CN105924445A - Pyrazole-type N-p-nitrophenyl maleimide derivative containing chromone structure, and preparation method and application thereof - Google Patents
Pyrazole-type N-p-nitrophenyl maleimide derivative containing chromone structure, and preparation method and application thereof Download PDFInfo
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- CN105924445A CN105924445A CN201610281415.XA CN201610281415A CN105924445A CN 105924445 A CN105924445 A CN 105924445A CN 201610281415 A CN201610281415 A CN 201610281415A CN 105924445 A CN105924445 A CN 105924445A
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- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
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Abstract
The invention discloses 3-(6-bromo-4-oxo-4H-chromanone)-1-phenyl-5-p-nitrophenyl-1,6a-dihydropyrroline[3,4-c]pyrazole-4,6(3aH,5H)-dione, and a preparation method and an application thereof. According to the preparation method, a chromone structure is imported on a basis of introducing five-membered pyrazole ring into N-p-nitrophenyl maleimide with a 1,3-dipolar cycloaddition method, such that the novel 3-(6-bromo-4-oxo-4H-chromanone)-1-phenyl-5-p-nitrophenyl-1,6a-dihydropyrroline[3,4-c]pyrazole-4,6(3aH,5H)-dione is synthesized. The compound has good inhibition effect against tumor cell strains, and has better inhibition rate and selectivity upon intestinal cancer cells, human liver cancer cells, leukemia cells and the like. The derivative has an excellent industrial application prospect in the aspect of antitumor drug preparation.
Description
Technical field:
The present invention relates to a kind of new pyrazoles N p-nitrophenyl maleimide derivatives containing chromone structure, tool
Body refers to 3-(6-bromo-4-oxygen-4H-chromone)-1-phenyl-5-p-nitrophenyl-1,6a-pyrrolin quinoline [3,4-c] pyrazoles-4,
6 (3aH, 5H)-diketone and preparation method and application.
Background technology:
N-p-nitrophenyl maleimide, chemical name: 1-p-nitrophenyl pyrrolidines-2,5-diketone, chemical structural formula
As follows:
1-p-nitrophenyl pyrrolidine-2,5-dione
1,3-Dipolar Cycloaddition becomes synthesis five member ring heterocyclic compound with its good region and main selectivity
Topmost method, is also a class reaction more active in heterocyclic drug chemical research.In recent years, due to chromone widely
Biologically active, the most anticancer, antibacterial, suppression platelet aggregation etc. and receive much attention.So, either from pharmacology still from conjunction
Angled consideration, this heterocyclic compounds has the highest synthesis to be worth.
Pyrazole derivatives is as the useful intermediate of a class and multi-medicament activity out shown by themselves
Get more and more people's extensive concerning.The present invention assembled in same a part by the different heterocycle of research and to produced by pharmacologically active
Impact, thus a kind of brand-new pyrazoles N p-nitrophenyl maleimide derivatives containing chromone structure is provided.
Summary of the invention:
A first aspect of the present invention purpose is to provide a kind of new pyrazoles N p-nitrophenyl horse containing chromone structure
Carry out imide derivative.
The technical scheme that the present invention takes is as follows:
A kind of pyrazoles N p-nitrophenyl maleimide derivatives containing chromone structure, its chemical name is: 3-
(6-bromo-4-oxygen-4H-chromone)-1-phenyl-5-p-nitrophenyl-1,6a-pyrrolin quinoline [3,4-c] pyrazoles-4,6 (3aH,
5H)-diketone, its structural formula is as follows:
This compound relevant experimental data is as follows:
Applicant is found by research: use chromone derivative to replace in the structure of pyrazoles, to N-p-nitrophenyl
Base maleimide carries out structure of modification, it is thus achieved that a kind of brand-new pyrazoles N p-nitrophenyl Malaysia containing chromone structure
Imide derivative, this compound can change pharmacologically active.
A second aspect of the present invention purpose is to provide a kind of above-mentioned pyrazoles N p-nitrophenyl horse containing chromone structure
Carry out the preparation method of imide derivative, it is characterised in that comprise the following steps: by anti-to maleic anhydride and paranitroanilinum
N-p-nitrophenyl maleimide (3) should be synthesized, then use 6-bromo chromone to synthesize 6-bromo look with phenylhydrazine dehydration
Ketone phenylhydrazone (4), finally carries out dipole-diople interaction by N-p-nitrophenyl maleimide (3) and 6-bromo chromone phenylhydrazone (4) anti-
Should, synthesis 3-(6-bromo-4-oxygen-4H-chromone)-1-phenyl-5-p-nitrophenyl-1,6a-pyrrolin quinoline [3,4-c] pyrazoles-
4,6 (3aH, 5H)-diketone (5).
The reaction equation that the present invention relates to is as follows:
Further, described a kind of 3-(6-bromo-4-oxygen-4H-chromone)-1-phenyl-5-p-nitrophenyl-1,6a-bis-
Hydrogen pyrrolin [3,4-c] pyrazoles-4, the preparation method of 6 (3aH, 5H)-diketone, it is characterised in that comprise the following steps:
(1), the synthesis of N-p-nitrophenyl maleimide:
Maleic anhydride and paranitroanilinum being dissolved in acetone solvent, under agitation reaction also progressively produces yellowish
Look precipitates, and room temperature reaction, after 1 hour, takes a small amount of precipitation, through washing, is dried, is sequentially added into manganese acetate, triethylamine and aceticanhydride, rises
Wen Hou, precipitation is progressively dissolved, and reacts 2 hours at 50～60 DEG C, and solution is become red-black by orange, engenders new precipitation,
It is cooled to room temperature, water precipitates through washing, be dried, obtain product N-p-nitrophenyl maleimide (3) with acetone recrystallization
(2), the synthesis of 6-bromo chromone phenylhydrazone:
Described 6-bromo chromone phenylhydrazone (4) is known compound, and No. CAS is 68287-82-1, and the present invention uses 6-bromine
The method generating schiff bases for chromone and phenylhydrazine dehydration synthesizes: the phenylhydrazine addition taking 2mmol fills 10mL tetrahydrochysene furan
In the flask muttered, boiling water bath return stirring, to dissolving, is then slowly added dropwise into anhydrous dissolved with 2mmol 6-bromo chromone of 20mL
Ethanol solution, continues boiling water bath return stirring 1h, drips 10 hydrochloric acid, have pale yellow precipitate to occur；Boiling water bath backflow is stirred continuously
Mixing 5h, stop water-bath, add the stirring of people's 20mL distilled water, pale yellow precipitate darkens, and suction filtration obtains 6-bromo chromone phenylhydrazone, for Huang
Red needle-like product, rinses repeatedly with absolute ether, is vacuum dried to obtain product 6-bromo chromone phenylhydrazone (4)；
(3), 3 (6 bromine 4 oxygen 4H chromone) 1 phenyl 5 p-nitrophenyl 1,6a pyrrolin quinoline [3,4 c]
The synthesis of pyrazoles 4,6 (3aH, 5H) diketone:
By 1mmol N-p-nitrophenyl maleimide (3) and 1.1mmol 6-bromo chromone phenylhydrazone (4) in 20mL second
In alcohol, add 1.2mL toluene-sodium-sulfonchloramide, reflux 12 hours, precipitation is filtered, clean, use methyl alcohol recrystallization, obtain after vacuum drying
Product 3 (6 bromine 4 oxygen 4H chromone) 1 phenyl 5 p-nitrophenyl 1,6a pyrrolin quinoline [3,4 c] pyrazoles 4,6
(3aH, 5H) diketone (5).
Further it is provided in:
In described step (1), the pale yellow precipitate that reaction obtains need to carry out filtration under diminished pressure.
A third aspect of the present invention purpose is to provide a kind of 3 (6 bromine 4 oxygen 4H chromone) 1 phenyl 5 p-nitrophenyl
The application in terms of preparing antineoplastic of base 1,6a pyrrolin quinoline [3,4 c] pyrazoles 4,6 (3aH, the 5H) diketone.Pass through
Experimental verification: above-claimed cpd, for different knurl strain such as human liver cancer cells, cancer cell of oral cavity, stomach cancer cell, ovarian cancer cell,
Leukaemia, colon-cancer cell etc., be respectively provided with inhibitory action, wherein for ECA109 (colon-cancer cell), Bel-7402 (people's liver cancer
Cell), HL-60 (leukaemia) etc. there is more preferably inhibiting rate and selectivity, can be manufactured separately antineoplastic, can also
Prepare anti-tumor compositions as active component and other antineoplastics, there is extraordinary prospects for commercial application.
Beneficial effects of the present invention is as follows:
The applicant it has been investigated that, use chromone derivative replace in the structure of pyrazoles, to N-p-nitrophenyl
Base maleimide carries out structure of modification, it is thus achieved that a kind of brand-new pyrazoles N p-nitrophenyl Malaysia containing chromone structure
Imide derivative, this compound can change pharmacologically active, and through further experiment and analysis, the different heterocycle of research is at same point
In son assemble and on produced by pharmacologically active affect, applicant has been synthesized containing chromone structure by Dipolar Cycloaddition
Pyrazoles N p-nitrophenyl maleimide derivatives, the novel pyrazoles containing chromone structure N pair prepared by the method
Nitrobenzophenone maleimide derivatives, in terms of preparing antineoplastic, has extraordinary prospects for commercial application.
Detailed description of the invention:
Below in conjunction with embodiment, the present invention is described further, but embodiment should not be construed as the model limiting the present invention
Enclose.
Embodiment 1, the synthesis of N-p-nitrophenyl maleimide:
Maleic anhydride and paranitroanilinum are dissolved in a certain amount of acetone solvent, under agitation by p-nitrophenyl
Amine aqueous solution drops to the reaction bulb containing maleic acid anhydride solution, and exothermic heat of reaction also progressively produces pale yellow precipitate, and room temperature is anti-
After answering 1 hour, taking a small amount of precipitation, through washing, be dried, be sequentially added into manganese acetate, triethylamine and aceticanhydride, after intensification, precipitation is progressively
Dissolving, react 2 hours at 50～60 DEG C, solution is become red-black by orange, engenders new precipitation, is cooled to room temperature, water
Middle precipitation through massive laundering, be dried, obtain product N-p-nitrophenyl maleimide (3) with acetone recrystallization.
Embodiment 2, the synthesis of 6-bromo chromone phenylhydrazone:
The phenylhydrazine taking 2mmol adds in the flask filling 10mL oxolane, and boiling water bath return stirring, to dissolving, then delays
Slowly it is added dropwise to the 20mL ethanol solution dissolved with 2mmol 6-bromo chromone, continues boiling water bath return stirring 1h, drip 10
Hydrochloric acid, has pale yellow precipitate to occur.Boiling water bath return stirring 5h continuously, stops water-bath, adds the stirring of people's 20mL distilled water, faint yellow
Precipitation darkens, and suction filtration obtains phenylhydrazone, yellowish red color needle-like product.Rinse repeatedly with absolute ether, be vacuum dried to obtain product 6-bromine
For chromone phenylhydrazone (4).
Embodiment 3,3 (6 bromine 4 oxygen 4H chromone) 1 phenyl 5 p-nitrophenyl 1,6a pyrrolin quinoline [3,
4 c] synthesis of pyrazoles 4,6 (3aH, 5H) diketone:
By 1mmol N-p-nitrophenyl maleimide (3) and 1.1mmol 6-bromo chromone phenylhydrazone (4) in 20mL second
In alcohol, add 1.2mL toluene-sodium-sulfonchloramide, reflux 12 hours.Precipitation is filtered, cleans, use methyl alcohol recrystallization, obtain after vacuum drying
Product 3 (6 bromine 4 oxygen 4H chromone) 1 phenyl 5 p-nitrophenyl 1,6a pyrrolin quinoline [3,4 c] pyrazoles 4,6
(3aH, 5H) diketone (5).Product is yellow crystal, productivity 17.2%, m.p.123.5 125 DEG C.
Compound (5) structural confirmation: C26H15BrN4O6
1H NMR (DMSO) δ: 7.245-7.502 (m, 12H, Ar-H), 6.48 (s, 1H, C=C-H), 5.83 (d, J=
1010Hz, 1H), 5.34 (d, J=1014Hz, 1H),
IR 3457 (N-C=O), 3085 (ArH), 1720 (C=O), 1577 (C=N), 1296 (C-O-C) cm-1
M/e:560.02 (100.0%), 558.02 (97.3%), 559.02 (27.8%).
Anal.calcd.for C26H15BrN4O6: C, 55.83；H,2.70；N,10.02.
Application Example 4: use mtt assay detection test-compound (5) to different knurl strains antitumor activity.
The compound (5) prepared by above-described embodiment, with different knurl strains, [(people's liver cancer is thin for tumour cell Bel-7402 respectively
Born of the same parents), KB (cancer cell of oral cavity), SGC7901 (stomach cancer cell), HO8901 (ovarian cancer cell), HL-60 (leukaemia),
ECA109 (colon-cancer cell)] it is experimental subjects, test compound (5) is for the In-vitro Inhibitory Effect of different knurl strains: experiment uses
Tetramethyl azo azoles salt trace enzyme reaction colorimetric method (mtt assay), activity half-inhibition concentration represents (IC50)。
Specific experiment step is as follows:
Being dissolved by compound (5) DMSO, dilution, tumour cell Bel-7402 (human liver cancer cell), (carcinoma of mouth is thin for KB
Born of the same parents), SGC7901 (stomach cancer cell), HO8901 (ovarian cancer cell), HL-60 (leukaemia), ECA109 (colon-cancer cell) exist
Planting into 4000/200 μ L/ holes on 96 orifice plates, every hole adds compound 2 μ L, final concentration of 12.0 μMs, 6.0 μMs, 3.0 μMs, 1.5 μ
M, jointly in 37 DEG C, 5%CO2Cell culture incubator is hatched 72 hours, with DMSO (1%) as blank.After 72 hours, add
The MTT of final concentration of 0.25mg/mL, is placed in 37 DEG C, 5%CO2In cell culture incubator 4 hours, blotting solvent afterwards, every hole adds
100 μ l DMSO, measure absorbance (OD value) with enzyme linked immunological instrument at 570nm, and the data obtained is used for calculating IC50Value.Select and press down
The compound that system activity is high, the compound effects time under variable concentrations that measures is different to human tumor cells cycle and the shadow of apoptosis
Ring.
The test-compound of variable concentrations carries out scalping with 96 orifice plates, according to the inhibiting rate of gained, calculates IC50Value, result
See table.
Table 1, the pyrazoles N p-nitrophenyl maleimide derivatives IC to six kinds of tumor cell lines50Value
By upper table data it can be seen that the compound prepared of the present invention, suppression is respectively provided with for six kinds of tumor cell lines
Effect, wherein has more for ECA109 (colon-cancer cell), Bel-7402 (human liver cancer cell), HL-60 (leukaemia) etc.
Good inhibiting rate and selectivity, can be manufactured separately antineoplastic, can also be as active component and other antineoplastics
Prepare anti-tumor compositions, there is extraordinary prospects for commercial application.
Claims (5)
1. the pyrazoles N p-nitrophenyl maleimide derivatives containing chromone structure, its chemical name is: 3-(6-
Bromo-4-oxygen-4H-chromone)-1-phenyl-5-p-nitrophenyl-1,6a-pyrrolin quinoline [3,4-c] pyrazoles-4,6 (3aH, 5H)-
Diketone, its structural formula is as follows:
2. 3-(6-bromo-4-oxygen-4H-chromone)-1-phenyl-5-p-nitrophenyl-1,6a-pyrrolin quinoline [3,4-c] pyrrole
Azoles-4, the preparation method of 6 (3aH, 5H)-diketone, it is characterised in that comprise the following steps: by maleic anhydride with to nitro
Aniline reaction synthesis N-p-nitrophenyl maleimide, then uses 6-bromo chromone to synthesize 6-bromo with phenylhydrazine dehydration
Chromone phenylhydrazone, finally carries out Dipolar Cycloaddition by N-p-nitrophenyl maleimide and 6-bromo chromone phenylhydrazone, synthesis
3-(6-bromo-4-oxygen-4H-chromone)-1-phenyl-5-p-nitrophenyl-1,6a-pyrrolin quinoline [3,4-c] pyrazoles-4,6 (3aH,
5H)-diketone.
A kind of 3-(6-bromo-4-oxygen-4H-chromone)-1-phenyl-5-p-nitrophenyl-1,6a-the most according to claim 2
Pyrrolin quinoline [3,4-c] pyrazoles-4, the preparation method of 6 (3aH, 5H)-diketone, it is characterised in that comprise the following steps:
(1), the synthesis of N-p-nitrophenyl maleimide:
Maleic anhydride and paranitroanilinum being dissolved in acetone solvent, under agitation reaction also progressively produces faint yellow sinking
Forming sediment, room temperature reaction, after 1 hour, takes a small amount of precipitation, through washing, is dried, is sequentially added into manganese acetate, triethylamine and aceticanhydride, after intensification,
Precipitation is progressively dissolved, and reacts 2 hours at 50～60 DEG C, and solution is become red-black by orange, engenders new precipitation, is cooled to
Room temperature, precipitates through washing, is dried, obtain product N-p-nitrophenyl maleimide with acetone recrystallization in water；
(2), the synthesis of 6-bromo chromone phenylhydrazone:
The phenylhydrazine taking 2mmol adds in the flask filling 10mL oxolane, and boiling water bath return stirring, to dissolving, the most slowly drips
Add the 20mL ethanol solution dissolved with 2mmol 6-bromo chromone, continue boiling water bath return stirring 1h, drip 10 hydrochloric acid,
Pale yellow precipitate is had to occur；Boiling water bath return stirring 5h continuously, stops water-bath, adds the stirring of people's 20mL distilled water, pale yellow precipitate
Darkening, suction filtration obtains 6-bromo chromone phenylhydrazone, for yellowish red color needle-like product, rinses repeatedly with absolute ether, is vacuum dried
Product；
(3), 3 (6 bromine 4 oxygen 4H chromone) 1 phenyl 5 p-nitrophenyl 1,6a pyrrolin quinoline [3,4 c] pyrazoles
The synthesis of 4,6 (3aH, 5H) diketone:
By 1mmol N-p-nitrophenyl maleimide and 1.1mmol 6-bromo chromone phenylhydrazone in 20mL ethanol, add
1.2mL toluene-sodium-sulfonchloramide, refluxes 12 hours, precipitation is filtered, and cleans, uses methyl alcohol recrystallization, obtain product 3 (6 bromines after vacuum drying
4 oxygen 4H chromones) 1 phenyl 5 p-nitrophenyl 1,6a pyrrolin quinoline [3,4 c] pyrazoles 4,6 (3aH, 5H) two
Ketone.
A kind of 3-(6-bromo-4-oxygen-4H-chromone)-1-phenyl-5-p-nitrophenyl-1,6a-the most according to claim 3
Pyrrolin quinoline [3,4-c] pyrazoles-4, the preparation method of 6 (3aH, 5H)-diketone, it is characterised in that: in described step (1),
The pale yellow precipitate that reaction obtains need to carry out filtration under diminished pressure.
5. compound application in terms of preparing antineoplastic described in a claim 1.
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Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4226776A (en) * | 1979-11-19 | 1980-10-07 | Eastman Kodak Company | Preparation of arylene-bis-maleimides |
| CN1962634A (en) * | 2006-12-01 | 2007-05-16 | 浙江大学 | Process for preparing N-phenyl maleimide |
| CN101462997A (en) * | 2008-12-30 | 2009-06-24 | 上海华谊（集团）公司 | Preparation of N-phenyl maleimide |
| CN103373949A (en) * | 2012-04-17 | 2013-10-30 | 日农科技股份有限公司 | Preparation method of N-phenylmaleimide (PMI) |
| CN103664732A (en) * | 2013-12-26 | 2014-03-26 | 上海华谊（集团）公司 | Synthetic method of N-phenylmaleimide |
| CN104892484A (en) * | 2015-06-12 | 2015-09-09 | 云南大为恒远化工有限公司 | Synthesis method for N-phenylmaleimide |
-
2016
- 2016-04-29 CN CN201610281415.XA patent/CN105924445B/en not_active Expired - Fee Related
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4226776A (en) * | 1979-11-19 | 1980-10-07 | Eastman Kodak Company | Preparation of arylene-bis-maleimides |
| CN1962634A (en) * | 2006-12-01 | 2007-05-16 | 浙江大学 | Process for preparing N-phenyl maleimide |
| CN101462997A (en) * | 2008-12-30 | 2009-06-24 | 上海华谊（集团）公司 | Preparation of N-phenyl maleimide |
| CN103373949A (en) * | 2012-04-17 | 2013-10-30 | 日农科技股份有限公司 | Preparation method of N-phenylmaleimide (PMI) |
| CN103664732A (en) * | 2013-12-26 | 2014-03-26 | 上海华谊（集团）公司 | Synthetic method of N-phenylmaleimide |
| CN104892484A (en) * | 2015-06-12 | 2015-09-09 | 云南大为恒远化工有限公司 | Synthesis method for N-phenylmaleimide |
Non-Patent Citations (4)
| Title |
|---|
| ABDOU O.ABDELHAMID ET AL.: "Reactions of hydrazonoyl halides 57: Reactions of 1-bromo-2-(5-chlorobenzofuranyl)ethanedione-1-phenylhydrazone", 《JOURNAL OF THE CHINESE CHEMICAL SOCIETY》 * |
| MICHIHIKO NOGUCHI ET AL.: "Generation of NH-azomethine imine intermediates through the 1,2-hydrogen shift of hydrazones and their intermolecular cycloaddition reaction with olefinic dipolarophiles", 《TETRAHEDRON》 * |
| 崔凯等: "N-苯基马来酰亚胺的合成", 《辽宁化工》 * |
| 解正峰等: "1,3-偶极环加成合成新型3a,6a-二氢-4,6-二氧代吡咯啉并[3,4-d]吡唑类衍生物", 《有机化学》 * |
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