CN108623638A - 12- chloro benzimidazoles -1,8- naphthalimides-platinum complex and its preparation method and application - Google Patents

12- chloro benzimidazoles -1,8- naphthalimides-platinum complex and its preparation method and application Download PDF

Info

Publication number
CN108623638A
CN108623638A CN201810729521.9A CN201810729521A CN108623638A CN 108623638 A CN108623638 A CN 108623638A CN 201810729521 A CN201810729521 A CN 201810729521A CN 108623638 A CN108623638 A CN 108623638A
Authority
CN
China
Prior art keywords
compound
preparation
formula
complex
platinum
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
Application number
CN201810729521.9A
Other languages
Chinese (zh)
Other versions
CN108623638B (en
Inventor
张业
马献力
余砚成
梁贵宾
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Dezhou Luotai Trading Co.,Ltd.
Original Assignee
Guilin Medical University
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Guilin Medical University filed Critical Guilin Medical University
Priority to CN201810729521.9A priority Critical patent/CN108623638B/en
Publication of CN108623638A publication Critical patent/CN108623638A/en
Application granted granted Critical
Publication of CN108623638B publication Critical patent/CN108623638B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07FACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F15/00Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic System
    • C07F15/0006Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic System compounds of the platinum group
    • C07F15/0086Platinum compounds
    • C07F15/0093Platinum compounds without a metal-carbon linkage
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07BGENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00Indexing scheme relating to specific properties of organic compounds
    • C07B2200/13Crystalline forms, e.g. polymorphs

Abstract

The invention discloses 1,8 naphthalimide platinum complexes of a kind of 12 chloro benzimidazole and its preparation method and application.The preparation method of the complex mainly includes the following steps that:It takes compound shown in compound and formula (III) shown in following formula (II) to be placed in organic solvent, complexation reaction is carried out under the conditions of being heated or not heated to get target product.Complex of the present invention is suitable with common antitumor drug cis-platinum to the inhibitory activity of certain cancer cells, but it is lower to people's normal cell lines of human liver 7702 toxicity of HL.Shown in the structure of complex of the present invention such as following formula (I), the structure for preparing compound shown in compound and formula (III) shown in the raw material formula (II) involved in the complex is as follows:

Description

12- chloro benzimidazoles -1,8- naphthalimides-platinum complex and preparation method thereof and Using
Technical field
The present invention relates to pharmaceutical technology fields, and in particular to a kind of 12- chloro benzimidazoles -1,8- naphthalimide-platinum cooperation Object and its preparation method and application.
Background technology
Platinum metals base anti-tumor complex is a kind of important antitumor drug library, design and the new and effective low toxicity of screening Platinum metals base anti-tumor complex is paid high attention to by Pharmaceutical Chemist.
Naphthoyl imide compounds are a kind of classical small molecule DNA intercalator, representation compound Amonafide (amonafide) and mitonafide (mitonafide) has very high active anticancer to more plants of cancer cells.But it has not yet to see There are the preparation method of 12- chloro benzimidazoles -1,8- naphthalimides-platinum complex and its relevant report to cytotoxicity.
Invention content
The technical problem to be solved in the present invention is to provide a kind of structure novel, to certain cytotoxicities height and to normal Low 12- chloro benzimidazoles -1, the 8- naphthalimide-platinum complex of hepatotoxicity and its preparation method and application.
The present invention relates to compound shown in following formula (I)s or its pharmaceutically acceptable salts:
The present invention also provides the preparation methods of above compound, mainly include the following steps that:Take following formula (II) shownization It closes compound shown in object and formula (III) in organic solvent, complexation reaction is carried out under the conditions of being heated or not heated to get target Product;
In above-mentioned preparation method, compound shown in the formula (II) is 12- chloro benzimidazole -1,8- naphthalimides, the change It closes object and can refer to existing literature (Banerji K D, Sen K K, Mazumdar A K D, Synthesis of some naphthoylenebenzimidazole,Journal of the Indian Chemical Society,197653(11), 1159-61) synthesized, also can designed, designed synthetic route synthesized.It is preferred that being synthesized using following methods:.
It stoichiometrically takes 1,8- naphthalene anhydrides and polar solvent is placed in chlorine o-phenylenediamine (4- chlorine o-phenylenediamine) and (be selected from second The combination of one or more of acid, dimethylbenzene, toluene, DMF, DMSO and ethylene glycol monomethyl ether) in back flow reaction (about 4- 8h), after reaction, cooling, there is solid precipitation, collects solid, it is dry to get to compound 12- shown in the formula (II) Chloro benzimidazole -1,8- naphthalimide (yellow crystals or powder), specific synthetic route is as follows:
In above-mentioned preparation method, compound shown in the formula (III) is that cis- dichloro two (dimethyl sulfoxide (DMSO)) closes platinum (II), existing literature (Al-Allaf T A K, et al.Transit.Met.Chem., 1998) is can refer to be prepared.
In above-mentioned preparation method, the molar ratio of compound shown in compound and formula (III) shown in the formula (II) is chemistry Ratio is measured, in actual operation, compound shown in compound or formula (III) shown in formula (II) also can be relatively excessive, but excessive Products therefrom can be caused impure.
In above-mentioned preparation method, the organic solvent can be selected from methanol, ethyl alcohol, chloroform, dichloromethane, dimethyl The combination of one or more of sulfoxide (DMSO) and n,N-Dimethylformamide (DMF).When being selected as organic solvent In above-mentioned selection when two or more mixtures, the proportioning between them can be arbitrary proportioning.The dosage of the organic solvent can It determines as needed.In specific dissolving step, compound shown in compound shown in formula (II) and formula (III) can be used respectively Organic solvent dissolves, and remixes and reacts together;Also after compound shown in compound shown in formula (II) and formula (III) being mixed It is dissolved again with organic solvent.
12- chloro benzimidazoles -1,8- naphthalimide-platinum complex of the present invention can be used molten in specific prepare It is prepared by liquid method or solvent-thermal method.
When being prepared using solwution method, include mainly:Compound shown in compound and formula (III) shown in formula (II) is taken to dissolve In organic solvent, complexation reaction being carried out under the conditions of being heated or not heated, is filtered while hot after reaction, filtrate cooling has Solid is precipitated, and collects solid, as target product.
In above-mentioned solwution method, it whether complete can react by thin-layer chromatography tracing detection.In order to improve the yield of reaction, Reaction is preferably performed under heating conditions, and is further preferably carried out under conditions of >=40 DEG C, more preferably in 60-80 DEG C of condition Lower progress, when reaction carries out in this preferred range, the time of reaction is usually 24-48h.In this method, 1mmol's Compound is usually dissolved with the organic solvent of 6-25mL shown in the formula (III) of compound and 1mmol shown in formula (II).
When being prepared using solvent-thermal method, include mainly:Take compound shown in compound and formula (III) shown in formula (II) molten Solution is subsequently placed in container (being usually the heavy-walled glass pipe or pressure bottle of one end open), in organic solvent through liquid nitrogen frozen After be evacuated to vacuum, sealing after complexation reaction is carried out under heating condition, it is cooling, have crystal precipitation, collect solid, as target is produced Object.In this method, reaction preferably carries out under conditions of >=40 DEG C, is more preferably carried out under the conditions of 60-80 DEG C, when reaction exists When being carried out in this preferred range, the time of reaction is usually 24-48h.When using the method, shown in the formula (II) of 1mmol Compound is usually dissolved with the organic solvent of 5-20mL shown in compound and the formula (III) of 1mmol.
The target product that above-mentioned solvent-thermal method is precipitated is crystal, and the product that solwution method is precipitated is usually powdered, gained Powdered target product further can obtain crystal using the method for solvent crystallization, specially:Powdered target product is set The in the mixed solvent of a kind of composition in a kind of and chloroform and dichloromethane in methanol and ethyl alcohol, under the conditions of 60-80 DEG C 24-48h is reacted, the target product of lenticular is can be obtained after cooling.
The invention also includes above-mentioned 12- chloro benzimidazoles -1,8- naphthalimides-platinum complex or its is pharmaceutically acceptable Salt application in preparation of anti-tumor drugs.
The present invention further comprises a kind of pharmaceutical composition, it contains the above-mentioned 12- chlorobenzenes and miaow of the upper effective dose for the treatment of Azoles -1,8- naphthalimides-platinum complex or its pharmaceutically acceptable salt.
Compared with prior art, the present invention provides a kind of 12- chloro benzimidazoles -1,8- naphthalimides-of structure novel Platinum complex, short preparation period, yield is high, stable quality;Our experimental result show that the complex is to certain cells The inhibitory activity of strain is much higher than its parent nucleus (such as Sk-ov-3) and cis-platinum (such as SMMC-7721), while its poison to normal cell Property is expected to be used for the preparation of antitumor drug well below tumor Drugs (such as cis-platinum and 5 FU 5 fluorouracil).
Description of the drawings
Fig. 1 is the crystal structure figure of final product made from the embodiment of the present invention 1;
Fig. 2 is that compound I and the Topo I of various concentration act on agarose gel electrophoresis figure.
Specific implementation mode
With reference to specific embodiment, the present invention is described in further detail, to more fully understand present disclosure, but The present invention is not limited to following embodiments.
Compound (i.e. 12- chloro benzimidazoles -1,8- naphthalimides) shown in formula (II) involved in following embodiment is pressed Following methods are prepared:
Take 1,8- naphthalene anhydrides (5g, 25.2mmol, 1.0equiv), 4- chlorine o-phenylenediamine (3.59g, 25.2mmol, It 1.0equiv) is placed in 100ml round-bottomed flasks, after 50mL acetic acid is added, reaction is heated to 118 DEG C and is stirred at reflux 6h.Stop anti- It answers, cooled to room temperature, there is yellow solid precipitation, filter, obtain compound (yellow powdery solid) shown in formula (II) 6.7g, yield 87.46%1H NMR (400MHz, DMSO) δ 8.71 (dd, J=14.3,7.4Hz, 2H), 8.54 (d, J= 8.1Hz,1H),8.48–8.29(m,2H),7.98–7.49(m,4H).13C NMR(101MHz,DMSO)δ160.58,151.25, 144.93,136.28,133.11,132.77,132.44,132.38,131.97,131.86,128.72,128.05,127.80, 127.74,127.58,127.08,126.93,123.05,121.38,121.28,120.51,120.32,116.65, 116.55.MS m/z:305.04[M+H]+.
Embodiment 1
Measure 12- chloro benzimidazoles -1,8- naphthalimide (90.14mg, 0.2958mmol), dichloro two (dimethyl sulfoxide) closes Platinum (II) (Pt (DMSO)2Cl2) (124.53mg, 0.2958mmol), 5ml methanol and 5ml chloroforms, it is placed in round-bottomed flask, in temperature Degree is at 60 DEG C, is stirred to react 48h, is filtered to remove unreacting material while hot after reaction, filtrate is cooled to room temperature, and has yellow Solid is precipitated, and collects solid, dry, obtains product as yellow powder 118.07mg, yield 55.00%.
The characterizations such as mass spectrum, elemental analysis and X- single crystal diffractions are carried out to this implementation products therefrom, it is specific as follows:
(1)MS m/z:690.9980[M-Cl+DMSO]+.
(2)Anal.Calc.(for C20H15Cl3N2O2PtS)C 37.02;H 2.33;N 4.32%, Found.C37.04;H 2.30;N 4.32%.
(3) taking this implementation of 10mg products therefrom and 5ml methanol/chloroform mixed solution, (volume ratio of methanol and chloroform is 1: 1) it is placed in tube sealing, is warming up to 90 DEG C, react 12h, it is cooling, there is crystal precipitation, collects crystal, it is dry, obtain yellow crystals.It will Gained yellow crystals are parsed through X-Ray single crystal diffractions, and crystallographic data is as described in Table 1, and part bond distance and bond angle are as follows It states shown in table 2, the crystal structure of products therefrom is as shown in Figure 1.
Table 1:The crystallography and structural modifications data of product
Table 2:The strong length in the part of productWith bond angle [°]
Accordingly, it can be determined that product as yellow powder obtained by the present embodiment is target product 12- chloro benzimidazole -1,8- naphthoyls Imines-platinum complex, shown in structural formula such as following formula (I):
Embodiment 2
Take 12- chloro benzimidazoles -1,8- naphthalimide (304.73mg, 1mmol), Pt (DMSO)2Cl2(422.9mg, It 1mmol) with 12ml methanol, is placed in heavy wall pressure bottle, at being 70 DEG C in temperature after dissolving, is stirred to react 36h, naturally cools to Room temperature has yellow solid precipitation, detaches, dry, obtains yellow powder 371.09mg, yield 51.00%.
Mass spectrum, elemental analysis and the analysis of further X-ray single crystal diffraction are carried out to the present embodiment products therefrom, determined The present embodiment products therefrom is target compound.
Embodiment 3
Take 12- chloro benzimidazoles -1,8- naphthalimide (225.62mg, 0.7404mmol), Pt (DMSO)2Cl2 (311.64mg, 0.7404mmol) and 6ml DMSO, are placed in round-bottomed flask, at being 80 DEG C in temperature after dissolving, are stirred to react For 24 hours, cooled to room temperature has yellow solid precipitation, detaches, dry, obtains yellow powder 285.28mg, yield 53.10%.
Mass spectrum, elemental analysis and the analysis of further X-ray single crystal diffraction are carried out to the present embodiment products therefrom, determined The present embodiment products therefrom is target compound.
Embodiment 4
Take 12- chloro benzimidazoles -1,8- naphthalimide (112.81mg, 0.3702mmol), Pt (DMSO)2Cl2 (155.82mg, 0.3702mmol) and 10ml chloroforms, are placed in round-bottomed flask, at being 80 DEG C in temperature after dissolving, are stirred to react, 40h to be reacted, is filtered to remove unreacting material while hot after reaction, cooled to room temperature has yellow solid precipitation, separation, It is dry, obtain yellow powder 120.88mg, yield 45.00%.
Mass spectrum, elemental analysis and the analysis of further X-ray single crystal diffraction are carried out to the present embodiment products therefrom, determined The present embodiment products therefrom is target compound.
Embodiment 5
Take 12- chloro benzimidazoles -1,8- naphthalimide (112.81mg, 0.3702mmol), Pt (DMSO)2Cl2 (155.82mg, 0.3702mmol), 5ml ethyl alcohol and 5ml dichloromethane, are placed in round-bottomed flask, at being 40 DEG C in temperature, stir 48h to be reacted, is filtered to remove unreacting material while hot after reaction, cooled to room temperature has yellow solid precipitation, separation, It is dry, obtain yellow powder 51.04mg, yield 19.00%.
Mass spectrum, elemental analysis and the analysis of further X-ray single crystal diffraction are carried out to the present embodiment products therefrom, determined The present embodiment products therefrom is target compound.
Embodiment 6
Embodiment 5 is repeated, unlike, reaction temperature is room temperature.
Finally obtain yellow powder 9.75mg, yield 3.63%.
Mass spectrum, elemental analysis and the analysis of further X-ray single crystal diffraction are carried out to the present embodiment products therefrom, determined The present embodiment products therefrom is target compound.
Experimental example 1:Target compound of the present invention tests the anti tumor activity in vitro of a variety of human tumor cell lines:
The antitumor action of 12- chloro benzimidazoles -1, the 8- naphthalimide-platinum complex to illustrate the invention, application People tests (with common antitumor drug 5 FU 5 fluorouracil (5-FU) and cis-platinum the antitumor activity that complex has carried out (Cis-platin) it is reference), and to carrying out the toxicity to normal cell by compound made from 1 the method for above-described embodiment Experiment.
1. the inoculation and culture of cell
Selected cell strain is placed in 37 DEG C, 5%CO2In incubator under the conditions of abundant humidifying, it is inoculated in containing 10% inactivation It is cultivated in the PPMI1640 culture solutions of newborn bovine serum.Cell growth status is observed with inverted microscope, replaces 2-3 training weekly Base is supported, passage in 6-7 days is primary, and when inoculation is passed on 0.25% trypsin digestion, is usually taken passage 3-4 time, is in logarithm life Long-term cell is for testing.
2. the active primary dcreening operation of Compound cellular level
(complex wherein of the present invention is by 1 the method system of above-described embodiment to compound used in this experiment ), all compounds are configured to 100 μ g/mL by purity >=95%, and cosolvent DMSO final concentrations are no more than 1%, it is dense to test this For each compound to the inhibiting rate of cancer cell, all inhibiting rates are more than 50% and meet suppressed (or impaired) form of cell under light microscopic under degree (such as cell shrinkage, the broken, floating) of variation, and be not prodigious compound to normal cell toxicity, then preliminary judgement is The compound primary dcreening operation is effective, i.e., seeks IC into next step50Stage.
3. cell growth inhibition test (mtt assay)
MTT colorimetric methods are a kind of methods of detection cell growth and survival.Testing principle:It is different from dead cell, it is exogenous MTT can be reduced to the bluish violet crystallization first a ceremonial jade-ladle, used in libation (Formazan) of water-insoluble simultaneously by the succinate dehydrogenase in living cells mitochondria It is deposited in cell.Dimethyl sulfoxide (DMSO) (DMSO) can dissolve the first a ceremonial jade-ladle, used in libation in cell, with enzyme-linked immunosorbent assay instrument in 490nm wavelength Place measures its absorbance value, can reflect living cells quantity indirectly.Within the scope of certain cell number, MTT crystallize the amount to be formed with it is thin Born of the same parents' number is directly proportional.This method be widely used in the Activity determinations of some bioactie agents, large-scale screening anti-tumor medicine, Cell toxicity test and tumor radiosensitivity measure etc., have the characteristics that high sensitivity, economic.
The cell in exponential phase is taken, per 180 μ L of hole (about 4500-5000 cell) celliferous culture medium inoculated In 96 well culture plates, in 37 DEG C, 5%CO2It is cultivated for 24 hours under the conditions of abundant humidifying.After cell is adherent, add by the amount of 20 μ L of every hole Enter sample, each sample sets 6 multiple holes, concurrently sets corresponding blank control.Continue after cultivating 48h, 10 μ L are added per hole MTT reagents (a concentration of 5mg/mL) continue after being incubated 4h, and supernatant is abandoned in suction, and 150 μ L DMSO are added per hole, and slight concussion is anti- 5-8min is answered, crystalline particle is made fully to dissolve.Blank control group returns to zero, and removal bias light is measured with 490nm wavelength with microplate reader After absorption value absorbance value (Value), calculating cell proliferation inhibition rate, the test-compound good to primary dcreening operation antitumous effect, after The continuous IC for being continued to do corresponding cell strain with 5 concentration gradients50Value, all experiments are averaged after being repeated 3 times.Experimental result is detailed See below table 3.
From the data in table 3, complex of the present invention is thin to human liver cancer cells Hep G2, human glioma The inhibitory activity of born of the same parents' strain U251 is substantially better than common antitumor drug cis-platinum, and ligands and complexes are to people's normal cell lines of human liver HL- 7702 toxicity is significantly less than cis-platinum.The above result shows that by the way that 12- chloro benzimidazole -1,8- naphthalimide mesh cores are introduced Prepared in the structure of platinum metals novel 12- chloro benzimidazoles -1,8- naphthalimide-platinum antineoplastic complex be it is feasible, The new antitumoral complex of high-efficiency low-toxicity can be filtered out.However, inhibition of the complex of the present invention to all human cancer cells Activity is not all better than its ligand, that is to say, that 12- chloro benzimidazole -1,8- naphthalimide mesh cores are introduced platinum metals Structure differs the cytotoxicity surely improved to tumour cell.
Table 3:Semi-inhibit rate concentration (C of the compound to different tumor cell lines50, μM)
ndaExpression is not tested.
Experimental example 2:The Anticancer Effect and Mechanism of complex of the present invention
The Anticancer Effect and Mechanism of 12- chloro benzimidazoles -1, the 8- naphthalimide-platinum complex to illustrate the invention, Applicant studies the Anticancer Effect and Mechanism of the complex based on topoisomerase I target spot.
1. with topoisomerase I repercussion study
It is a common target of naphthoyl imide compounds and cis-platinum based on topoisomerase, we are solidifying using agarose The interaction of gel electrophoresis and Western blotting research complex and topoisomerase.
Fig. 2 is compound I and Topo the I effect agarose gel electrophoresis figures that various concentration is added.Showing of electrophoresis result Closing object I in vitro has compared with high inhibition effect TopoI, and urging for the TopoI of 0.1U/L can be completely inhibited under 20 μM of concentration Change function, compound can completely inhibit topoisomerase I activity at 80 μM.Classical Topo I toxic agents camptothecine (T) in vitro for The 503nhibiting concentration of topoisomerase I is about 17 μM, and compound I is suitable with its to the inhibitory activity of topoisomerase I.
Fig. 2 experiments show that compound I has stronger topoisomerase enzyme inhibition activity, therefore it is presumed that it plays anticancer work Property may be by inhibiting the activity of intracellular topoisomerase.

Claims (7)

1. compound or its pharmaceutically acceptable salt shown in following formula (I)s:
2. the preparation method of compound described in claim 1, it is characterised in that:It mainly includes the following steps that:Take following formula (II) Compound is placed in organic solvent shown in shown compound and formula (III), and complexation reaction is carried out under the conditions of being heated or not heated, Up to target product;
3. the preparation method of compound according to claim 1, it is characterised in that:The organic solvent be selected from methanol, The combination of one or more of ethyl alcohol, chloroform, dichloromethane, dimethyl sulfoxide (DMSO) and n,N-Dimethylformamide.
4. the preparation method of compound according to claim 1, it is characterised in that:It is described reaction under conditions of >=40 DEG C into Row.
5. the preparation method of compound according to claim 1, it is characterised in that:It is described reaction under the conditions of 60-80 DEG C into Row.
6. compound described in claim 1 or its pharmaceutically acceptable salt application in preparation of anti-tumor drugs.
7. a kind of pharmaceutical composition, it is characterised in that:Compound or its medicine described in claim 1 containing the upper effective dose for the treatment of Acceptable salt on.
CN201810729521.9A 2018-07-05 2018-07-05 12-chlorobenzimidazole-1, 8-naphthalimide-platinum complex and preparation method and application thereof Active CN108623638B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201810729521.9A CN108623638B (en) 2018-07-05 2018-07-05 12-chlorobenzimidazole-1, 8-naphthalimide-platinum complex and preparation method and application thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201810729521.9A CN108623638B (en) 2018-07-05 2018-07-05 12-chlorobenzimidazole-1, 8-naphthalimide-platinum complex and preparation method and application thereof

Publications (2)

Publication Number Publication Date
CN108623638A true CN108623638A (en) 2018-10-09
CN108623638B CN108623638B (en) 2020-09-29

Family

ID=63688809

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201810729521.9A Active CN108623638B (en) 2018-07-05 2018-07-05 12-chlorobenzimidazole-1, 8-naphthalimide-platinum complex and preparation method and application thereof

Country Status (1)

Country Link
CN (1) CN108623638B (en)

Citations (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4394129A (en) * 1979-08-24 1983-07-19 Hoechst Aktiengesellschaft Process for the finishing of fibrous materials: sulfonyl- or carbonyl-cyanamides of dyestuffs
US5066796A (en) * 1990-05-31 1991-11-19 Xerox Corporation Electrophotographic imaging members with bichromophoric bisazo phthalocyanine photoconductive materials
EP1000998A1 (en) * 1998-11-09 2000-05-17 Toray Industries, Inc. Electroluminescent element and devices
JP2001223082A (en) * 2000-02-08 2001-08-17 Toray Ind Inc Light emitting element
JP2004155728A (en) * 2002-11-07 2004-06-03 Mitsubishi Chemicals Corp Method for producing metal complex
CN102206203A (en) * 2011-04-04 2011-10-05 大连理工大学 Synthesis of benzimidazole-containing naphthalimide derivatives and applications of benzimidazole-containing naphthalimide derivatives on cancer resistance
CN104447876A (en) * 2014-11-25 2015-03-25 南京工业大学 Platinum (II) alkyne complex and application thereof
CN104558054A (en) * 2014-12-12 2015-04-29 广西师范大学 Metal complex taking oxidized nantenine as ligand and synthetic method and applications thereof
CN104610372A (en) * 2015-02-13 2015-05-13 桂林医学院附属医院 Synthesis method and application of platinum (II) complex using 2-benzoylpyridine as ligand
WO2016028225A1 (en) * 2014-08-22 2016-02-25 Nanyang Technological University Platinum complexes as anticancer agents
CN105669763A (en) * 2015-12-30 2016-06-15 广西师范大学 9-amino oxidized isoaporphine-platinum (II) complex, synthetic method and application thereof
CN107746418A (en) * 2017-09-27 2018-03-02 玉林师范学院 A kind of synthesis and its application of 9 chlorine 1,2,3,4 tetrahydro acridine platinum (II) complex for targeting liver cancer
CN108033912A (en) * 2017-12-28 2018-05-15 广西师范大学 Low 1,8- Naphthalamide derivatives of a kind of toxicity and its preparation method and application

Patent Citations (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4394129A (en) * 1979-08-24 1983-07-19 Hoechst Aktiengesellschaft Process for the finishing of fibrous materials: sulfonyl- or carbonyl-cyanamides of dyestuffs
US5066796A (en) * 1990-05-31 1991-11-19 Xerox Corporation Electrophotographic imaging members with bichromophoric bisazo phthalocyanine photoconductive materials
EP1000998A1 (en) * 1998-11-09 2000-05-17 Toray Industries, Inc. Electroluminescent element and devices
JP2001223082A (en) * 2000-02-08 2001-08-17 Toray Ind Inc Light emitting element
JP2004155728A (en) * 2002-11-07 2004-06-03 Mitsubishi Chemicals Corp Method for producing metal complex
CN102206203A (en) * 2011-04-04 2011-10-05 大连理工大学 Synthesis of benzimidazole-containing naphthalimide derivatives and applications of benzimidazole-containing naphthalimide derivatives on cancer resistance
WO2016028225A1 (en) * 2014-08-22 2016-02-25 Nanyang Technological University Platinum complexes as anticancer agents
CN104447876A (en) * 2014-11-25 2015-03-25 南京工业大学 Platinum (II) alkyne complex and application thereof
CN104558054A (en) * 2014-12-12 2015-04-29 广西师范大学 Metal complex taking oxidized nantenine as ligand and synthetic method and applications thereof
CN104610372A (en) * 2015-02-13 2015-05-13 桂林医学院附属医院 Synthesis method and application of platinum (II) complex using 2-benzoylpyridine as ligand
CN105669763A (en) * 2015-12-30 2016-06-15 广西师范大学 9-amino oxidized isoaporphine-platinum (II) complex, synthetic method and application thereof
CN107746418A (en) * 2017-09-27 2018-03-02 玉林师范学院 A kind of synthesis and its application of 9 chlorine 1,2,3,4 tetrahydro acridine platinum (II) complex for targeting liver cancer
CN108033912A (en) * 2017-12-28 2018-05-15 广西师范大学 Low 1,8- Naphthalamide derivatives of a kind of toxicity and its preparation method and application

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
MEENAKSHI VERMA等,: "Synthesis, in vitro evaluation and molecular modelling of naphthalimide analogue as anticancer agents", 《EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY》 *

Also Published As

Publication number Publication date
CN108623638B (en) 2020-09-29

Similar Documents

Publication Publication Date Title
CN107955042B (en) Platinum complex with anticancer activity, preparation method and application
CN106632424B (en) Using 1- (2- pyridines) -9- benzyls-B-carboline as the chlorination copper complex and its synthetic method of ligand and application
CN104774221B (en) Metal complexes of quinolinone derivatives, synthesis method and applications thereof
CN107827934B (en) Tetravalent platinum complex with anticancer activity, preparation method and application
CN106632421B (en) The copper-nitrate complex and its synthetic method of 1- (2- pyridines) -9- (4- methylbenzyls)-B-carboline and application
CN106632420B (en) Using 1- (2- pyridines) -9- butyl-ss-carbolines as the chlorination copper complex and its synthetic method of ligand and application
CN104725431B (en) Cobalt (II) complex of quinolinone derivative, and synthesis method and application thereof
CN108623638A (en) 12- chloro benzimidazoles -1,8- naphthalimides-platinum complex and its preparation method and application
CN108727434A (en) 11- trifluoro methyl benzimidazoles -1,8- naphthalimides-platinum complex and its preparation method and application
CN109021021A (en) 11,12- dichloro benzimidazole -1,8- naphthalimide-platinum complex and its preparation method and application
CN106478687B (en) Using 1- (2- pyridines) -9- ethyl-beta-carbolines as the chlorination copper complex and its synthetic method of ligand and application
CN109021020A (en) 11,12- dimethylbenzimidazole -1,8- naphthalimide-platinum complex and its preparation method and application
CN108727435A (en) 12- fluorobenzimidazoles -1,8- naphthalimides-platinum complex and its preparation method and application
CN108752384A (en) Benzimidazole -1,8- naphthalimides-platinum complex and its preparation method and application
CN106478689B (en) The chlorination copper complex of 1- (2- pyridines) -9- (4- methyl-benzyls)-B-carboline and its synthetic method and application
CN106632416B (en) Using 1- (2- pyridines) -9- isopentyl-B-carboline as the chlorination copper complex and its synthetic method of ligand and application
CN106632422B (en) The chlorination copper complex and its synthetic method of 1- (2- pyridines) -9- (3- phenyl propyls)-B-carboline and application
CN106632418B (en) Using 1- (2- pyridines) -9- octyls-B-carboline as the chlorination copper complex and its synthetic method of ligand and application
CN106478683B (en) Using 1- (2- pyridines) -9- isobutyl groups-B-carboline as the chlorination copper complex and its synthetic method of ligand and application
CN106478685B (en) Using 1- (2- pyridines) -9- propyl-B-carboline as the chlorination copper complex and its synthetic method of ligand and application
CN106632419B (en) Using 1- (2- pyridines) -9- hexyls-B-carboline as the chlorination copper complex and its synthetic method of ligand and application
CN106432289B (en) Using 1 (2 pyridine) 9 amyl group β carbolines as the chlorination copper complex and its synthetic method of part and application
CN106632417B (en) Using 1- (2- pyridines) -9- nonyls-B-carboline as the chlorination copper complex and its synthetic method of ligand and application
CN106478680B (en) The chlorination copper complex and its synthetic method of 1- (2- pyridines) -9- Cvclopropvlmethvls-B-carboline and application
CN106478691B (en) The chlorination copper complex and its synthetic method of 1- (2- pyridines) -9- (2- phenylethyls)-B-carboline and application

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for 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: 20211231

Address after: 253000 Jinghua Avenue, songguantun sub district office, Dezhou Economic and Technological Development Zone, Shandong Province

Patentee after: Dezhou Luotai Trading Co.,Ltd.

Address before: 541004 No. two, 109 North Road, Guilin, the Guangxi Zhuang Autonomous Region

Patentee before: GUILIN MEDICAL University

TR01 Transfer of patent right