Histone deacetylases inhibitor

Abstract

The invention provides a histone deacetylases (HDACs) inhibitor compound N<1>-(6-(hydroxyamino)-6-oxohexyl)-N<4>-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)terephthalamide having an obvious inhibitory effect on both HDACs and human leukemia U937 cell growth and proliferation, wherein the inhibitory effect is significantly stronger than that of a common HDACs inhibitor trichostatin TSA. The invention also provides a preparation method and a process route of the compound.

Description

Technical field

[0001] The invention relates to a histone deacetylase inhibitor and a preparation method thereof, belonging to the field of medicine. Background technique

[0002] Tumor occurrence is a complex pathological process, affected by multiple factors, including individual genetic factors, environmental factors, physical and chemical factors, molecular biological factors and so on. With the rapid development of life sciences and the in-depth development of molecular biology research on the pathogenic mechanism and pathogenesis of tumors, the prominent role of molecular biological factors in tumorigenesis has been gradually revealed. The inactivation of various factors regulating growth and proliferation becomes the key inducement of tumorigenesis. Therefore, the study of molecular biology on the pathogenicity and pathogenesis of tumors provides a basis for the development of low-toxicity and high-efficiency anti-tumor drugs targeting specific molecular targets [Xie...

Examples

Embodiment Construction

[0010] One, synthesis embodiment

[0011] 1. Synthesis process: as shown in Figure 1.

[0012] 2. Experimental operation

[0013] (1) Synthesis of 2,5-dichloro-2,5-dimethylhexane

[0014] 2,5-Dimethyl-2,5-hexanediol (7.31g, 50mmol) was added to 12mol / L hydrochloric acid (60ml), heated to 85°C and stirred for 1h, cooled to room temperature, filtered with suction, and the filter cake was dissolved in Dichloromethane, washed with water until neutral, dried over anhydrous magnesium sulfate, filtered, the filtrate was evaporated to remove dichloromethane, and the residue was dried at room temperature under reduced pressure (0.7-13.3Pa) to obtain a white powdery solid 2,5-bis Chloro-2,5-dimethylhexane (7.50 g, 81.88%).

[0015] (2) 1,2,3,4-tetrahydro-1,1,4,4-tetramethylnaphthalene

[0016] Add 2,5-dichloro-2,5-dimethylhexane (7.32g, 40mmol) to benzene (80ml, 900mmol), add anhydrous aluminum chloride (0.53g, 4mmol) under stirring, and heat The reaction solution was refluxed for ...

Technical field

[0001] The invention relates to a histone deacetylase inhibitor and a preparation method thereof, belonging to the field of medicine. Background technique

[0002] Tumor occurrence is a complex pathological process, affected by multiple factors, including individual genetic factors, environmental factors, physical and chemical factors, molecular biological factors and so on. With the rapid development of life sciences and the in-depth development of molecular biology research on the pathogenic mechanism and pathogenesis of tumors, the prominent role of molecular biological factors in tumorigenesis has been gradually revealed. The inactivation of various factors regulating growth and proliferation becomes the key inducement of tumorigenesis. Therefore, the study of molecular biology on the pathogenicity and pathogenesis of tumors provides a basis for the development of low-toxicity and high-efficiency anti-tumor drugs targeting specific molecular targets [Xie...

Examples

Embodiment Construction

[0010] One, synthesis embodiment

[0011] 1. Synthesis process: as shown in Figure 1.

[0012] 2. Experimental operation

[0013] (1) Synthesis of 2,5-dichloro-2,5-dimethylhexane

[0014] 2,5-Dimethyl-2,5-hexanediol (7.31g, 50mmol) was added to 12mol / L hydrochloric acid (60ml), heated to 85°C and stirred for 1h, cooled to room temperature, filtered with suction, and the filter cake was dissolved in Dichloromethane, washed with water until neutral, dried over anhydrous magnesium sulfate, filtered, the filtrate was evaporated to remove dichloromethane, and the residue was dried at room temperature under reduced pressure (0.7-13.3Pa) to obtain a white powdery solid 2,5-bis Chloro-2,5-dimethylhexane (7.50 g, 81.88%).

[0015] (2) 1,2,3,4-tetrahydro-1,1,4,4-tetramethylnaphthalene

[0016] Add 2,5-dichloro-2,5-dimethylhexane (7.32g, 40mmol) to benzene (80ml, 900mmol), add anhydrous aluminum chloride (0.53g, 4mmol) under stirring, and heat The reaction solution was refluxed for ...

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