CN106397445A - Pyrazoles N-p-bromophenyl maleimide derivative containing chromone structure as well as preparation method and application thereof - Google Patents
Pyrazoles N-p-bromophenyl maleimide derivative containing chromone structure as well as preparation method and application thereof Download PDFInfo
- Publication number
- CN106397445A CN106397445A CN201610279322.3A CN201610279322A CN106397445A CN 106397445 A CN106397445 A CN 106397445A CN 201610279322 A CN201610279322 A CN 201610279322A CN 106397445 A CN106397445 A CN 106397445A
- Authority
- CN
- China
- Prior art keywords
- chromone
- bromophenyl
- bromo
- pyrazoles
- diketone
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- 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
- C07D487/04—Ortho-condensed systems
Abstract
The invention discloses 3-(6-bromo-4-oxy-4H-chromone)-1-phenyl-5-p-bromophenyl-1,6a-dihydrogen pyrroline[3,4-c]pyrazole-4,6(3aH,5H)-diketone as well as a preparation method and application thereof. According to the preparation method, a chromone structure is introduced into N-p-bromophenyl maleimide on the basis of introducing a pentabasic pyrazolone ring by using a 1,3-dipolar cycloaddition method, so that novel 3-(6-bromo-4-oxy-4H-chromone)-1-phenyl-5-p-bromophenyl-1,6a-dihydrogen pyrroline[3,4-c]pyrazole-4,6(3aH,5H)-diketone is synthesized. The abovecompound has a good inhibitory action on tumor cell lines, has a better inhibition rate and selectivity for leukemia cells, and has a very good industrial application prospect in aspects of preparation of antitumor drugs, and the like.
Description
Technical field：
The present invention relates to a kind of new pyrazoles N p-bromophenyl maleimide derivatives containing chromone structure, specifically
Refer to 3- (6- bromo- 4- oxygen -4H- chromone) -1- phenyl -5- p-bromophenyl -1,6a- pyrrolin quinoline [3,4-c] pyrazoles -4,6
(3aH, 5H)-diketone and preparation method and application.
Background technology：
N- p-bromophenyl maleimide, chemical name：1- p-bromophenyl pyrrolidines -2,5- diketone, chemical structural formula is as follows：
1- p-bromophenyl 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 more active class reaction in heterocyclic drug chemical research.In recent years, because chromone is extensive
Biologically active, anticancer, antibacterial, suppression platelet aggregation etc. and receive much attention.So, either from pharmacology still from conjunction
Angled consideration, this heterocyclic compounds has very high synthesis to be worth.
Pyrazole derivatives are 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 molecule by the different heterocycles of research and to produced by pharmacologically active
Impact, thus provide a kind of brand-new pyrazoles N p-bromophenyl maleimide derivatives containing chromone structure.
Content of the invention：
A first aspect of the present invention purpose is to provide a kind of new pyrazoles N p-bromophenyl Malaysia containing chromone structure
Imide derivative.
The technical scheme that the present invention takes is as follows：
A kind of pyrazoles N p-bromophenyl maleimide derivatives containing chromone structure, its chemical name is：3-(6-
Bromo- 4- oxygen -4H- chromone) -1- phenyl -5- p-bromophenyl -1,6a- pyrrolin quinoline [3,4-c] pyrazoles -4,6 (3aH, 5H)-two
Ketone, its structural formula is as follows：
This compound relevant experimental data is as follows：
Applicant is found by research：Replaced in the structure of pyrazoles using chromone derivative, to N- p-bromophenyl
Maleimide carries out structure of modification, obtains a kind of brand-new pyrazoles N p-bromophenyl maleimide containing chromone structure
Amine 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-bromophenyl Malaysia containing chromone structure
The preparation method of imide derivative is it is characterised in that comprise the following steps：Maleic anhydride and para-bromoaniline reaction are closed
Become N- p-bromophenyl maleimide (3), then adopt 6- bromo chromone to synthesize 6- bromo chromone phenylhydrazone with phenylhydrazine dehydration
(4), finally N- p-bromophenyl maleimide (3) and 6- bromo chromone phenylhydrazone (4) is carried out Dipolar Cycloaddition, synthesize 3-
(6- bromo- 4- oxygen -4H- chromone) -1- phenyl -5- p-bromophenyl -1,6a- pyrrolin quinoline [3,4-c] pyrazoles -4,6 (3aH, 5H) -
Diketone (5).
Reaction equation according to the present invention is as follows：
Further, described a kind of 3- (6- bromo- 4- oxygen -4H- chromone) -1- phenyl -5- p-bromophenyl -1,6a- dihydro
Pyrrolin [3,4-c] pyrazoles -4, the preparation method of 6 (3aH, 5H)-diketone is it is characterised in that comprise the following steps：
(1), the synthesis of N- p-bromophenyl maleimide：
Maleic anhydride and para-bromoaniline are dissolved in acetone solvent, react under agitation and progressively produce faint yellow
Precipitation, room temperature reaction, after 1 hour, takes a small amount of precipitation, through washing, is dried, sequentially adds manganese acetate, triethylamine and aceticanhydride, heats up
Afterwards, precipitation progressively dissolves, and reacts 2 hours at 50～60 DEG C, and solution becomes red-black by orange, engenders new precipitation, cold
But to room temperature, precipitate through washing in water, be dried, obtain product N- p-bromophenyl 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 adopts 6- bromine
The method generating schiff bases with phenylhydrazine dehydration for chromone is synthesized：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 anhydrous dissolved with 2mmol 6- bromo chromone into 20mL
Ethanol solution, continues boiling water bath return stirring 1h, drips 10 hydrochloric acid, has pale yellow precipitate to occur；Continuous boiling water bath backflow is stirred
Mix 5h, stop water-bath, plus people's 20mL distilled water stirs, pale yellow precipitate darkens, and suction filtration obtains 6- bromo chromone phenylhydrazone, for Huang
Red needle-like product, is rinsed 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-bromophenyl 1,6a pyrrolin quinoline [3,4 c] pyrrole
The synthesis of azoles 4,6 (3aH, 5H) diketone：
By 1mmol N- p-bromophenyl maleimide (3) and 1.1mmol 6- bromo chromone phenylhydrazone (4) in 20mL ethanol
In, add 1.2mL toluene-sodium-sulfonchloramide, flow back 12 hours, precipitation is filtered, cleaning, with methyl alcohol recrystallization, produced after vacuum drying
Thing 3 (6 bromine 4 oxygen 4H chromone) 1 phenyl 5 p-bromophenyl 1,6a pyrrolin quinoline [3,4 c] pyrazoles 4,6 (3aH,
5H) diketone (5).
Further it is provided in：
In described step (1), react the pale yellow precipitate obtaining and 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 to bromobenzene
Application in terms of preparing antineoplastic for 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 strains for example human liver cancer cell, cancer cell of oral cavity, stomach cancer cell, ovarian cancer cell,
Leukaemia, colon-cancer cell etc., are respectively provided with inhibitory action, wherein have more preferably inhibiting rate and selection for leukaemia
Property, antineoplastic can be manufactured separately, anti-tumor compositions can also be prepared as active component and other antineoplastics, tool
There is extraordinary prospects for commercial application.
Beneficial effects of the present invention are as follows：
The applicant it has been investigated that, replaced in the structure of pyrazoles using chromone derivative, to N- p-bromophenyl
Maleimide carries out structure of modification, obtains a kind of brand-new pyrazoles N p-bromophenyl maleimide containing chromone structure
Amine derivative, this compound can change pharmacologically active, and through further experiment and analysis, the different heterocycle of research is in same molecule
Middle gathering and on affecting produced by pharmacologically active, applicant synthesized the pyrrole containing chromone structure by Dipolar Cycloaddition
Azole N p-bromophenyl maleimide derivatives, the new pyrazoles N p-bromophenyl containing chromone structure of the method preparation
Maleimide derivatives, in terms of preparing antineoplastic, have extraordinary prospects for commercial application.
Specific embodiment：
With reference to embodiments 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-bromophenyl maleimide：
Maleic anhydride and para-bromoaniline are dissolved in a certain amount of acetone solvent, under agitation that para-bromoaniline is molten
Drop adds to the reaction bulb containing maleic acid anhydride solution, and exothermic heat of reaction simultaneously progressively produces pale yellow precipitate, and room temperature reaction 1 is little
Shi Hou, takes a small amount of precipitation, through washing, is dried, sequentially adds manganese acetate, triethylamine and aceticanhydride, and after intensification, precipitation progressively dissolves,
React 2 hours at 50～60 DEG C, solution becomes red-black by orange, engenders new precipitation, is cooled to room temperature, precipitates in water
Through massive laundering, drying, obtain product N- p-bromophenyl 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, boiling water bath return stirring to dissolving, Ran Houhuan
Slowly it is added dropwise to the ethanol solution dissolved with 2mmol 6- bromo chromone for the 20mL, continues boiling water bath return stirring 1h, drip 10
Hydrochloric acid, has pale yellow precipitate to occur.Continuous boiling water bath return stirring 5h, stops water-bath, plus the stirring of people's 20mL distilled water, faint yellow
Precipitation darkens, and suction filtration obtains phenylhydrazone, yellowish red color needle-like product.Rinsed 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-bromophenyl 1,6a pyrrolin quinoline [3,4
C] pyrazoles 4,6 (3aH, 5H) diketone synthesis：
By 1mmol N- p-bromophenyl maleimide and 1.1mmol 6- bromo chromone phenylhydrazone (4) in 20mL ethanol,
Add 1.2mL toluene-sodium-sulfonchloramide, flow back 12 hours.Precipitation is filtered, cleaning, with methyl alcohol recrystallization, after vacuum drying, obtain product 3
(6 bromine 4 oxygen 4H chromone) 1 phenyl 5 p-bromophenyl 1,6a pyrrolin quinoline [3,4 c] pyrazoles 4,6 (3aH, 5H)
Diketone (5).Product is yellow crystal, yield 74.6%, 189 DEG C of m.p.187.5.
Compound (5) structural confirmation：C26H15Br2N3O4
1H NMR(DMSO)δ:7.234 7.493 (m, 12H, Ar H), 6.47 (s, 1H, C=C H), 5.82 (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:592.94 (100.0%), 590.94 (51.3%), 594.94 (48.9%).
Anal.calcd.for C26H15Br2N3O4：C,52.66；H,2.58；N,7.08.
Application Example 4：Using mtt assay detect test-compound (5) to different knurl strains antitumor activity.
Compound (5) prepared by above-described embodiment, with different knurl strains, [(human 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 adopts
Tetramethyl azo azoles salt micro enzyme reaction colorimetric method (mtt assay), activity half-inhibition concentration represents (IC50).
Specific experiment step is as follows：
By compound 5 with DMSO dissolve, dilution, tumour cell Bel-7402 (human liver cancer cell), KB (cancer cell of oral cavity),
SGC7901 (stomach cancer cell), HO8901 (ovarian cancer cell), HL-60 (leukaemia), ECA109 (colon-cancer cell) are in 96 holes
Plant into 4000/200 μ L/ holes on plate, every hole adds compound 2 μ L, final concentration of 12.0 μM, 6.0 μM, 3.0 μM, 1.5 μM, common
It is same as 37 DEG C, 5%CO2It is incubated 72 hours in cell culture incubator, with DMSO (1%) as blank.After 72 hours, add dense eventually
Spend the MTT for 0.25mg/mL, be placed in 37 DEG C, 5%CO24 hours in cell culture incubator, blot solvent afterwards, every hole adds 100 μ
L DMSO, with enzyme linked immunological instrument at 570nm mensuration absorbance (OD value), the data obtained is used for calculating IC50Value.Select suppression to live
Property high compound, measure the compound effects time different impact to human tumor cells cycle and apoptosis under variable concentrations.
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 IC to six kinds of tumor cell lines for the pyrazoles N- p-bromophenyl maleimide derivatives50Value
Be can be seen that by upper table data：The compound of present invention preparation, is respectively provided with suppression for six kinds of tumor cell lines
Effect, wherein has more preferable inhibiting rate and selectivity for HL-60 (leukaemia), antineoplastic can be manufactured separately
Thing, anti-tumor compositions can also be prepared as active component and other antineoplastics, before there is extraordinary commercial Application
Scape.
Claims (5)
1.3- (6- bromo- 4- oxygen -4H- chromone) -1- phenyl -5- p-bromophenyl -1,6a- pyrrolin quinoline [3,4-c] pyrazoles -4,6
(3aH, 5H)-diketone, its structural formula is as follows：
2. a kind of 3- (6- bromo- 4- oxygen -4H- chromone) -1- phenyl -5- p-bromophenyl -1,6a- pyrrolin quinoline [3,4-c] pyrazoles -
The preparation method of 4,6 (3aH, 5H)-diketone is it is characterised in that comprise the following steps：Will be anti-to maleic anhydride and para-bromoaniline
N- p-bromophenyl maleimide should be synthesized, then adopt 6- bromo chromone to synthesize 6- bromo chromone benzene with phenylhydrazine dehydration
N- p-bromophenyl maleimide and 6- bromo chromone phenylhydrazone are finally carried out Dipolar Cycloaddition, (6- is bromo- for synthesis 3- by hydrazone
4- oxygen -4H- chromone) -1- phenyl -5- p-bromophenyl -1,6a- pyrrolin quinoline [3,4-c] pyrazoles -4,6 (3aH, 5H)-diketone.
3. a kind of 3- (6- bromo- 4- oxygen -4H- chromone) -1- phenyl -5- p-bromophenyl -1,6a- two according to claim 2
Hydrogen pyrrolin [3,4-c] pyrazoles -4, the preparation method of 6 (3aH, 5H)-diketone is it is characterised in that comprise the following steps：
(1), the synthesis of N- p-bromophenyl maleimide：
Maleic anhydride and para-bromoaniline are dissolved in acetone solvent, it is faint yellow heavy to react under agitation and progressively produce
Form sediment, room temperature reaction, after 1 hour, takes a small amount of precipitation, through washing, is dried, sequentially adds manganese acetate, triethylamine and aceticanhydride, after intensification,
Precipitation progressively dissolves, and reacts 2 hours at 50～60 DEG C, and solution becomes red-black by orange, engenders new precipitation, is cooled to
Room temperature, precipitates through washing, is dried, obtain product N- p-bromophenyl 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, then slowly drips
Add 20mL dissolved with the ethanol solution of 2mmol 6- bromo chromone, continue boiling water bath return stirring 1h, drip 10 hydrochloric acid,
Pale yellow precipitate is had to occur；Continuous boiling water bath return stirring 5h, stops water-bath, plus the stirring of people's 20mL distilled water, pale yellow precipitate
Darken, suction filtration obtains 6- bromo chromone phenylhydrazone, be yellowish red color needle-like product, rinsed repeatedly with absolute ether, be vacuum dried
Product；
(3), 3 (6 bromine 4 oxygen 4H chromone) 1 phenyl 5 p-bromophenyl 1,6a pyrrolin quinoline [3,4 c] pyrazoles 4,
The synthesis of 6 (3aH, 5H) diketone:
By 1mmol N- p-bromophenyl maleimide and 1.1mmol 6- bromo chromone phenylhydrazone in 20mL ethanol, add
1.2mL toluene-sodium-sulfonchloramide, flows back 12 hours, and precipitation is filtered, cleaning, with methyl alcohol recrystallization, obtains product 3 (6 bromines after vacuum drying
4 oxygen 4H chromones) 1 phenyl 5 p-bromophenyl 1,6a pyrrolin quinoline [3,4 c] pyrazoles 4,6 (3aH, 5H) diketone.
4. a kind of 3- (6- bromo- 4- oxygen -4H- chromone) -1- phenyl -5- p-bromophenyl -1,6a- two according to claim 3
Hydrogen pyrrolin [3,4-c] pyrazoles -4, the preparation method of 6 (3aH, 5H)-diketone it is characterised in that：In described step (1), instead
The pale yellow precipitate that should obtain need to carry out filtration under diminished pressure.
5. application in terms of preparing antineoplastic for the compound described in a kind of claim 1.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610279322.3A CN106397445B (en) | 2016-04-29 | 2016-04-29 | Pyrazoles N- p-bromophenyl maleimide derivatives containing chromone structure and preparation method and application |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610279322.3A CN106397445B (en) | 2016-04-29 | 2016-04-29 | Pyrazoles N- p-bromophenyl maleimide derivatives containing chromone structure and preparation method and application |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN106397445A true CN106397445A (en) | 2017-02-15 |
| CN106397445B CN106397445B (en) | 2018-05-29 |
Family
ID=58005515
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610279322.3A Active CN106397445B (en) | 2016-04-29 | 2016-04-29 | Pyrazoles N- p-bromophenyl maleimide derivatives containing chromone structure and preparation method and application |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106397445B (en) |
Cited By (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108623603A (en) * | 2018-06-20 | 2018-10-09 | 绍兴文理学院元培学院 | A kind of L-Leu substituted maleimide amine derivative and the preparation method and application thereof |
| CN108623604A (en) * | 2018-06-20 | 2018-10-09 | 绍兴文理学院元培学院 | A kind of D-phenylalanine substituted maleimide amine derivative and the preparation method and application thereof |
| CN108676008A (en) * | 2018-06-20 | 2018-10-19 | 绍兴文理学院元培学院 | A kind of D-Leu substituted maleimide amine derivative and the preparation method and application thereof |
| CN108690028A (en) * | 2018-06-20 | 2018-10-23 | 绍兴文理学院元培学院 | A kind of Valine substituted maleimide amine derivative and the preparation method and application thereof |
| CN108707153A (en) * | 2018-06-20 | 2018-10-26 | 绍兴文理学院元培学院 | A kind of D-Val substituted maleimide amine derivative and the preparation method and application thereof |
| CN108727383A (en) * | 2018-06-20 | 2018-11-02 | 绍兴文理学院元培学院 | A kind of L-phenylalanine substituted maleimide amine derivative and the preparation method and application thereof |
| CN109988178A (en) * | 2019-04-30 | 2019-07-09 | 绍兴文理学院元培学院 | The p-nitrophenyl substituted maleimide amine of N- containing pyrrazole structure α-terpinene cycloaddition derivative and its preparation method and application |
| CN109988176A (en) * | 2019-04-30 | 2019-07-09 | 绍兴文理学院元培学院 | The p-bromophenyl substituted maleimide amine of N- containing pyrrazole structure α-terpinene cycloaddition derivative and its preparation method and application |
| CN109988179A (en) * | 2019-04-30 | 2019-07-09 | 绍兴文理学院元培学院 | The phenyl substituted maleimide amine of N- containing pyrrazole structure α-terpinene cycloaddition derivative and its preparation method and application |
| CN109988177A (en) * | 2019-04-30 | 2019-07-09 | 绍兴文理学院元培学院 | The p-methoxyphenyl substituted maleimide amine of N- containing pyrrazole structure α-terpinene cycloaddition derivative and its preparation method and application |
| CN110003224A (en) * | 2019-04-30 | 2019-07-12 | 绍兴文理学院元培学院 | The p-methylphenyl substituted maleimide amine of N- containing pyrrazole structure α-terpinene cycloaddition derivative and its preparation method and application |
| CN110105364A (en) * | 2019-04-30 | 2019-08-09 | 绍兴文理学院元培学院 | The rubigan substituted maleimide amine of N- containing pyrrazole structure α-terpinene cycloaddition derivative and its preparation method and application |
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 CN201610279322.3A patent/CN106397445B/en active Active
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》 * |
Cited By (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108623604B (en) * | 2018-06-20 | 2020-05-19 | 绍兴文理学院元培学院 | D-phenylalanine substituted maleimide derivative and preparation method and application thereof |
| CN108623603B (en) * | 2018-06-20 | 2020-05-19 | 绍兴文理学院元培学院 | L-leucine substituted maleimide derivative and preparation method and application thereof |
| CN108690028B (en) * | 2018-06-20 | 2020-05-19 | 绍兴文理学院元培学院 | L-valine substituted maleimide derivative and preparation method and application thereof |
| CN108727383B (en) * | 2018-06-20 | 2020-05-19 | 绍兴文理学院元培学院 | L-phenylalanine substituted maleimide derivative and preparation method and application thereof |
| CN108623604A (en) * | 2018-06-20 | 2018-10-09 | 绍兴文理学院元培学院 | A kind of D-phenylalanine substituted maleimide amine derivative and the preparation method and application thereof |
| CN108727383A (en) * | 2018-06-20 | 2018-11-02 | 绍兴文理学院元培学院 | A kind of L-phenylalanine substituted maleimide amine derivative and the preparation method and application thereof |
| CN108623603A (en) * | 2018-06-20 | 2018-10-09 | 绍兴文理学院元培学院 | A kind of L-Leu substituted maleimide amine derivative and the preparation method and application thereof |
| CN108707153B (en) * | 2018-06-20 | 2020-05-19 | 绍兴文理学院元培学院 | D-valine substituted maleimide derivative and preparation method and application thereof |
| CN108676008B (en) * | 2018-06-20 | 2020-05-19 | 绍兴文理学院元培学院 | D-leucine substituted maleimide derivative and preparation method and application thereof |
| CN108690028A (en) * | 2018-06-20 | 2018-10-23 | 绍兴文理学院元培学院 | A kind of Valine substituted maleimide amine derivative and the preparation method and application thereof |
| CN108676008A (en) * | 2018-06-20 | 2018-10-19 | 绍兴文理学院元培学院 | A kind of D-Leu substituted maleimide amine derivative and the preparation method and application thereof |
| CN108707153A (en) * | 2018-06-20 | 2018-10-26 | 绍兴文理学院元培学院 | A kind of D-Val substituted maleimide amine derivative and the preparation method and application thereof |
| CN109988177A (en) * | 2019-04-30 | 2019-07-09 | 绍兴文理学院元培学院 | The p-methoxyphenyl substituted maleimide amine of N- containing pyrrazole structure α-terpinene cycloaddition derivative and its preparation method and application |
| CN109988179A (en) * | 2019-04-30 | 2019-07-09 | 绍兴文理学院元培学院 | The phenyl substituted maleimide amine of N- containing pyrrazole structure α-terpinene cycloaddition derivative and its preparation method and application |
| CN109988176A (en) * | 2019-04-30 | 2019-07-09 | 绍兴文理学院元培学院 | The p-bromophenyl substituted maleimide amine of N- containing pyrrazole structure α-terpinene cycloaddition derivative and its preparation method and application |
| CN109988178A (en) * | 2019-04-30 | 2019-07-09 | 绍兴文理学院元培学院 | The p-nitrophenyl substituted maleimide amine of N- containing pyrrazole structure α-terpinene cycloaddition derivative and its preparation method and application |
| CN110105364A (en) * | 2019-04-30 | 2019-08-09 | 绍兴文理学院元培学院 | The rubigan substituted maleimide amine of N- containing pyrrazole structure α-terpinene cycloaddition derivative and its preparation method and application |
| CN110003224A (en) * | 2019-04-30 | 2019-07-12 | 绍兴文理学院元培学院 | The p-methylphenyl substituted maleimide amine of N- containing pyrrazole structure α-terpinene cycloaddition derivative and its preparation method and application |
| CN109988177B (en) * | 2019-04-30 | 2021-08-24 | 绍兴文理学院元培学院 | Pyrazole structure-containing N-p-methoxyphenyl substituted maleimide alpha-terpinene cycloaddition derivative and preparation method and application thereof |
| CN109988178B (en) * | 2019-04-30 | 2021-08-24 | 绍兴文理学院元培学院 | Pyrazole structure-containing N-p-nitrophenyl substituted maleimide alpha-terpinene cycloaddition derivative and preparation method and application thereof |
| CN110105364B (en) * | 2019-04-30 | 2021-08-24 | 绍兴文理学院元培学院 | Pyrazole structure-containing N-p-chlorophenyl substituted maleimide alpha-terpinene cycloaddition derivative, and preparation method and application thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN106397445B (en) | 2018-05-29 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN106397445A (en) | Pyrazoles N-p-bromophenyl maleimide derivative containing chromone structure as well as preparation method and application thereof | |
| CN107674083B (en) | A kind of preparation method and applications of the L-Leu ring substituent norcantharidin derivative of the structure containing pyridazinone | |
| CN106220642B (en) | A kind of L-Leu ring substituent norcantharidin derivative and the preparation method and application thereof | |
| CN106083873B (en) | A kind of L-phenylalanine ring substituent norcantharidin derivative and the preparation method and application thereof | |
| CN106188080B (en) | A kind of D-phenylalanine ring substituent norcantharidin derivative and the preparation method and application thereof | |
| CN106083884B (en) | A kind of D-Leu ring substituent norcantharidin derivative and the preparation method and application thereof | |
| CN105906633B (en) | Pyrazoles N phenyl maleimide derivatives containing chromone structure and preparation method and application | |
| CN106046019B (en) | A kind of Valine ring substituent norcantharidin derivative and the preparation method and application thereof | |
| CN106188081B (en) | A kind of D-Val ring substituent norcantharidin derivative and the preparation method and application thereof | |
| CN105859724B (en) | Rubigan 1,6a pyrrolin quinoline [3,4 c] pyrazoles 4,6 (3aH, 5H) diketone of 3 (the oxygen 4H chromones of 6 bromine 4) 1 phenyl 5 and preparation method and application | |
| CN105924445B (en) | Pyrazoles N- p-nitrophenyl maleimide derivatives containing chromone structure and preparation method and application | |
| CN105906632B (en) | Pyrazoles N- p-methylphenyl maleimide derivatives containing chromone structure and preparation method and application | |
| CN105906634B (en) | P-methoxyphenyl 1,6a pyrrolin quinoline [3,4 c] pyrazoles 4,6 (3aH, 5H) diketone of 3 (the oxygen 4H chromones of 6 bromine 4) 1 phenyl 5 and preparation method and application | |
| CN108164490B (en) | Genistein derivatives, their preparation and use | |
| CN109232570A (en) | A kind of spiral shell of the structure containing pyridazinone [indolizine-pyrazoline] derivative and the preparation method and application thereof | |
| CN108752364A (en) | A kind of spiral shell [- isoxazoline of indolizine] derivative and the preparation method and application thereof to methoxy substitution containing pyrrazole structure | |
| CN107674082B (en) | A kind of preparation method and applications of the D-phenylalanine ring substituent norcantharidin derivative of the structure containing pyridazinone | |
| CN107722029B (en) | A kind of preparation method and applications of the D-Leu ring substituent norcantharidin derivative of the structure containing pyridazinone | |
| CN107759611B (en) | A kind of preparation method and applications of the L-phenylalanine ring substituent norcantharidin derivative of the structure containing pyridazinone | |
| CN109988176A (en) | The p-bromophenyl substituted maleimide amine of N- containing pyrrazole structure α-terpinene cycloaddition derivative and its preparation method and application | |
| CN106083966A (en) | Fluorine replaces containing galactoside structure triazole norcantharidin derivative and preparation method and application | |
| CN106083967A (en) | Containing galactoside structure triazole norcantharidin derivative and preparation method and application | |
| CN110105364A (en) | The rubigan substituted maleimide amine of N- containing pyrrazole structure α-terpinene cycloaddition derivative and its preparation method and application | |
| CN109988178A (en) | The p-nitrophenyl substituted maleimide amine of N- containing pyrrazole structure α-terpinene cycloaddition derivative and its preparation method and application | |
| CN109988177A (en) | The p-methoxyphenyl substituted maleimide amine of N- containing pyrrazole structure α-terpinene cycloaddition derivative and its preparation method and application |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20191204 Address after: No. 99, Changli Road, Wuzhong District, Suzhou, Jiangsu 215100 Patentee after: SUZHOU CITY WUZHONG TECHNOLOGY INNOVATION PARK MANAGEMENT CO.,LTD. Address before: 312000, No. 508 West Ring Road, Yuecheng District, Zhejiang, Shaoxing Patentee before: Shaoxing University |
|
| TR01 | Transfer of patent right | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20221117 Address after: 271000 west head of peitianmen street, high tech Industrial Development Zone, Tai'an City, Shandong Province Patentee after: JEWIM PHARMACEUTICAL (SHANDONG) CO.,LTD. Address before: 215100 99 Changli Road, Wuzhong District, Suzhou City, Jiangsu Province Patentee before: SUZHOU CITY WUZHONG TECHNOLOGY INNOVATION PARK MANAGEMENT CO.,LTD. |
|
| TR01 | Transfer of patent right | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20230428 Address after: 271000 west head of peitianmen street, high tech Industrial Development Zone, Tai'an City, Shandong Province Patentee after: JEWIM PHARMACEUTICAL (SHANDONG) CO.,LTD. Patentee after: Shandong Ruishun Pharmaceutical Co.,Ltd. Address before: 271000 west head of peitianmen street, high tech Industrial Development Zone, Tai'an City, Shandong Province Patentee before: JEWIM PHARMACEUTICAL (SHANDONG) CO.,LTD. |
|
| TR01 | Transfer of patent right |