CN105384702B - Three substitution s-triazine compounds and preparation method thereof - Google Patents
Three substitution s-triazine compounds and preparation method thereof Download PDFInfo
- Publication number
- CN105384702B CN105384702B CN201510920677.1A CN201510920677A CN105384702B CN 105384702 B CN105384702 B CN 105384702B CN 201510920677 A CN201510920677 A CN 201510920677A CN 105384702 B CN105384702 B CN 105384702B
- Authority
- CN
- China
- Prior art keywords
- compound
- formula
- preparation
- hydrogen
- hydrochloride
- 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.)
- Expired - Fee Related
Links
- RSPANIAHKYHBKR-UHFFFAOYSA-N COc(cc(Cc1nc(N2CCCC2)nc(N)n1)cc1)c1O Chemical compound COc(cc(Cc1nc(N2CCCC2)nc(N)n1)cc1)c1O RSPANIAHKYHBKR-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D251/00—Heterocyclic compounds containing 1,3,5-triazine rings
- C07D251/02—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings
- C07D251/12—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D251/14—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hydrogen or carbon atoms directly attached to at least one ring carbon atom
- C07D251/16—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hydrogen or carbon atoms directly attached to at least one ring carbon atom to only one ring carbon atom
- C07D251/18—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hydrogen or carbon atoms directly attached to at least one ring carbon atom to only one ring carbon atom with nitrogen atoms directly attached to the two other ring carbon atoms, e.g. guanamines
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention provides one kind three and substitutes s-triazine compound, by the hydrochloride of biguanide compound and 1, the mixing of 1 dibromoethylene class compound is added in organic solvent, under the catalysis of metallic copper, in the presence of part and alkali, stirring reaction 2~25 hours at a temperature of 60~130 DEG C, target compound is made through handling.The preparation method for developing three novel substitution s-triazine compounds of structure of the present invention, the technological reaction mild condition, easy to operate, cost is low, there is extensive prospects for commercial application.Three substitutions s-triazine compound provided by the present invention shows certain anti-breast cancer activity, is laid a good foundation for new medicament screen and exploitation, has preferable practical value.General structure is as follows.
Description
Technical field
The invention belongs to chemical field, is related to a kind of three new substitution s-triazine compounds and its preparation.
Background technology
S-triazine compound is widely used in the industries such as medicine, weaving, rubber, as antiseptic, insecticide, activity
Dyestuff, fluorescent whitening agent, luminescent material, explosive and catalyst etc., its route of synthesis be mainly the ring of nitrile compounds it is poly- and
Therefore, the three substitution s-triazine compounds for preparing novelty have important theory significance and reality to the modification of s-triazine side chain
Application value.
The content of the invention
It is an object of the invention to provide a kind of three new substitution s-triazine compounds, general structure are as follows：
R in formula (III)1, R2Each stand alone as hydrogen, C1~C10 alkyl or C6~C10 aryl, or R1, R2With both it
Between N combine the heterocycle to form C4~C8 containing N or containing N, O；It is preferred that R1, R2Each stand alone as hydrogen or methyl, or R1, R2With
N between the two combines to form nafoxidine ring, piperidine ring or morpholine ring.R3, R4Each stand alone as hydrogen, C1~C10 alkyl or C6
~C10 aryl；It is preferred that R3, R4Each stand alone as hydrogen or methyl.R5For C6~C10 aryl；Further R5For substituted-phenyl；It is preferred that R5
For 3,4- Dimethoxyphenyls, rubigan or p-bromophenyl.
It is a further object to provide the compound (III) preparation method, realized by following steps：
By the hydrochloride of the biguanide compound shown in formula (I) with 1,1- dibromoethylenes class compound shown in formula (II) are mixed
Close and add in organic solvent, under the catalytic action of metallic copper, in the presence of part and alkali, stirred at a temperature of 60~130 DEG C
Mix reaction 2~25 hours, after reaction terminates, three substitution compound in triazine class shown in formula (III) are made in reaction solution post processing.Instead
Answer formula as follows：
The organic solvent is ethers；The metal copper catalyst is the halide of copper or the oxide of copper；The part
For aromatic nitrogen heterocycle, carbonyl containing compound or amino acid；The alkali is inorganic base；1,1- dibromoethylene classizationes shown in formula (II) with
The hydrochloride (not including Metformin) of biguanide compound shown in formula (I), metal copper catalyst, part, alkalescence
The amount ratio of the material of material is 1：0.5~3.0：0.05~0.5：0.3~0.1：8.0~4.0.
Wherein R1, R2Each stand alone as hydrogen, C1~C10 alkyl or C6~C10 aryl, or R1, R2N between the two
Combination forms the heterocycle of C4~C8 containing N or containing N, O；It is preferred that R1, R2Each hydrogen, methyl are stood alone as (not including R1, R2It is simultaneously
Methyl, R3, R4It is simultaneously hydrogen atom；And R1, R2It is simultaneously hydrogen atom, R3, R4It is simultaneously methyl), or R1, R2With both it
Between N combine to form nafoxidine ring, piperidine ring or morpholine ring.R3, R4Each stand alone as hydrogen, C1~C10 alkyl or C6~C10
Aryl；It is preferred that R3, R4Each stand alone as hydrogen or methyl.R5For C6~C10 aryl；It is preferred that R5For substituted-phenyl；Further preferred R5
For 3,4- Dimethoxyphenyls, rubigan or p-bromophenyl.
Described organic solvent is ethers；Preferably tetrahydrofuran and 1,4- dioxane；More preferably 1,4- bis-
The ring of oxygen six.The volumetric usage of the organic solvent is generally calculated as with the quality of the 1,1- dibromoethylene class compounds shown in formula (II)
10~50mL/g.
Described metal copper catalyst is the halide of copper or the oxide of copper；Preferably cuprous iodide or cuprous oxide.
The part is aromatic nitrogen heterocycle, carbonyl containing compound or amino acid；Preferably 2,2 '-bipyridyl, ninhydrin or
Glycine.
Described alkali is inorganic base；Preferably potassium phosphate.
In preparation method of the present invention, the post processing can be with the following method：After reaction terminates, reacting liquid filtering,
Filter residue is washed with methanol, concentrates filtrate, column chromatography (dichloromethane:Methanol=50:1, V:V), washing containing target compound is collected
De- liquid, is evaporated under reduced pressure, is dried to obtain target compound (III).
It is also another object of the present invention to provide the compound (III) to prepare the application in treating breast cancer medicines.
The preparation method for developing three novel substitution s-triazine compounds of structure of the present invention, the technological reaction condition
Gently, easy to operate, cost is low, there is extensive prospects for commercial application.Three substitutions s-triazine chemical combination provided by the present invention
Thing shows certain anti-breast cancer activity, is laid a good foundation for new medicament screen and exploitation, has preferable practical value.
Embodiment
Below will by embodiment, the present invention is further illustrated, but protection scope of the present invention not limited to this.
Embodiment 1：The preparation of compound (III-1)
Piperidines biguanide hydrochloride (0.2057g), 1,1- dibromo (3,4- dimethoxy) styrene are added in reaction vessel
(0.1286g), cuprous iodide (0.0076g), 2,2 '-bipyridyl (0.0125g), potassium phosphate (0.5094g), in Isosorbide-5-Nitrae-dioxy six
Mixed in ring (5mL), stirring reaction 13 hours in 110 DEG C of oil baths；After reaction terminates, filtering, filter residue is washed with methanol, concentration filter
Liquid, column chromatography (dichloromethane:Methanol=50:1) R, is collectedfThe eluent of value 0.3~0.35, it is evaporated under reduced pressure, is dried to obtain mesh
Mark compound III-1 (0.1067g, yield 81%).
1H NMR(500MHz,CDCl3):δ 6.99 (d, J=1.8Hz, 1H), 6.90 (dd, J=8.2,1.8Hz, 1H),
6.80 (d, J=8.2Hz, 1H), 5.16 (s, 2H), 3.87 (s, 3H), 3.86 (s, 3H), 3.75-3.73 (m, 6H), 1.66 (t, J
=5.4Hz 2H), 1.61-1.49 (m, 4H).
Embodiment 2：
The amount of cuprous iodide is changed to 0.0048g, other operations are the same as embodiment 1, the amount of obtaining 0.013g, yield 10%.
Embodiment 3：
The amount of cuprous iodide is changed to 0.0189g, other operations are the same as embodiment 1, the amount of obtaining 0.0988g, yield 75%.
Embodiment 4：
The amount of piperidines biguanide hydrochloride is changed to 0.308g, other operations are with embodiment 1, the amount of obtaining 0.079g, yield
60%.
Embodiment 5：
The amount of piperidines biguanide hydrochloride is changed to 0.103g, other operations are with embodiment 1, the amount of obtaining 0.0105g, yield
8%.
Embodiment 6：
The amount of 2,2 '-bipyridyl is changed to 0.0076g, other operations are with embodiment 1, the amount of obtaining 0.0527g, yield
40%.
Embodiment 7：
The amount of 2,2 '-bipyridyl is changed to 0.0234g, other operations are with embodiment 1, the amount of obtaining 0.0724g, yield
55%.
Embodiment 8：
The amount of potassium phosphate is changed to 0.4246g, other operations are the same as embodiment 1, the amount of obtaining 0.0803g, yield 61%.
Embodiment 9：
The amount of potassium phosphate is changed to 0.8491g, other operations are the same as embodiment 1, the amount of obtaining 0.1001g, yield 76%.
Embodiment 10：
Reaction temperature is reduced to 60 DEG C, other operations are the same as embodiment 1, the amount of obtaining 0.0206g, yield 10%.
Embodiment 11：
Reaction temperature is increased to 130 DEG C, other operations are the same as embodiment 1, the amount of obtaining 0.0658g, yield 50%.
Embodiment 12：The preparation of compound (III-2)
Operation with embodiment 1, simply by piperidines biguanide hydrochloride change into nafoxidine biguanide hydrochloride (0.1917g,
1.00mmol), 2,2 '-bipyridyl changes ninhydrin (0.0128g, 0.08mmol) into, and target compound III-2 is made
(0.0946g, yield 75%).1H NMR(500MHz,CDCl3):δ 6.99 (d, J=1.8Hz, 1H), 6.91 (dd, J=8.1,
1.8Hz, 1H), 6.79 (d, J=8.1Hz, 1H), 5.28 (s, 2H), 3.87 (s, 3H), 3.85 (s, 3H), 3.74 (s, 2H),
3.58 (t, J=6.4Hz, 2H), 3.47 (t, J=6.4Hz, 2H), 2.02-1.83 (m, 4H).
Embodiment 13：The preparation of compound (III-3)
Operation changes abitilguanide hydrochloride (0.2077g, 1.00mmol) into embodiment 1, simply piperidines biguanide hydrochloride,
2,2 '-bipyridyl changes ninhydrin (0.0128g, 0.08mmol) into, and target compound III-3 is made, and (0.1087g, yield are
82%).1H NMR(500MHz,CDCl3):δ 6.93 (d, J=1.6Hz, 1H), 6.88 (dd, J=8.2,1.6Hz, 1H), 6.80
(d, J=8.2Hz, 1H), 5.26 (s, 2H), 3.86 (s, 3H), 3.86 (s, 3H), 3.84-3.74 (m, 4H), 3.74 (s, 2H),
3.72–3.69(m,4H)。
Embodiment 14：The preparation of compound (III-4)
Operation simply changes piperidines biguanide hydrochloride into N, N, N with embodiment 1 ', N '-tetramethyl biguanide hydrochloride
(0.1937g, 1.00mmol), 2,2 '-bipyridyl is changed to glycine (0.0060g, 0.08mmol), and target compound III- is made
5 (0.0546g, yields 43%).
1H NMR(500MHz,CDCl3):δ 7.07 (d, J=1.8Hz, 1H), 6.94 (dd, J=8.1,1.8Hz, 1H),
6.79 (d, J=8.1Hz, 1H), 3.88 (s, 3H), 3.86 (s, 3H), 3.76 (s, 2H), 3.13 (s, 12H).
Embodiment 15：The preparation of compound (III-5)
Operation changes 1,1-, bis- bromo- styrene into embodiment 1, simply 1,1- dibromos (3 ', 4 '-dimethoxy) styrene
(0.1048g, 0.40mmol), change piperidines biguanide hydrochloride into abitilguanide hydrochloride (0.2077g, 1.00mmol), be made
Target compound III-7 (0.0847g, yield 78%).
1H NMR(500MHz,CDCl3):δ 7.35 (d, J=7.3Hz, 2H), 7.31 (t, J=7.3Hz, 2H), 7.23 (t, J
=7.2Hz, 1H), 5.24 (s, 2H), 3.81-3.79 (m, 6H), 3.72-3.69 (m, 4H).
Embodiment 16：The preparation of compound (III-6)
Operation changes 1,1- dibromos (4 '-chlorine) benzene into embodiment 1, simply 1,1- dibromos (3 ', 4 '-dimethoxy) styrene
Ethene (0.1186g, 0.40mmol), change piperidines biguanide hydrochloride into abitilguanide hydrochloride (0.2077g, 1.00mmol),
Target compound III-8 (0.0929g, yield 76%) is made.
1H NMR(500MHz,CDCl3):δ7.31–7.23(m,4H),5.35(s,2H),3.78–3.76(m,6H),3.72–
3.66(m,4H)。
Embodiment 17：The preparation of compound (III-7)
Operation changes 1,1- dibromos (4 '-bromine) benzene into embodiment 1, simply 1,1- dibromos (3 ', 4 '-dimethoxy) styrene
Ethene (0.1363g, 0.40mmol), change piperidines biguanide hydrochloride into abitilguanide hydrochloride (0.2077g, 1.00mmol),
Target compound III-9 (0.0882g, yield 63%) is made.
1H NMR(500MHz,CDCl3):δ 7.41 (d, J=8.3Hz, 2H), 7.22 (d, J=8.3Hz, 2H), 5.20 (s,
2H),3.78-3.75(m,6H),3.72–3.68(m,4H)。
Embodiment 18：Anti-breast cancer cell MDA-MB-231 biological activity tests
External anti-breast cancer cell MDA-MB-231 activity test methods：Mtt assay
A principles：Thiazolyl blue (MTT) is decomposed into bluish violet crystallization not soluble in water simultaneously by cell by mitochondria hydrolase
It is deposited in cell, crystal can determine the suction of its light with enzyme-linked immunosorbent assay instrument by dmso solution at 490nm wavelength
Receipts value, reflect the proliferative conditions and number change of cell indirectly.
B cells：Breast cancer cell MDA-MB-231 (is purchased from Chinese Academy of Sciences's Shanghai school of life and health sciences cell bank)
C experimental procedures：
1) preparation of sample：For solvable sample, dissolved per 1mg with 20 μ L DMSO, take 2uL dilute with 1000 μ L nutrient solutions
Release, it is 100 μ g/mL to make concentration, then with nutrient solution serial dilution to concentration.
2) culture of cell
2.1) preparation of culture medium：Contain 800,000 units of Penicillin, 1.0g streptomysins, 10% inactivation in per 1000mL culture mediums
Hyclone.
2.2) culture of cell：By tumor cell inoculation in culture medium, 37 DEG C are put, 5%CO2Cultivated in incubator, 3~
5d is passed on.
3) inhibitory action of the determination sample to growth of tumour cell
Cell is digested with EDTA- pancreatin digestive juice, and 1 × 10 is diluted to culture medium5/ mL, it is added to 96 hole cell trainings
Support in plate, per hole 100uL, put 37 DEG C, 5%CO2Cultivated in incubator.After being inoculated with 24h, sample that addition is diluted with culture medium,
Per the μ L of hole 100, each concentration adds 3 holes, puts 37 DEG C, 5%CO2Cultivated in incubator, add 5mg/ after 72h in cell culture well
ML MTT, per the μ L of hole 10,37 DEG C of incubation 4h to be put, DMSO is added, per the μ L of hole 150, is vibrated with oscillator, Shi Jia Za is completely dissolved,
With ELIASA under 570nm wavelength colorimetric.With similarity condition with being free of sample, the medium culture containing same concentration DMSO it is thin
Born of the same parents calculate LC50 (IC of the sample to growth of tumour cell as control50), as a result as shown in table 1.
Using breast cancer cell MDA-MB-231 as model, using cis-platinum as positive reference substance, determine what is prepared in embodiment
Biphenol compound (III) sample is in vitro to the inhibitory action of breast cancer cell growth.As a result show, part of compounds (III) is right
Experiment breast cancer cell MDA-MB-231 used has certain inhibitory action (the results detailed in Table 1).
IC of the compound of table 1 (III) to MDA-MB-23150(μM)
| Test No. | Compound | IC50 |
| 1 | III-1 | 9.06 |
| 2 | III-5 | 0.66 |
| 3 | III-8 | 1.22 |
| 4 | Comparison medicine (cis-platinum) | 8.21 |
Claims (4)
1. a kind of preparation method of three substitutions s-triazine compound, it is characterised in that realized by following steps：
By the hydrochloride of the biguanide compound shown in formula (I) with 1, the 1- dibromoethylene class compounds shown in formula (II) are mixed
Close and add in organic solvent, under the catalytic action of metallic copper, in the presence of part and alkali, stirred at a temperature of 60~130 DEG C
Mix reaction 2 ~ 25 hours, after reaction terminates, formula is made in reaction solution post processing（III）Three shown substitution compound in triazine class, instead
Answer formula as follows：
The organic solvent is selected from tetrahydrofuran or Isosorbide-5-Nitrae-dioxane, and the volumetric usage of organic solvent is with shown in formula (II)
The quality of 1,1- dibromoethylene class compound is calculated as 10 ~ 50mL/g；Described metal copper catalyst is selected from cuprous iodide or oxidation
It is cuprous；The part is selected from 2,2 '-bipyridyl, ninhydrin or glycine；Described alkali is selected from potassium phosphate, shown in formula (II)
1,1- dibromoethylene class compound and formula（I）The hydrochloride of shown biguanide compound, metal copper catalyst, part, alkali
The mass ratio of material is 1：0.5~3.0：0.05~0.5：0.3~0.1：4.0~8.0；
Wherein R1, R2Each stand alone as hydrogen, C1 ~ C10 alkyl or C6 ~ C10 aryl, or R1, R2N between the two combines to be formed
The heterocycle of C4 ~ C8 containing N or containing N, O；R3, R4Each stand alone as hydrogen, C1 ~ C10 alkyl or C6 ~ C10 aryl；R5For 3,4- diformazans
Phenyl, rubigan or p-bromophenyl.
2. preparation method according to claim 1, it is characterised in that formula（I）The hydrochloride of shown biguanide compound
Do not include Metformin.
3. preparation method according to claim 1, it is characterised in that R1, R2Each stand alone as hydrogen, methyl；R3, R4Each solely
Stand as hydrogen or methyl, and do not include R1, R2It is simultaneously methyl, R3, R4It is simultaneously hydrogen atom.
4. preparation method according to claim 1, it is characterised in that the post processing is with the following method：Reaction terminates
Afterwards, reacting liquid filtering, filter residue are washed with methanol, concentration filtrate, column chromatography, and the volume ratio of dichloromethane and methanol is 50:1, receive
Collect the eluent containing target compound, be evaporated under reduced pressure, be dried to obtain target compound（III）.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510920677.1A CN105384702B (en) | 2015-12-11 | 2015-12-11 | Three substitution s-triazine compounds and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510920677.1A CN105384702B (en) | 2015-12-11 | 2015-12-11 | Three substitution s-triazine compounds and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN105384702A CN105384702A (en) | 2016-03-09 |
| CN105384702B true CN105384702B (en) | 2018-04-10 |
Family
ID=55417527
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510920677.1A Expired - Fee Related CN105384702B (en) | 2015-12-11 | 2015-12-11 | Three substitution s-triazine compounds and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105384702B (en) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105732528B (en) * | 2016-03-25 | 2018-11-13 | 浙江工业大学 | Preparation method of 2-arylamine-4-dimethylamine-1, 3, 5-triazine compound |
| CN108546252A (en) * | 2018-05-02 | 2018-09-18 | 浙江工业大学 | Triazinone compound and preparation method and application thereof |
| CN108840829A (en) * | 2018-05-02 | 2018-11-20 | 浙江工业大学 | Preparation method of 4-aryl-1, 3, 5-triazine-2-ketone compound |
| CN108752284A (en) * | 2018-06-29 | 2018-11-06 | 浙江工业大学 | Two amido-s- compound in triazine class of one kind and its preparation method and application |
| CN110511214B (en) * | 2019-06-28 | 2021-07-27 | 浙江工业大学 | Diamine substituted aromatic heterocyclic compound and preparation method and application thereof |
| CN113288899B (en) * | 2021-05-17 | 2022-10-11 | 浙江工业大学 | Application of heterocyclic thiol compound in preparation of antitumor drugs |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001047897A1 (en) * | 1999-12-28 | 2001-07-05 | Pharmacopeia, Inc. | Cytokine, especially tnf-alpha, inhibitors |
| US20020065270A1 (en) * | 1999-12-28 | 2002-05-30 | Moriarty Kevin Joseph | N-heterocyclic inhibitors of TNF-alpha expression |
| HUP0400908A3 (en) * | 2000-12-21 | 2010-03-29 | Vertex Pharma | Pyrazole compounds useful as protein kinase inhibitors, their use and pharmaceutical compositions containing them |
| US6887873B2 (en) * | 2001-03-23 | 2005-05-03 | Aventis Pharma S.A. | Triazine derivatives and their application as antitelomerase agents |
| CN101307029B (en) * | 2008-07-08 | 2011-04-13 | 浙江大学 | 2,4,6-tri-substituted-1,3,5-triazine derivates library and preparation method |
| WO2013102431A1 (en) * | 2012-01-06 | 2013-07-11 | Agios Pharmaceuticals, Inc. | Therapeutically active compounds and their methods of use |
-
2015
- 2015-12-11 CN CN201510920677.1A patent/CN105384702B/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| CN105384702A (en) | 2016-03-09 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN105384702B (en) | Three substitution s-triazine compounds and preparation method thereof | |
| CN105399695B (en) | Compound in triazine class and its preparation method and application | |
| CN110713500B (en) | Palladium complex using 2-benzoylpyridine thiosemicarbazone and synthetic method thereof | |
| CN108752284A (en) | Two amido-s- compound in triazine class of one kind and its preparation method and application | |
| CN109053612A (en) | A kind of phenethyl replaces 1,3,5- compound in triazine class and its preparation method and application | |
| CN110002987A (en) | Phenyl acrol cyclohexenone derivates and preparation method and purposes | |
| CN103396386B (en) | Two replacement dinaphtho [2,1-b:1 ', 2 '-d] furan derivative and its preparation method and application | |
| CN110372754A (en) | A kind of novel metal complex of iridium and its preparation method and application | |
| CN108546252A (en) | Triazinone compound and preparation method and application thereof | |
| CN108794414A (en) | The s-triazine compound of aromatic amide substitution and preparation and application | |
| CN105968064B (en) | Two tolyl tetrazine diformamide compounds of one kind and preparation and application | |
| CN105503754B (en) | The triazine of 2 amino, 4 benzyl, 6 morpholine 1,3,5 and its preparation and application | |
| CN103275022A (en) | 1-benzyl-1, 2, 3-triazole compound, as well as preparation method and application thereof | |
| CN110511214A (en) | Diamine substituted aromatic heterocyclic compound and preparation method and application thereof | |
| CN108530436B (en) | Pyrazole compound and preparation method and application thereof | |
| CN107827934B (en) | Tetravalent platinum complex with anticancer activity, preparation method and application | |
| CN103275023B (en) | 1-aryl-1,2,3-triazole compound and Synthesis and applications thereof | |
| CN105949139B (en) | A kind of sec-butyl diphenyl tetrazine benzamide compound and preparation and application | |
| CN102796094B (en) | Dihalofluorescein derivative and application thereof | |
| CN104910074A (en) | Hydroximic acid group-containing pyrazoles derivative, preparation method and purpose thereof | |
| CN101967163B (en) | Platinum (II) anti-cancer compound with selectivity for cancer cells | |
| CN112341479A (en) | Synthetic method and application of binuclear zinc complex | |
| CN107311949B (en) | Sulfonamide-substituted aryl triazine compound and preparation method and application thereof | |
| CN104817489A (en) | Heterocyclic biphenyl aryl urea compound with antitumor activity, preparation method and application thereof | |
| CN105130896B (en) | The naphthalimide derivative of a kind of substituent containing thiocarbamide, 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 | ||
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20180410 Termination date: 20211211 |