Selenophenol quinoline derivative as well as preparation method and application thereof

Abstract

The invention discloses a selenophenol quinoline derivative as well as a preparation method and application thereof. The structure of the selenophenol quinoline derivative is shown as a formula I, a formula II or a formula III, wherein R1 is hydrogen, a C1-6 alkyl group, a C1-6 alkoxy group, a substituted ketone group, a phenyl group, a benzyl group, a substituted phenyl group or a substituted benzyl group; R1<+> is a monovalent metal cation; R2 is one or more of hydrogen, halogen, a C1-4 alkyl group, a C1-4 alkoxy group or a C1-4 haloalkyl group; R3 is a substituted five-membered heterocyclicring or a substituted six-membered heterocyclic ring; and a heteroatom is one or more of N, O, S or Se. The compound disclosed by the invention is novel in structure, simple in preparation process and relatively good in inhibition effect on various cancer cells, particularly the compounds 34, 44, 45, 98, 104, 115 and 116 have excellent inhibition effects on various cancer cells, the effects of the compounds are equivalent to those of a positive control DDP, and the compounds can be used to prepare anti-cancer drugs to be applied under 5 [mu]M or below, so that the prospect is wide.

Description

technical field

[0001] The present invention relates to the technical field of medicinal chemistry, and more specifically, relates to a selenophenoquinoline derivative and a preparation method and application thereof. Background technique

[0002] Selenium is considered to be an indispensable trace element for maintaining normal physiological functions of the human body. The human body cannot synthesize or store selenium itself, and can only obtain it through food intake from the outside world. The scientific community generally believes that selenium achieves various physiological functions by forming selenoproteins with proteins in the body. Common selenoproteins are: Se-dependent glutathione peroxidases (GPxs), cellular oxidoreductases thioredoxin reductases (TRs) and those required for energy metabolism Iodothyronine deiodinases (TDIs).

[0003] Hydrogen peroxide and phospholipid hydroxide can generate various reactive oxygen species (ROS) in cells, and ROS is conside...

Examples

Embodiment 1

[0042] The preparation of embodiment 1 compound XM_A0032

[0043] The preparation process of compound XM_A0032 is as follows:

[0044]

[0045] Weigh 0.2g of QM15 in a 25mL two-neck flask, add Pd(PPh 3 ) 2 Cl 2 35mg and lithium chloride 140mg, seal the reaction device, replace the argon protection; add anhydrous THF 5mL, stir at room temperature for 10min, add 2-tributylstannylthiophene 0.41mL, heat in an oil bath at 85°C, and react overnight. Cool to room temperature, add 50 mL of ethyl acetate and 100 mL of water, shake well, separate the organic phase, extract the water phase with ethyl acetate (20 mL×2), combine the organic phases, and wash with saturated NaCl solution (150 mL ×2); anhydrous MgSO 4 Dry, filter, and evaporate the solvent under reduced pressure. After separation and purification by flash column chromatography (15% EA / PE), the solvent was evaporated under reduced pressure to obtain 232 mg of a yellow solid. (XM013-LG02, P93) Yield: 94%.

[0046] 1...

Embodiment 2

[0048] Preparation of Example 2 Compound XM_A0033

[0049] The preparation process of compound XM_A0033 is as follows:

[0050]

[0051] Weigh 0.3g of QM13 in a 25mL two-necked flask, add Pd(PPh 3 ) 2 Cl 2 35mg and lithium chloride 136mg, seal the reaction device, replace the argon protection; add anhydrous THF 5mL, stir at room temperature for 10min, add 2-tributylstannylthiophene 0.4mL, heat in an oil bath at 85°C, and react overnight. Cool to room temperature, add 50 mL of ethyl acetate and 100 mL of water, shake well, separate the organic phase, extract the water phase with ethyl acetate (20 mL×2), combine the organic phases, and wash with saturated NaCl solution (150 mL ×2); anhydrous MgSO 4 Dry, filter, and evaporate the solvent under reduced pressure. After separation and purification by flash column chromatography (10% EA / PE), the solvent was evaporated under reduced pressure to obtain 340 mg of a yellow solid. Yield: 98%.

[0052] 1 H NMR (400MHz, CDCl 3 ...

Embodiment 3

[0055] The preparation of embodiment 3 compound XM_A0034

[0056] The preparation process of compound XM_A0034 is as follows:

[0057]

[0058] Weigh 50mg of QM03 in a 25mL two-neck flask, add Pd(PPh 3 ) 2 Cl 2 25mg and lithium chloride 38mg, seal the reaction device, replace the argon protection; add anhydrous THF 3mL, stir at room temperature for 10min, add 2-tri-n-butylstannylpyridine 0.11mL, heat in an oil bath at 85°C, and react overnight. Cool to room temperature, add 50 mL of ethyl acetate and 100 mL of water, shake well, separate the organic phase, extract the water phase with ethyl acetate (20 mL×2), combine the organic phases, and wash with saturated NaCl solution (150 mL ×2); anhydrous MgSO 4 Dry, filter, and evaporate the solvent under reduced pressure. After separation and purification by flash column chromatography (5% EA / PE), the solvent was evaporated under reduced pressure to obtain 30 mg of yellow oil. Yield: 49.5%.

[0059] 1 H NMR (400MHz, CDCl ...

technical field

[0001] The present invention relates to the technical field of medicinal chemistry, and more specifically, relates to a selenophenoquinoline derivative and a preparation method and application thereof. Background technique

[0002] Selenium is considered to be an indispensable trace element for maintaining normal physiological functions of the human body. The human body cannot synthesize or store selenium itself, and can only obtain it through food intake from the outside world. The scientific community generally believes that selenium achieves various physiological functions by forming selenoproteins with proteins in the body. Common selenoproteins are: Se-dependent glutathione peroxidases (GPxs), cellular oxidoreductases thioredoxin reductases (TRs) and those required for energy metabolism Iodothyronine deiodinases (TDIs).

[0003] Hydrogen peroxide and phospholipid hydroxide can generate various reactive oxygen species (ROS) in cells, and ROS is conside...

Examples

Embodiment 1

[0042] The preparation of embodiment 1 compound XM_A0032

[0043] The preparation process of compound XM_A0032 is as follows:

[0044]

[0045] Weigh 0.2g of QM15 in a 25mL two-neck flask, add Pd(PPh 3 ) 2 Cl 2 35mg and lithium chloride 140mg, seal the reaction device, replace the argon protection; add anhydrous THF 5mL, stir at room temperature for 10min, add 2-tributylstannylthiophene 0.41mL, heat in an oil bath at 85°C, and react overnight. Cool to room temperature, add 50 mL of ethyl acetate and 100 mL of water, shake well, separate the organic phase, extract the water phase with ethyl acetate (20 mL×2), combine the organic phases, and wash with saturated NaCl solution (150 mL ×2); anhydrous MgSO 4 Dry, filter, and evaporate the solvent under reduced pressure. After separation and purification by flash column chromatography (15% EA / PE), the solvent was evaporated under reduced pressure to obtain 232 mg of a yellow solid. (XM013-LG02, P93) Yield: 94%.

[0046] 1...

Embodiment 2

[0048] Preparation of Example 2 Compound XM_A0033

[0049] The preparation process of compound XM_A0033 is as follows:

[0050]

[0051] Weigh 0.3g of QM13 in a 25mL two-necked flask, add Pd(PPh 3 ) 2 Cl 2 35mg and lithium chloride 136mg, seal the reaction device, replace the argon protection; add anhydrous THF 5mL, stir at room temperature for 10min, add 2-tributylstannylthiophene 0.4mL, heat in an oil bath at 85°C, and react overnight. Cool to room temperature, add 50 mL of ethyl acetate and 100 mL of water, shake well, separate the organic phase, extract the water phase with ethyl acetate (20 mL×2), combine the organic phases, and wash with saturated NaCl solution (150 mL ×2); anhydrous MgSO 4 Dry, filter, and evaporate the solvent under reduced pressure. After separation and purification by flash column chromatography (10% EA / PE), the solvent was evaporated under reduced pressure to obtain 340 mg of a yellow solid. Yield: 98%.

[0052] 1 H NMR (400MHz, CDCl 3 ...

Embodiment 3

[0055] The preparation of embodiment 3 compound XM_A0034

[0056] The preparation process of compound XM_A0034 is as follows:

[0057]

[0058] Weigh 50mg of QM03 in a 25mL two-neck flask, add Pd(PPh 3 ) 2 Cl 2 25mg and lithium chloride 38mg, seal the reaction device, replace the argon protection; add anhydrous THF 3mL, stir at room temperature for 10min, add 2-tri-n-butylstannylpyridine 0.11mL, heat in an oil bath at 85°C, and react overnight. Cool to room temperature, add 50 mL of ethyl acetate and 100 mL of water, shake well, separate the organic phase, extract the water phase with ethyl acetate (20 mL×2), combine the organic phases, and wash with saturated NaCl solution (150 mL ×2); anhydrous MgSO 4 Dry, filter, and evaporate the solvent under reduced pressure. After separation and purification by flash column chromatography (5% EA / PE), the solvent was evaporated under reduced pressure to obtain 30 mg of yellow oil. Yield: 49.5%.

[0059] 1 H NMR (400MHz, CDCl ...

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