 4-fluoro-N-(4-methoxybenzo[d]thiazol-2-yl)benzo[d]thiazol-2-amine:

[0060] In a 50mL dry eggplant-shaped bottle equipped with a spherical reflux condenser and a magnet, add 2-chloro-4-fluorobenzo[d]thiazole (1g, 5.3mmol), 4-methoxybenzo[d]thiazole -2-amine (0.96g, 5.3mmol), cuprous iodide (0.31g, 0.3mmol), potassium carbonate (1.47g, 10.6mmol), dimethyl sulfoxide (20ml), heated to 100°C, reaction 6 Hour. After the reaction, cool to room temperature, add water (60ml), ethyl acetate (30mL), extract 3 times, wash with water, wash with saturated brine, dry over anhydrous sodium sulfate, filter, and evaporate the solvent under reduced pressure to obtain a black solid, crude Product silica gel powder sand making, silica gel chromatographic column purification [eluent: V PE :V EA =5:1] to obtain a black solid, which was slurried several times with ethyl acetate or methanol to obtain a white solid compound (0.7 g, yield: 39%).

[0061] 1 H NMR (400MHz, DMSO...

Embodiment 2

[0064] Preparation of 4,7-difluoro-N-(4-methoxybenzo[d]thiazol-2-yl)benzo[d]thiazol-2-amine:

[0065] With reference to the method shown in Example 1, wherein "2-chloro-4-fluorobenzo[d]thiazole" was replaced by "2-chloro-4,7-difluorobenzo[d]thiazole", an off-white solid (1.1 g, yield: 57%).

[0066] 1 H NMR (400MHz, DMSO-d 6 ) δ 7.73 (d, J = 5.4Hz, 1H), 7.28-7.17 (m, 3H), 7.02 (d, J = 8.0Hz, 1H), 3.92 (s, 3H).

[0067] ESI-MS m / z:350.1{[M+H] +}.

Embodiment 3

[0069] Preparation of 4,6-difluoro-N-(4-methoxybenzo[d]thiazol-2-yl)benzo[d]thiazol-2-amine:

[0070] With reference to the method shown in Example 1, wherein "2-chloro-4-fluorobenzo[d]thiazole" is replaced by "2-chloro-4,6-difluorobenzo[d]thiazole", an off-white solid (0.8 g, yield: 45%).

[0071] 1H NMR (400MHz, DMSO-d 6 )δ7.65(d, J=5.8Hz, 1H), 7.35(d, J=7.9Hz, 1H), 7.28-7.17(m, 2H), 7.03(d, J=8.0Hz, 1H), 3.92( s, 3H).

[0072] ESI-MS m / z:350.1{[M+H] +}.

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Abstract

The invention relates to an anti-tumor compound based on activating JWA gene and degrading HER2, its preparation method and application. The antitumor compound is a compound of formula I. The preparation method is to use two compounds to synthesize the compound of formula I through one-step reaction. The use is for preparing JWA gene activators or antitumor drugs. The antitumor compound of the present invention and its pharmaceutically acceptable salt can effectively activate the expression of JWA protein, and further specifically degrade the overexpressed HER2 protein through cascade activation of E3 ubiquitinase, thereby inhibiting the proliferation and growth of tumor cells in vivo.

Description

technical field [0001] The invention relates to an anti-tumor compound, which exerts an anti-tumor effect based on activating JWA gene and degrading HER2, and also relates to a preparation method and application of the compound, belonging to the field of anti-tumor drugs. Background technique [0002] Malignant tumor (cancer) is a major public health problem that seriously threatens the health of the Chinese population. According to statistics released by the National Cancer Center in 2019, the death of malignant tumors accounted for 23.91% of all residents' deaths, and the incidence and death of malignant tumors have continued to rise in the past decade, and the annual medical expenses caused by malignant tumors exceed 220 billion. The prevention and control situation is grim. Compared with historical data, the burden of cancer continues to rise. Over the past 10 years, the incidence of malignant tumors has maintained an annual increase of about 3.9%, and the mortality ra...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D277/82A61P35/00A61K31/428
CPCC07D277/82A61P35/00C07D417/12
Inventor 周建伟任彦霖陈冬寅黄叶飞李爱萍
Owner NANJING SIMCERE DONGYUAN PHARM CO LTD
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