CN105541823A - Oxazoline-ring-containing triazine compounds and preparation method thereof, and application of oxazoline-ring-containing triazine compounds in anticancer drugs - Google Patents

Oxazoline-ring-containing triazine compounds and preparation method thereof, and application of oxazoline-ring-containing triazine compounds in anticancer drugs Download PDF

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CN105541823A
CN105541823A CN201610075852.6A CN201610075852A CN105541823A CN 105541823 A CN105541823 A CN 105541823A CN 201610075852 A CN201610075852 A CN 201610075852A CN 105541823 A CN105541823 A CN 105541823A
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CN105541823B (en
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李德江
李玉姣
汪洪波
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Hubei weidehe Innovative Material Technology Co.,Ltd.
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China Three Gorges University CTGU
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links

Abstract

The invention relates to oxazoline-ring-containing triazine compounds and a preparation method thereof, and application of the oxazoline-ring-containing triazine compounds in anticancer drugs. The invention discloses oxazoline-ring-containing triazine compounds with anticancer activity, and a preparation method and application thereof. The core structure segments of oxazolines and triazines are reasonably assembled and modified, so that the synthesized oxazoline-ring-containing triazine compounds have high inhibition activity for in-vitro growth of liver cancer cell (HepG-2) strains, lung cancer cell (A549-1) strains and mammary cancer cell (231-2) strains.

Description

A kind of compound in triazine class of Han oxazoline ring, preparation method and the application on cancer therapy drug thereof
Technical field
The present invention relates to preparation method and the Structural Identification of the compound in triazine class with antitumour activity Han oxazoline ring, this compounds, to the growth in vitro of liver cancer cell (HepG-2), lung carcinoma cell (A549-1) cell and breast cancer cell (231-2) three kinds of JEG-3, has inhibit activities.
Background technology
1,3,5-triazines analog derivative has anti-trypanosome activity, anti-inflammatory activity, anti-microbial activity, anti-retroviral activity, cytotoxic activity and neovascularization inhibiting activity, especially antitumour activity and cause the extensive research of chemistry and medicine expert.Oxazoline compounds due to its widely biological activity as anti-tumor activity, hypotensive effect, desinsection, sterilization, anti AIDS virus and the biological activity such as anticonvulsion and widely application prospect quite by the favor of people.In view of 1,3,5-triazines with the good biological activity of oxazoline pharmacophore, utilize the active group splicing principle of medicinal design, on 1,3,5-triazines ring, Yin Ru oxazoline is to realizing active superposition, filters out the compound of active higher antitumour activity.
Summary of the invention
The object of the present invention is to provide the compound in triazine class containing oxazoline ring, the chemical structure of general formula of this compounds is as follows:
In formula: Ar is any one in phenyl, 4-fluorophenyl, 4-chloro-phenyl-, 3-chloro-phenyl-, 3-nitrophenyl, 4-nitrophenyl, 4-aminomethyl phenyl;
Wherein, when Ar is phenyl, be compounds Ⅳ a; When Ar is 4-fluorophenyl, when to be compounds Ⅳ b, Ar be 4-chloro-phenyl-, to be compounds Ⅳ c, Ar be 3-chloro-phenyl-is, when to be compounds Ⅳ d, Ar be 3-nitrophenyl, when to be compounds Ⅳ e, Ar be 4-nitrophenyl, when to be compounds Ⅳ f, Ar be 4-aminomethyl phenyl, be compounds Ⅳ g.
The described preparation method with the compound in triazine class of antitumour activity Han oxazoline ring, comprises the following steps:
A: in the mixing solutions of acetone-water (volume ratio is 1:1), adds phenol, sodium hydroxide, cyanuric chloride, after control temperature reacts 6-10 hour at 10-30 DEG C, after reaction terminates, reaction solution is poured in frozen water, stir 10min, suction filtration, filter cake deionized water drip washing 3-4 time, 50 DEG C of vacuum-dryings, obtain white powdery solids, be intermediate I, reaction equation is as follows:
B: under nitrogen protection; be equipped with in the flask of thermometer, constant pressure funnel, reflux condensing tube and drying tube and first add mineral alkali, 4-hydroxy benzaldehyde and DMF, after reaction 2h; add intermediate I; stirring at room temperature 20-24h, after reaction terminates, pours into reaction solution in deionized water; stir; suction filtration, filter cake deionized water wash 3-4 time, is placed in vacuum drying oven dry.Obtain white powdery solids, be intermediate II, reaction equation is as follows:
C: under nitrogen protection, in organic mixed solvent, adds intermediate II, aryl formyl hydrazine, reaction 10-15 hour.After reaction terminates, concentration of reaction solution, obtains white powdery solids, washed with dichloromethane 3 times, suction filtration, and vacuum-drying, obtains white powdery solids, and be intermediate III a-g, reaction equation is as follows:
D: under nitrogen protection, intermediate III and diacetyl oxide 5-10 hour, after reaction terminates, poured in frozen water by reaction solution and stir 1-3 hour, suction filtration obtains crude product, and crude product uses water, washing with alcohol successively.EtOH-CHCl 3recrystallization, dry, compound in triazine class IV a-g of get Han oxazoline ring, reaction equation is as follows:
Beneficial effect of the present invention is as follows:
(1) compound in triazine class of Han oxazoline ring provided by the invention, simple to operate, and technique is advanced, solvent recoverable;
(2) oxazoline ring structure unit is incorporated in triaizine compounds by the compound in triazine class Shi with antitumour activity Han oxazoline ring provided by the invention, reach the object of antitumour activity, to the growth in vitro of liver cancer cell (HepG-2), lung carcinoma cell (A549-1) cell and breast cancer cell (231-2) three kinds of JEG-3, there is stronger inhibit activities.
Embodiment
Below in conjunction with embodiment, the invention will be further described, but the scope of protection of present invention is not limited to the scope of embodiment statement.
With trichlorine paracyanogen for raw material, intermediate I is obtained with phenol reactant, intermediate I again with p-Hydroxybenzaldehyde Reactive Synthesis intermediate II, then intermediate II and fragrant hydrazides react and generate intermediate III a-g, and last intermediate III Chengs triaizine compounds IV a-g of Han oxazoline with diacetyl oxide effect cyclodehydration.
The core texture fragment of oxazoline, triazine is rationally assembled and modifies, and synthesizes the compound in triazine class with antitumour activity Han oxazoline ring.
Embodiment 1:
Have the compound in triazine class of antitumour activity Han oxazoline ring, step is:
The synthesis of intermediate I
In the mixing solutions of acetone-water (volume ratio is 1:1), add phenol (0.2mol, 19.76g), sodium hydroxide (0.2mol, 8.4g), cyanuric chloride (0.1mol, 18.45g), after 8 hours, after reaction terminates, reaction solution is poured in frozen water 10-30 DEG C of reaction at control temperature, stir 10min, suction filtration, filter cake deionized water drip washing 3-4 time, 50 DEG C of vacuum-dryings, obtain white powdery solids, intermediate I, yield 93.2%..
The synthesis of intermediate II
Under nitrogen protection; be equipped with in the flask of thermometer, constant pressure funnel, reflux condensing tube and drying tube and first add Carbon Dioxide caesium (0.015mol; 4.89g), 4-hydroxy benzaldehyde (0.015mol; 1.83g); 30mLN; after dinethylformamide reaction 2h; add intermediate I (0.01mol, 3.0g), stirring at room temperature 20-24h; after reaction terminates; reaction solution is poured in deionized water, stir, suction filtration; filter cake deionized water wash 3-4 time, is placed in vacuum drying oven dry.Obtain white powdery solids, reaction intermediate II, yield 90.1%.
The synthesis of intermediate III-a
Under nitrogen protection, in organic mixed solvent, add intermediate II (0.01mol, 3.85g), benzoyl hydrazine (0.015mol, 2.04g), react 10 hours.After reaction terminates, concentration of reaction solution, obtains white powdery solids, washed with dichloromethane 3 times, suction filtration, and vacuum-drying, obtains white powdery solids, is compound intermediate III-a, white powder, yield 88.6%.
The synthesis of intermediate IV-a
In reaction flask, add 0.01mol (5.03g) intermediate III-a, diacetyl oxide 0.06mol (6.12g), backflow 8h, be cooled to room temperature, stir 1h in the frozen water poured into by reaction solution, suction filtration obtains crude product, and crude product uses water, washing with alcohol successively.EtOH-CHCl 3recrystallization, dry, the triaizine compounds IV-a of get Han oxazoline.White powder, yield 81.2%, IRR (KBr, cm-1): 3042,1716,1631,1604,1581,1231,1081. 1hNMR (CDCl 3, 400MHz): 7.91-7.86 (m, 4H, Ar-H), (7.56-7.58 m, 5H, Ar-H), (7.32-7.27 m, 5H, Ar-H), (7.16-7.09 m, 5H, Ar-H), (6.82 s, 1H, Oxadiazoline-H), 2.05 (s, 3H, CH 3). 13cNMR (CDCl 3, 100MHz) and δ: 24.1,83.1,122.2,125.4,128.2,131.2,136.1,153.2,157.3,176.2,181.3.ESI-MS (m/z): 570.16 (M ++ Na) .Anal.CalcdForC 31h 23n 5o 5: C, 68.25H, 4.25; N, 12.84.Found:C, 68.18; H, 4.31; N, 12.78.
The chemical equation that the present invention prepares compound is:
Embodiment 2:
Intermediate I, the synthesis of intermediate II is with embodiment 1.
The synthesis of intermediate III-b
Under nitrogen protection, in organic mixed solvent, add intermediate II (0.01mol, 3.85g), 4-fluorobenzoyl hydrazine (0.015mol, 2.31g), react 8 hours.After reaction terminates, concentration of reaction solution, obtains white powdery solids, washed with dichloromethane 3 times, suction filtration, and vacuum-drying, obtains white powdery solids, is intermediate III-b, white powder, yield 81.5%.
The synthesis of intermediate VI-b
In flask, add 0.01mmol (5.21g) intermediate III-b, diacetyl oxide 0.07mmol (7.14g), backflow 7h, be cooled to room temperature, stir 1h in the frozen water poured into by reaction solution, suction filtration obtains crude product, and crude product uses water, washing with alcohol successively.EtOH-CHCl 3recrystallization, dry, the triaizine compounds IV-b of get Han oxazoline.White powder, yield 84.6%, IR (KBr, cm-1): 3052,1720,1629,1605,1493,1241,1079. 1hNMR (CDCl 3, 400MHz): 7.82-7.80 (m, 4H, Ar-H), (7.48-7.42 m, 5H, Ar-H), (7.26-7.20 m, 4H, Ar-H), (7.14-7.07 m, 4H, Ar-H), (7.02-6.87 m, 5H, Ar-H), 2.05 (s, 3H, CH 3). 13cNMR (CDCl 3, 100MHz) and δ: 23.6,84.3,119.2,122.3,127.2,133.2,137.1,155.1,158.2,173.2,182.2.ESI-MS (m/z): 586.16 (M ++ Na) .Anal.CalcdForC 31h 22n 5o 5f:C, 66.07; H, 3.94; N, 12.43.Found:C, 66.16; H, 3.87; N, 12.38.
Embodiment 3:
Intermediate I, the synthesis of intermediate II is with embodiment 1.
The synthesis of intermediate III-c
Under nitrogen protection, in organic mixed solvent, add intermediate II (0.01mol, 3.85g), 4-chlorobenzoyl hydrazine (0.015mol, 2.55g), react 8 hours.After reaction terminates, concentration of reaction solution, obtains white powdery solids, washed with dichloromethane 3 times, suction filtration, and vacuum-drying, obtains white powdery solids, is intermediate III-c, white powder, yield 80.3%.
The synthesis of intermediate VI-c
In flask, add 0.01mmol (5.37g) intermediate III-c, diacetyl oxide 0.08mmol (8.16g), backflow 6h, be cooled to room temperature, stir 1h in the frozen water poured into by reaction solution, suction filtration obtains crude product, and crude product uses water, washing with alcohol successively.EtOH-CHCl 3recrystallization, dry, the triaizine compounds IV-c of get Han oxazoline.White powder, yield 83.2%, IRIR (KBr, cm-1): 3052,1720,1629,1605,1493,1241,1079. 1hNMR (CDCl 3, 400MHz): 7.59-7.51 (m, 4H, Ar-H), (7.45-7.40 m, 4H, Ar-H), (7.39-7.32 m, 3H, Ar-H), (7.16-7.08 m, 5H, Ar-H), (7.01-6.85 m, 3H, Ar-H), 2.08 (s, 3H, CH 3). 13cNMR (CDCl 3, 100MHz) and δ: 23.1,82.5,120.2,123.1,126.2,134.2,136.5,159.1,161.2,173.5,181.9.ESI-MS (m/z): 602.13 (M ++ Na) .Anal.CalcdForC 31h 22n 5o 5cl:C, 64.20; H, 3.82; N, 12.08.Found:C, 64.12; H, 3.94; N, 12.01.
Embodiment 4:
Intermediate I, the synthesis of intermediate II is with embodiment 1.
The synthesis of intermediate III-d
Under nitrogen protection, in organic mixed solvent, add intermediate II (0.01mol, 3.85g), 3-chlorobenzoyl hydrazine (0.015mol, 2.55g), react 8 hours.After reaction terminates, concentration of reaction solution, obtains white powdery solids, washed with dichloromethane 3 times, suction filtration, and vacuum-drying, obtains white powdery solids, is intermediate III-d, white powder, yield 83.6%.
The synthesis of intermediate IV-d
In flask, add 0.01mmol (5.37g) intermediate III-d, diacetyl oxide 0.09mmol (9.18g), backflow 6h, be cooled to room temperature, stir 1h in the frozen water poured into by reaction solution, suction filtration obtains crude product, and crude product uses water, washing with alcohol successively.EtOH-CHCl 3recrystallization, dry, the triaizine compounds IV-d of get Han oxazoline.White powder, yield 84.5%.IR (KBr, cm-1): 3051,1725,1632,1602,1453,1233,1081. 1hNMR (CDCl 3, 400MHz): 7.92-7.86 (m, 5H, Ar-H), (7.79-7.73 m, 4H, Ar-H), (7.68-7.62 m, 4H, Ar-H), (7.32-7.27 m, 3H, Ar-H), (7.05-6.83 m, 3H, Ar-H), 2.03 (s, 3H, CH 3). 13cNMR (CDCl 3, 100MHz) and δ: 22.6,84.3,121.2,124.2,128.3,135.8,137.2,156.1,160.4,174.3,180.9.ESI-MS (m/z): 602.13 (M ++ Na) .Anal.CalcdForC 31h 22n 5o 5cl:C, 64.20; H, 3.82; N, 12.08.Found:C, 64.28; H, 3.75; N, 12.14.
Embodiment 5:
Intermediate I, the synthesis of intermediate II is with embodiment 1.
The synthesis of intermediate III-e
Under nitrogen protection, in organic mixed solvent, add intermediate II (0.01mol, 3.85g), 3-nitrobenzoyl hydrazides (0.015mol, 2.72g), react 6 hours.After reaction terminates, concentration of reaction solution, obtains white powdery solids, washed with dichloromethane 3 times, suction filtration, and vacuum-drying, obtains white powdery solids, is intermediate III-e, white powder, yield 81.8%.
The synthesis of intermediate VI-e
In flask, add 0.01mmol (5.48g) intermediate III-e, diacetyl oxide 0.09mmol (9.18g), backflow 5h, be cooled to room temperature, stir 1h in the frozen water poured into by reaction solution, suction filtration obtains crude product, and crude product uses water, washing with alcohol successively.EtOH-CHCl 3recrystallization, dry, the triaizine compounds IV-e of get Han oxazoline.White powder, yield 80.3%.IR (KBr, cm-1): 3053,1716,1629,1601,1468,1241,1091. 1hNMR (CDCl 3, 400MHz): 8.48-8.41 (m, 3H, Ar-H), (8.35-8.29 m, 4H, Ar-H), (8.25-8.18 m, 4H, Ar-H), (7.31-7.25 m, 4H, Ar-H), (7.03-6.92 m, 4H, Ar-H), 2.06 (s, 3H, CH 3). 13cNMR (CDCl 3, 100MHz) and δ: 22.6,84.3,121.2,124.2,128.3,135.8,137.2,156.1,160.4,174.3,180.9.ESI-MS (m/z): 602.13 (M ++ Na) .Anal.CalcdForC 31h 22n 6o 7: C, 63.05; H, 3.76; N, 14.23.Found:C, 63.11; H, 3.82; N, 14.18.
Embodiment 6:
Intermediate I, the synthesis of intermediate II is with embodiment 1.
The synthesis of intermediate III-f
Under nitrogen protection, in organic mixed solvent, add intermediate II (0.01mol, 3.85g), 4-nitrobenzoyl hydrazides (0.015mol, 2.72g), react 6 hours.After reaction terminates, concentration of reaction solution, obtains white powdery solids, washed with dichloromethane 3 times, suction filtration, and vacuum-drying, obtains white powdery solids, is intermediate III-f, white powder, yield 86.2%.
The synthesis of IV-f
0.01mmol (5.48g) intermediate III-f is added, diacetyl oxide 0.09mmol (9.18g), backflow 5h in reaction flask, be cooled to room temperature, stir 1h in the frozen water poured into by reaction solution, suction filtration obtains crude product, and crude product uses water, washing with alcohol successively.EtOH-CHCl 3recrystallization, dry, the triaizine compounds IV-f of get Han oxazoline.White powder, yield 80.3%.IR (KBr, cm-1): 3032,1720,1632,1596,1489,1239,1086. 1hNMR (CDCl 3, 400MHz): 8.48-8.41 (m, 5H, Ar-H), (8.29-8.21 m, 3H, Ar-H), (8.24-8.17 m, 3H, Ar-H), (7.28-7.21 m, 4H, Ar-H), (7.05-6.83 m, 4H, Ar-H), 2.01 (s, 3H, CH 3). 13cNMR (CDCl 3, 100MHz) and δ: 23.2,83.1,120.8,123.2,125.7,132.4,137.3,156.6,162.3,176.3,184.5.ESI-MS (m/z): 602.13 (M ++ Na) .Anal.CalcdForC 31h 22n 6o 7: C, 63.05; H, 3.76; N, 14.23.Found:C, 63.01; H, 3.69; N, 14.28.
Embodiment 7:
Intermediate I, the synthesis of intermediate II is with embodiment 1.
The synthesis of intermediate III-g
Under nitrogen protection, in organic mixed solvent, add intermediate II (0.01mol, 3.85g), 4-toluyl hydrazine (0.015mol, 2.25g), react 9 hours.After reaction terminates, concentration of reaction solution, obtains white powdery solids, washed with dichloromethane 3 times, suction filtration, and vacuum-drying, obtains white powdery solids, is intermediate III-g, white powder, yield 81.2%.
The synthesis of IV-g
0.01mmol (5.17g) intermediate III-g is added, diacetyl oxide 0.09mmol (9.18g), backflow 5h in reaction flask, be cooled to room temperature, stir 1h in the frozen water poured into by reaction solution, suction filtration obtains crude product, and crude product uses water, washing with alcohol successively.EtOH-CHCl 3recrystallization, dry, the triaizine compounds IV-g of get Han oxazoline.White powder, yield 85.6%, Whitepowder, yield85.6%, M.p.112-114 DEG C of .IR (KBr, cm-1): 3062,1719,1635,1604,1542,1231,1081. 1hNMR (CDCl 3, 400MHz): 8.08-8.02 (m, 3H, Ar-H), (7.36-7.30 m, 4H, Ar-H), (7.22-7.16 m, 4H, Ar-H), (7.13-7.05 m, 3H, Ar-H), (7.02-6.81 m, 5H, Ar-H), 2.35 (s, 3H, CH 3), 2.07 (s, 3H, CH 3). 13cNMR (CDCl 3, 100MHz) and δ: 22.9,81.1,123.2,124.6,126.7,133.4,138.1,157.6,163.2,175.3,182.6.ESI-MS (m/z): 560.18 (M ++ H) .Anal.CalcdForC 32h 25n 5o 5: C, 68.69; H, 4.50; N, 12.52.Found:C, 68.61; H, 4.42; N, 12.57.
The application with the compound in triazine class of antitumour activity Han oxazoline ring provided by the invention is as follows:
To 7 new compounds synthesized as test sample, mitomycin (20ug/mL) is as positive controls.Be made into the storing solution of 1.0 × 10-2ug/mL concentration with DMSO, be diluted to desired concn with RPMI-1640 (RoswellParkMemorialInstitute).Liver cancer cell (HepG-2) cell of taking the logarithm vegetative period is inoculated in 96 orifice plates with 6000, every hole cell, cultivate overnight after, add the above-claimed cpd of different concns.Discard substratum after 48h, every hole adds the MTT solution 20uL of 5g/L, and continue cultivation and discard supernatant liquid after 4 hours, every hole adds 150uLDMSO, and vibrate 30min gently, surveys its absorbance by microplate reader at 492nm wavelength place; Lung carcinoma cell (A549-1) cell of taking the logarithm vegetative period and breast cancer cell (231-2) are inoculated in 96 orifice plates with 6000, every hole cell, cultivate overnight after, add the above-claimed cpd of different concns.Discard substratum after 48h, every hole adds the MTT solution 20uL of 5g/L, and discard supernatant liquid after continuing to cultivate 4h, every hole adds 150uLDMSO, and vibrate 30min gently, surveys its absorbance by microplate reader at 492nm wavelength place.By formulae discovery each group of inhibiting rate to cancer cells: cell inhibitory rate=(1-experimental group absorbance/control group absorbance) × 100%.Then with each drug level logarithmic value, linear regression is done to the inhibiting rate under each concentration, go out the half-inhibition concentration (IC of each test compound to experiment cancer cells from gained docs-effect Equation for Calculating 50), the results are shown in Table 1, IV b, IV c and IV f activity the strongest.
The antitumour activity of table 1 compounds Ⅳ a-IV g

Claims (10)

1., containing a compound in triazine class for oxazoline ring, it is characterized in that the compounds Ⅳ with following general structure:
In formula: Ar is any one in phenyl, 4-fluorophenyl, 4-chloro-phenyl-, 3-chloro-phenyl-, 3-nitrophenyl, 4-nitrophenyl, 4-aminomethyl phenyl;
Wherein, when Ar is phenyl, be compounds Ⅳ a; When Ar is 4-fluorophenyl, when to be compounds Ⅳ b, Ar be 4-chloro-phenyl-, to be compounds Ⅳ c, Ar be 3-chloro-phenyl-is, when to be compounds Ⅳ d, Ar be 3-nitrophenyl, when to be compounds Ⅳ e, Ar be 4-nitrophenyl, when to be compounds Ⅳ f, Ar be 4-aminomethyl phenyl, be compounds Ⅳ g.
2. prepare the method for the compound in triazine class of Han oxazoline ring according to claim 1, it is characterized in that, comprise following preparation process:
A: at acetone-water be in the mixing solutions of 1:1 with volume ratio, add phenol, sodium hydroxide, cyanuric chloride, control temperature is at 10-30 DEG C of reaction 6-10 hour, reaction terminates, and is poured into by reaction solution in frozen water, stirs 10min, suction filtration, filter cake deionized water drip washing 3-4 time, 50 DEG C of vacuum-dryings, obtain white powdery solids, be intermediate I, reaction equation is as follows:
B: under nitrogen protection, is equipped with in the flask of thermometer, constant pressure funnel, reflux condensing tube and drying tube and first adds mineral alkali, 4-hydroxy benzaldehyde and DMF; reaction 2h, adds intermediate I, stirring at room temperature 20-24h; after reaction terminates, reaction solution is poured in deionized water, stir; suction filtration; filter cake deionized water wash 3-4 time, is placed in vacuum drying oven dry, obtains white powdery solids; be intermediate II, reaction equation is as follows:
C: under nitrogen protection, in organic mixed solvent, adds intermediate II, aryl formyl hydrazine; reaction 10-15 hour; reaction terminates, and concentration of reaction solution, obtains white powdery solids; washed with dichloromethane 3 times; suction filtration, vacuum-drying, obtains white powdery solids; be intermediate III a-g, reaction equation is as follows:
D: under nitrogen protection, intermediate III and diacetyl oxide 5-10 hour, after reaction terminates, poured in frozen water by reaction solution and stir 1-3 hour, suction filtration obtains crude product, and crude product uses water, washing with alcohol successively, EtOH-CHCl 3recrystallization, dry, the compound in triazine class IV of get Han oxazoline ring, reaction equation is as follows:
In formula: Ar is any one in phenyl, 4-fluorophenyl, 4-chloro-phenyl-, 3-chloro-phenyl-, 3-nitrophenyl, 4-nitrophenyl, 4-aminomethyl phenyl;
Wherein, when Ar is phenyl, be compounds Ⅳ a; When Ar is 4-fluorophenyl, when to be compounds Ⅳ b, Ar be 4-chloro-phenyl-, to be compounds Ⅳ c, Ar be 3-chloro-phenyl-is, when to be compounds Ⅳ d, Ar be 3-nitrophenyl, when to be compounds Ⅳ e, Ar be 4-nitrophenyl, when to be compounds Ⅳ f, Ar be 4-aminomethyl phenyl, be compounds Ⅳ g.
3. the method for the compound in triazine class of preparation Han oxazoline ring according to claim 2, it is characterized in that: in steps A, the ratio of the amount of substance of cyanuric chloride, phenol is 1:2-5, the weight of acetone-water mixed solvent be cyanuric chloride, phenol gross weight 4-8 doubly.
4. the method for the compound in triazine class of preparation Han oxazoline ring according to claim 2, it is characterized in that: in step B, intermediate I is 1:2.0-1:3.0 with the ratio of 4-hydroxy benzaldehyde amount of substance.
5. the method for the compound in triazine class of preparation Han oxazoline ring according to claim 2, it is characterized in that: in step C, intermediate II is 1:2.0-2.5 with the ratio of the amount of substance of aryl hydrazide, and the weight of organic solvent is 6-10 times of intermediate II and aryl hydrazide gross weight.
6. the method for the compound in triazine class of preparation Han oxazoline ring according to claim 2, it is characterized in that: in step D, intermediate III a-g is 1:5.0-9.0 with the ratio of the amount of substance of diacetyl oxide.
7. the method for the compound in triazine class of preparation Han oxazoline ring according to claim 2, is characterized in that: mineral alkali described in step B is any one in cesium carbonate, sodium carbonate, salt of wormwood, and preferred mineral alkali is cesium carbonate.
8. the method for the compound in triazine class of preparation Han oxazoline ring according to claim 2, it is characterized in that: the organic mixed solvent described in step C is dehydrated alcohol and tetrahydrofuran (THF) or methyl-sulphoxide or N, dinethylformamide take volume ratio as the mixed solvent of 1:1, is preferably the mixed solvent that dehydrated alcohol-tetrahydrofuran (THF) take volume ratio as 1:1.
9. the application of compound in triazine class on preparation treatment cancer therapy drug of Han oxazoline ring described in any one of claim 1-8.
10. the compound in triazine class of Han oxazoline ring according to claim 9 treats the application on the medicine of anti-liver cancer cell (HepG-2), lung carcinoma cell (A549-1) cell or breast cancer cell (231-2) in preparation.
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CN106946858A (en) * 2017-04-15 2017-07-14 三峡大学 A kind of melamine class compound and preparation method thereof
EP3858909A4 (en) * 2018-09-26 2022-06-15 Adeka Corporation Nucleating agent, synthetic-resin composition containing same, and molded object thereof

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CN102573485A (en) * 2009-06-08 2012-07-11 加利福尼亚资本权益有限责任公司 Triazine derivatives and their therapeutical applications

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CN102573485A (en) * 2009-06-08 2012-07-11 加利福尼亚资本权益有限责任公司 Triazine derivatives and their therapeutical applications

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106946858A (en) * 2017-04-15 2017-07-14 三峡大学 A kind of melamine class compound and preparation method thereof
EP3858909A4 (en) * 2018-09-26 2022-06-15 Adeka Corporation Nucleating agent, synthetic-resin composition containing same, and molded object thereof

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