CN104072493A - Naphthalimide compound containing 2-mercaptobenzothiazole and triazole heterocycle, preparation method and application thereof - Google Patents
Naphthalimide compound containing 2-mercaptobenzothiazole and triazole heterocycle, preparation method and application thereof Download PDFInfo
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- CN104072493A CN104072493A CN201410246653.8A CN201410246653A CN104072493A CN 104072493 A CN104072493 A CN 104072493A CN 201410246653 A CN201410246653 A CN 201410246653A CN 104072493 A CN104072493 A CN 104072493A
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- 0 *c(c1cccc(C(O2)=O)c11)ccc1C2=O Chemical compound *c(c1cccc(C(O2)=O)c11)ccc1C2=O 0.000 description 1
- ZREGBQAMBHEDOQ-UHFFFAOYSA-N O=C(c(c1c2cc3)cccc1c3-[n]1nnc(CSc3nc4ccccc4[s]3)c1)OC2=O Chemical compound O=C(c(c1c2cc3)cccc1c3-[n]1nnc(CSc3nc4ccccc4[s]3)c1)OC2=O ZREGBQAMBHEDOQ-UHFFFAOYSA-N 0.000 description 1
- DTUOTSLAFJCQHN-UHFFFAOYSA-N O=C(c(c1c2cc3)cccc1c3Br)OC2=O Chemical compound O=C(c(c1c2cc3)cccc1c3Br)OC2=O DTUOTSLAFJCQHN-UHFFFAOYSA-N 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
Abstract
The invention relates to a naphthalimide compound containing 2-mercaptobenzothiazole and triazole heterocycle, and application of the naphthalimide compound. The compound has a structure as shown in the general formula Y. According to the compound, five-membered triazolecycle is introduced in a non-naphtho mode to increase a conjugate area of a naphthalimide parent and simultaneously is connected with an active group which is mercaptobenzothiazole so as to design and synthetize a compound with wide antineoplastic activity. The compound takes good suppression effect on normal growth of tumor cells based on different tissue sources such as cervical cancer, liver cancer and breast cancer.
Description
Technical field
The present invention relates to naphthalimide compound, its preparation method and the application thereof containing 2-mercaptobenzothiazole and triazole heterocycle of a class in biological organic synthesis field.
Background technology
Early 1970s,
research group has designed and synthesized a series of 3-nitro-naphthalene imide derivatives for the first time, and these compounds has been carried out to the anti-tumor test of in vitro and in vivo.Wherein pacifying how Fitow (Amonafide) and Mitonafide (Mitonafide) is two very famous compounds.Amonafide is one of naphthalimide derivative carrying out the earliest clinical study, to human cervical carcinoma Hela, and human nasopharyngeal carcinoma KB and leukemia P388, HL-60 shows good restraining effect.Mitonafide has strong inhibition to human cervical carcinoma Hela and human nasopharyngeal carcinoma KB cell.Mitonafide is more similar with the Amonafide mechanism of action, is similarly DNA intercalator, and inducing DNA chain break under the intervention of type Ⅱ topoisomerase affects the normal physiological function of DNA, thereby reaches the effect of consistent cancer cell multiplication.Amonafide is in the clinical II phase at present, and clinical manifestation goes out myelosuppressive toxic side effect.Although the people such as Costanza report Amonafide, advanced breast cancer is had to therapeutic action, because its strong toxic side effect is had to end it and further studied.Mitonafide untoward reaction is clinically to cause larger nervus centralis toxicity, has stopped at present the clinical study of this compound.
Sulfur heterocyclic ring has important effect in the design of targeted molecular.Ott introduces mercaptobenzothiazole in naphthalimide, synthesize the naphthalimide derivative that a series of sulphur replaces, test shows that this series material Main Function is in topoisomerase I, or II type and have phototoxicity, and this has great significance in photodynamic therapy cancer.
Triazole class compounds can be by disturbing endothelial cell proliferation to suppress vasculogenesis, so be used for the assisting therapy of the diseases such as malignant hematologic disease, prostate cancer, kidney, lung cancer, neurospongioma as angiogenesis inhibitor.For example compd E 4896 is at present the clinical III phase and tests, and can be used for the treatment of mammary cancer, lung cancer, advanced ovarian cancer, kidney, in addition micromolecular lung cancer activity experiment result is shown: it can reduce by 51% vasculogenesis.
Summary of the invention
The object of the invention is with 4-bromo-1,8 naphthalene acid anhydrides are starting raw material, introduce five yuan of triazole rings and increase the conjugate area of naphthalimide parent in the mode of " non-naphtho-", connect active group mercaptobenzothiazole, the naphthalimide compound of a class containing 2-mercaptobenzothiazole and triazole heterocycle synthesized in design simultaneously.The diversity of expansion naphthalimide derivative, improves the biologic activity of molecule, thereby improves its antitumor performance.
The present invention solves the problems of the technologies described above adopted technical scheme: a class, containing the naphthalimide compound of 2-mercaptobenzothiazole and triazole heterocycle, is characterized in that described compound has the structure of general formula Y:
In general formula Y: be selected from-CH of R
2cH
2n (CH
3)
2,-CH
2cH
2n (CH
2cH
3)
2,-CH
2cH
2cH
2n (CH
3)
2,-CH
2cH
2n (CH
2cH
2)
2nH ,-CH
2cH
2oH ,-CH
2cH
2cH
3,-CH
2cH
2cH
2n (CH
2cH
3)
2or-CH
2cH
2cH
2cH
3.
Compound of the present invention is selected from:
N-(N ', N '-dimethyl amido ethyl)-6-(4-((benzothiazole-2-sulfydryl) methyl)-[1,2,3]-triazole) naphthalimide;
N-(N ', N '-diethyl amido ethyl)-6-(4-((benzothiazole-2-sulfydryl) methyl)-[1,2,3]-triazole) naphthalimide;
N-(N ', N '-dimethyl amido propyl group)-6-(4-((benzothiazole-2-sulfydryl) methyl)-[1,2,3]-triazole) naphthalimide;
N-(2 '-piperazinyl)-6-(4-((benzothiazole-2-sulfydryl) methyl)-[1,2,3]-triazole) naphthalimide;
N-(2 '-hydroxyethyl)-6-(4-((benzothiazole-2-sulfydryl) methyl)-[1,2,3]-triazole) naphthalimide;
Or N-butyl-6-(4-((benzothiazole-2-sulfydryl) methyl)-[1,2,3]-triazole) naphthalimide.
The preparation method of compound of the present invention, comprise the following steps: first with 4-bromo-1, 8 naphthalene acid anhydrides react to obtain intermediate 4-nitrine-1 with sodium azide, 8-naphthalimide, propargyl bromide reacts with 2-mercaptobenzothiazole and obtains intermediate 2-(2-alkynes-1-propyl dithiocarbamate) benzo [d] thiazole, two intermediates react and obtain 4-(4-((benzothiazole-2-sulfydryl) methyl)-[1 under sodium ascorbate and cupric sulfate pentahydrate catalysis, 2, 3]-triazole)-1, 8 naphthalene acid anhydrides, 4-(4-((benzothiazole-2-sulfydryl) methyl)-[1, 2, 3]-triazole)-1, 8 naphthalene acid anhydrides obtain described compound with corresponding amido hydrocarbon through amino condensation again.
Synthetic route is as follows:
Wherein, in the first step reaction, compound 1 (bromo-1, the 8 naphthalene acid anhydride of 4-) is 1:1.5 with the optimum mole ratio of sodium azide, taking DMF as solvent, obtain intermediate 2 (4-nitrine-1,8-naphthalimide) through azido reaction, cooling, filter, be dried to obtain yellow solid; In second step reaction, the optimum mole ratio of propargyl bromide and 2-mercaptobenzothiazole is 1:1, add again triethylamine (propargyl bromide: 2-mercaptobenzothiazole: triethylamine=1:1:1), after concussion, obtain intermediate 3 (2-(2-alkynes-1-propyl dithiocarbamate) benzo [d] thiazole) taking acetone as solvent supersonic, filter, distillation desolventizes, and obtains brown oily solid; In three-step reaction, intermediate 2 and intermediate 3, taking the trimethyl carbinol and water and mixed solution as solvent, add sodium ascorbate and cupric sulfate pentahydrate, through " the Click chemistry " of Cu (I) catalysis reaction, at N
2under protection, it is cooling that 70 DEG C of lucifuges reaction 24h obtains intermediate 4 (4-(4-((benzothiazole-2-sulfydryl) methyl)-[1,2,3]-triazole)-1,8 naphthalene acid anhydride), filters, the dry solid that to obtain; In four-step reaction, intermediate 4 reacts taking optimum mole ratio as 1:1.2 with corresponding amido hydrocarbon again, obtains compound of the present invention through amino condensation.
Compound of the present invention has the effect of inhibition tumor cell growth, and described tumour cell comprises MCF-7 breast cancer cell, Hela cervical cancer cell and SMMC-7721 liver cancer cell.
Compound of the present invention is carried out to the mensuration of extracorporeal suppression tumor cell growth activity to MCF-7 breast cancer cell, Hela cervical cancer cell and SMMC-7721 liver cancer cell by tetrazolium reduction method, result shows, this compounds has the activity that suppresses growth to the tumour cell of the multiple different tissue sources such as cervical cancer, liver cancer, mammary cancer.
Described tetrazolium reduction method experimental procedure is as follows:
1, inoculating cell
Respectively MCF-7 Breast Cancer Cell, human cervical carcinoma Hela cell and SMMC-7721 liver cancer cells are collected in substratum, 200 μ L cell suspensions are inoculated in every hole after cell dilution, ensure 2000～5000 cells of every Kong Zhongyue, outermost adds 200 μ LPBS, provide sufficient moisture to ensure the growing environment of cell, culture plate is put to 37 DEG C, 5%CO
2environment in incubation incubation 24h～48h.
2, add medicine
Compound of the present invention is diluted to respectively to 10 with substratum
-8, 10
-7, 10
-6, 10
-5tetra-gradient concentrations of M, suck the substratum that in 96 orifice plates, 2-11 is listed as, and are careful herein and do not siphon away cell; Then add medicine, 6 multiple holes are set, reduce error; After finishing dealing with, 96 orifice plates are put back to CO
2in incubator, cultivate 48h.
3, the detection of survivaling cell number
In institute is porose, all add 20 μ L MTT, be put into CO
2incubation 4h in incubator; Discard substratum and MTT in hole, add 200 μ L DMSO, dissolve residual MTT-formazan crystallization.In microplate reader, measure each hole absorbancy and record result, calculate the inhibiting rate of analyte to growth of cancer cells by following formula:
Tumor control rate=(control group OD value-treatment group OD value)/control group OD value × 100%
Beneficial effect of the present invention:
First, the present invention is at 4-bromo-1, on 8 naphthalene acid anhydride parents, introduce five yuan of triazole rings and increase the conjugate area of naphthalimide parent in the mode of " non-naphtho-", connect active group mercaptobenzothiazole, the naphthalimide compound of a class containing 2-mercaptobenzothiazole and triazole heterocycle synthesized in design simultaneously;
The second, the diversity of compound expansion naphthalimide derivative of the present invention, has improved the biologic activity of molecule, thereby has improved its antitumor performance.
Embodiment
Below by embodiment, the present invention is further illustrated, but do not limit the present invention in any way.
Embodiment 1
N-(N ', N '-dimethyl amido ethyl)-6-(4-((benzothiazole-2-sulfydryl) methyl)-[1,2,3]-triazole) naphthalimide (compound M1) synthetic:
(1) 4-nitrine-1.8-naphthalimide (intermediate 2)
In 50mL bottle with two necks, add bromo-1, the 8 naphthalene acid anhydride of 2.5g (9mmol) 4-, by 35mL DMF stirring and dissolving, 0.87g (13.5mmol) sodium azide is slowly added to reaction system, be heated to 55 DEG C, backflow lower magnetic force stirs 1h, cooling, reaction solution is poured into water, separate out a large amount of yellow mercury oxides, filter, dry, obtain 2.04g yellow solid, productive rate: 95.1%.
(2) 2-(2-alkynes-1-propyl dithiocarbamate) benzo [d] thiazole (intermediate 3)
Take 2-mercaptobenzothiazole 4.02g (24mmol) mercaptobenzothiazole, use 40mL acetone solution, add 3.34mL (24mmol) triethylamine, now reaction solution is orange transparent liquid, adds 1.88mL (24mmol) propargyl bromide, ultrasonic concussion 10 minutes, stopped reaction, filter, obtain brown filtrate, filtrate decompression distillation is removed to desolventizing.Obtain brown oily solid 4.82g, productive rate: 98.0%.Fusing point: 58.6-59.1 DEG C.
(3) 4-(4-((benzothiazole-2-sulfydryl) methyl)-[1,2,3]-triazole)-1,8 naphthalene acid anhydride (intermediate 4)
In 100mL bottle with two necks, add 2.40g (10mmol) 4-nitrine-1.8-naphthalimide, 2.05g (10mmol) intermediate 3, by the mixing solutions stirring and dissolving of the 1:1 of the 38mL trimethyl carbinol and water, add again catalyzer 5.94g sodium ascorbate (VC sodium) and 2.5g cupric sulfate pentahydrate, N
2under protection, at 70 DEG C of lucifuge reaction 24h, TLC tracks to and reacts completely.After reaction finishes, pour in cold water after system is cooled to room temperature, leave standstill, filter, dry.Obtain 4.41g intermediate 4, productive rate 99.3%.
(4) N-(N ', N '-dimethyl amido ethyl)-6-(4-((benzothiazole-2-sulfydryl) methyl)-[1,2,3]-triazole) naphthalimide (compound M1)
In 50mL bottle with two necks, add 1.5g (3.4mmol) compound 4-(4-((benzothiazole-2-sulfydryl) methyl)-[1,2,3]-triazole)-1,8 naphthalene acid anhydride, N, N-dimethyl-ethylenediamine 0.5mL (4.0mmol), 30mL dehydrated alcohol, stirs, reflux 3h, TLC tracks to and reacts completely.Reaction system is cooled to room temperature, pours in frozen water, suction filtration, washes with water, dry.(column chromatography elutriant is CH in silica gel column chromatography separation
2cl
2: CH
3oH=12:1), obtain target product 0.8g M1, filbert solid, productive rate 45.8%.Fusing point: 118.3-121.4 DEG C.
1H?NMR(400MHz,CDCl
3)δ8.65(dd,J＝7.3,4.0Hz,2H),8.18–8.06(m,2H),7.87(d,J＝8.0Hz,1H),7.78(dd,J＝10.8,4.1Hz,2H),7.68(dd,J＝8.4,7.5Hz,1H),7.47–7.38(m,1H),7.37–7.28(m,1H),4.85(s,2H),4.34(t,J＝6.3Hz,2H),2.69(s,2H),2.37(s,6H).
+ ESI MS (M+H): C
26h
22n
6o
2s
2, calculated value: 515.1246, measured value: 515.1310.
Embodiment 2
N-(N ', N '-diethyl amido ethyl)-6-(4-((benzothiazole-2-sulfydryl) methyl)-[1,2,3]-triazole) naphthalimide (compound M2) synthetic:
Except use N in (4), N-diethyl ethylenediamine replaces N, and outside N-dimethyl-ethylenediamine, other is synthetic and experiment treatment process is identical with embodiment 1.Through silica gel column chromatography separation, (column chromatography elutriant is CH
2cl
2: CH
3oH=12:1), obtain target product M2, filbert solid, productive rate 70.6%.Fusing point: 114.3-115.9 DEG C.
1H?NMR(400MHz,CDCl
3)δ8.66(dd,J＝7.4,4.1Hz,2H),8.16(s,1H),8.11(d,J＝8.6Hz,1H),7.88(d,J＝8.1Hz,1H),7.79(t,J＝7.8Hz,2H),7.69(t,J＝7.9Hz,1H),7.43(t,J＝7.6Hz,1H),7.33(t,J＝7.6Hz,1H),4.85(s,2H),4.35(t,J＝6.6Hz,2H),2.90(s,2H),2.77(s,4H),1.14(s,6H).
+ ESI MS (M+H): C
28h
26n
6o
2s
2, calculated value: 543.1559, measured value: 543.1635.
Embodiment 3
N-(N ', N '-dimethyl amido propyl group)-6-(4-((benzothiazole-2-sulfydryl) methyl)-[1,2,3]-triazole) naphthalimide (compound M3) synthetic:
Except use N in (4), N-dimethylated propyl diethylenetriamine replaces N, and outside N-dimethyl-ethylenediamine, other is synthetic and experiment treatment process is identical with embodiment 1.Through silica gel column chromatography separation, (column chromatography elutriant is CH
2cl
2: CH
3oH=12:1), obtain target product M3, filbert solid, productive rate 80.3%.Fusing point: 116.0-118.2 DEG C.
1H?NMR(400MHz,CDCl
3)δ8.66(dd,J＝7.4,4.7Hz,2H),8.16(s,1H),8.12(d,J＝8.5Hz,1H),7.88(d,J＝8.1Hz,1H),7.80(t,J＝8.5Hz,2H),7.74–7.62(m,1H),7.43(t,J＝7.6Hz,1H),7.33(t,J＝7.6Hz,1H),4.86(s,2H),4.27(t,J＝6.9Hz,2H),2.65(s,2H),2.42(s,6H),2.05(s,2H).
+ ESI MS (M+H): C
27h
24n
6o
2s
2, calculated value: 529.1402, measured value: 529.1462.
Embodiment 4
Synthesizing of N-(2 '-piperazinyl)-6-(4-((benzothiazole-2-sulfydryl) methyl)-[1,2,3]-triazole) naphthalimide (compound M4):
Except replace N with 1-(2-amino-ethyl) piperazine in (4), outside N-dimethyl-ethylenediamine, other is synthetic and experiment treatment process is identical with embodiment 1.Through silica gel column chromatography separation, (column chromatography elutriant is CH
2cl
2: CH
3oH: triethylamine=12:1:1), obtain target product M4, tawny solid, productive rate 75.7%.Fusing point: 143.5-144.6 DEG C.
1H?NMR(400MHz,CDCl3)δ8.66(dd,J＝7.3,4.0Hz,2H),8.15(s,1H),8.11(d,J＝8.0Hz,1H),7.88(d,J＝8.1Hz,1H),7.83–7.76(m,2H),7.72–7.66(m,1H),7.43(t,J＝7.2Hz,1H),7.33(t,J＝7.2Hz,1H),4.86(s,2H),4.34(t,J＝6.4Hz,2H),2.97(dd,J＝14.4,7.1Hz,5H),1.31(t,J＝7.3Hz,6H).
+ ESI MS (M+H): C
28h
25n
7o
2s
2, calculated value: 556.1511, measured value: 556.1572.
Embodiment 5
Synthesizing of N-(2 '-hydroxyethyl)-6-(4-((benzothiazole-2-sulfydryl) methyl)-[1,2,3]-triazole) naphthalimide (compound M5):
Except replace N with thanomin in (4), outside N-dimethyl-ethylenediamine, other is synthetic and experiment treatment process is identical with embodiment 1.Through silica gel column chromatography separation, (column chromatography elutriant is CH
2cl
2: CH
3oH=20:1), obtain target product M5, light orange solids, productive rate 83.2%.Fusing point: 120.1-122.7 DEG C.
1H?NMR(400MHz,CDCl3)δ8.76–8.63(m,2H),8.20–8.11(m,2H),7.88(d,J＝8.1Hz,1H),7.81(dd,J＝12.2,7.9Hz,2H),7.71(dd,J＝8.5,7.4Hz,1H),7.47–7.39(m,1H),7.34(dd,J＝11.2,4.1Hz,1H),5.30(s,1H),4.86(s,2H),4.48(t,J＝5.3Hz,2H),4.00(t,J＝5.3Hz,2H).
13C?NMR(101MHz,CDCl3)δ164.46,163.91,152.90,138.23,132.49,130.98,129.59,129.09,128.62,126.30,126.23,124.64,123.61,122.69,121.46,121.27,61.49,53.46,42.95,27.45.
+ ESI MS (M+H): C
24h
17n
5o
3s
2, calculated value: 488.0733, measured value: 488.0836.
Embodiment 6
Synthesizing of N-butyl-6-(4-((benzothiazole-2-sulfydryl) methyl)-[1,2,3]-triazole) naphthalimide (compound M6):
Except replace N with n-Butyl Amine 99 in (4), outside N-dimethyl-ethylenediamine, other is synthetic and experiment treatment process is identical with embodiment 1.Through silica gel column chromatography separation, (column chromatography elutriant is CH
2cl
2: CH
3oH=10:1), obtain target product M6, light orange solids, productive rate 85.9%.Fusing point: 146.8-148.3 DEG C.
1H?NMR(400MHz,CDCl3)δ8.71–8.64(m,2H),8.14(s,1H),8.10(dd,J＝8.6,0.9Hz,1H),7.88(d,J＝8.0Hz,1H),7.80(t,J＝7.5Hz,2H),7.69(dd,J＝8.5,7.4Hz,1H),7.48–7.39(m,1H),7.38–7.29(m,1H),4.85(s,2H),4.24–4.14(m,2H),1.73(ddd,J＝12.7,8.6,6.6Hz,2H),1.46(dd,J＝15.2,7.5Hz,2H),0.99(t,J＝7.3Hz,3H).
+ ESI MS (M+H): C
26h
21n
5o
2s
2, calculated value: 500.1137, measured value: 500.1193.
Application examples
Extracorporeal suppression tumor cell growth activity is measured:
MCF-7 breast cancer cell, Hela cervical cancer cell and SMMC-7721 liver cancer cell are carried out to extracorporeal suppression tumor cell growth activity mensuration by tetrazolium (microculture tetrozolium, MTT) reduction method.
Taking compound M1 as example, the concrete operations of tetrazolium (MTT) reduction method are:
1, inoculating cell
Some amount is collected in substratum in the tumour cell of logarithmic phase, every hole inoculation after cell dilution is added to 200 μ L cell suspensions, approximately 2000～5000 cells, outermost adds 200 μ L PBS, provide sufficient moisture to ensure the growing environment of cell, culture plate is put to 37 DEG C, 5%CO
2incubation 24h in the incubator of environment.
2, add medicine
The compound M1 with substratum being prepared by embodiment 1 is diluted to respectively 10
-8, 10
-7, 10
-6, 10
-5tetra-gradient concentrations of M; Suck the substratum of 2-11 row in 96 orifice plates, be careful herein and do not siphon away cell, then add medicine, each concentration arranges 6 multiple holes, reduces error; After finishing dealing with, 96 orifice plates are put back to CO
2in incubator, cultivate 48h.
3, the detection of survivaling cell number
In institute is porose, all add 20 μ L MTT, be put into CO
2incubation 4h in incubator; Discard substratum and MTT in hole, add 200 μ L DMSO, lysigenous crystallization.In microplate reader, measure each hole absorbancy and record result, calculate the inhibiting rate of analyte to growth of cancer cells by following formula:
Tumor control rate=(control group OD value-treatment group OD value)/control group OD value × 100%.
The detection method of compound M2～M6 is the same.
According to the tumor control rate of compound M1～M6, calculate its IC
50value, result is as following table:
The IC of table 1. compound M1～M6 to Hela, MCF-7 and 7721 cancer cells
50value
Can data analysis can prove from table 1: six synthetic compound M1-M6 have obvious inhibition proliferation function to three kinds of tumour cells, two nitrogen-atoms of this series compound side chain are significantly active every the inhibition of two carbon compound M1, and the IC50 value of MCF-7, Hela and 7721 is respectively to 2.33 μ M, 0.35 μ M, 0.49 μ M.The selectivity to MCF-7 and Hela of M3, M4 is better than 7721 cells, and M3, the M4 IC to MCF-7, Hela cell
50value is respectively 0.35 μ M, 0.12 μ M and 0.66 μ M, 0.19 μ M.
Claims (5)
1. a class, containing the naphthalimide compound of 2-mercaptobenzothiazole and triazole heterocycle, is characterized in that described compound has the structure of general formula Y:
In general formula Y: be selected from-CH of R
2cH
2n (CH
3)
2,-CH
2cH
2n (CH
2cH
3)
2,-CH
2cH
2cH
2n (CH
3)
2,-CH
2cH
2n (CH
2cH
2)
2nH ,-CH
2cH
2oH ,-CH
2cH
2cH
3,-CH
2cH
2cH
2n (CH
2cH
3)
2or-CH
2cH
2cH
2cH
3.
2. compound according to claim 1, is characterized in that described compound is selected from:
N-(N ', N '-dimethyl amido ethyl)-6-(4-((benzothiazole-2-sulfydryl) methyl)-[1,2,3]-triazole) naphthalimide;
N-(N ', N '-diethyl amido ethyl)-6-(4-((benzothiazole-2-sulfydryl) methyl)-[1,2,3]-triazole) naphthalimide;
N-(N ', N '-dimethyl amido propyl group)-6-(4-((benzothiazole-2-sulfydryl) methyl)-[1,2,3]-triazole) naphthalimide;
N-(2 '-piperazinyl)-6-(4-((benzothiazole-2-sulfydryl) methyl)-[1,2,3]-triazole) naphthalimide;
N-(2 '-hydroxyethyl)-6-(4-((benzothiazole-2-sulfydryl) methyl)-[1,2,3]-triazole) naphthalimide;
Or N-butyl-6-(4-((benzothiazole-2-sulfydryl) methyl)-[1,2,3]-triazole) naphthalimide.
3. the preparation method of compound described in claim 1 or 2, comprise the following steps: first with 4-bromo-1, 8 naphthalene acid anhydrides react to obtain intermediate 4-nitrine-1 with sodium azide, 8-naphthalimide, propargyl bromide reacts with 2-mercaptobenzothiazole and obtains intermediate 2-(2-alkynes-1-propyl dithiocarbamate) benzo [d] thiazole, two intermediates react and obtain 4-(4-((benzothiazole-2-sulfydryl) methyl)-[1 under sodium ascorbate and cupric sulfate pentahydrate catalysis, 2, 3]-triazole)-1, 8 naphthalene acid anhydrides, 4-(4-((benzothiazole-2-sulfydryl) methyl)-[1, 2, 3]-triazole)-1, 8 naphthalene acid anhydrides obtain described compound with corresponding amido hydrocarbon through amino condensation again.
4. the application of the compound described in claim 1 or 2 in inhibition tumor cell growth.
5. application according to claim 4, is characterized in that described tumour cell comprises MCF-7 breast cancer cell, Hela cervical cancer cell and SMMC-7721 liver cancer cell.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410246653.8A CN104072493B (en) | 2014-06-05 | 2014-06-05 | One class contains 2-mercaptobenzothiazole and the naphthalimide compound of triazole heterocycle, its preparation method and application thereof |
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|---|---|---|---|
| CN201410246653.8A CN104072493B (en) | 2014-06-05 | 2014-06-05 | One class contains 2-mercaptobenzothiazole and the naphthalimide compound of triazole heterocycle, its preparation method and application thereof |
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| CN105130895A (en) * | 2015-08-04 | 2015-12-09 | 大连理工大学 | Naphthalimide derivatives, preparation method and applications thereof |
| CN105130896A (en) * | 2015-08-04 | 2015-12-09 | 大连理工大学 | Naphthalimide derivatives containing thiourea substituent, preparation method and applications thereof |
| CN108570044A (en) * | 2018-07-02 | 2018-09-25 | 秦继伟 | A kind of purposes of amides compound and its synthetic method and treating cancer |
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| CN108892664A (en) * | 2018-07-02 | 2018-11-27 | 秦继伟 | A kind of purposes of amides compound and its synthetic method and treating cancer |
| CN108912115A (en) * | 2018-07-02 | 2018-11-30 | 秦继伟 | It is a kind of for treating the EGFR tyrosine kinase inhibitor of lung cancer |
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105130895A (en) * | 2015-08-04 | 2015-12-09 | 大连理工大学 | Naphthalimide derivatives, preparation method and applications thereof |
| CN105130896A (en) * | 2015-08-04 | 2015-12-09 | 大连理工大学 | Naphthalimide derivatives containing thiourea substituent, preparation method and applications thereof |
| CN105130896B (en) * | 2015-08-04 | 2017-11-10 | 大连理工大学 | The naphthalimide derivative of a kind of substituent containing thiocarbamide, its preparation method and application |
| CN108570044A (en) * | 2018-07-02 | 2018-09-25 | 秦继伟 | A kind of purposes of amides compound and its synthetic method and treating cancer |
| CN108690013A (en) * | 2018-07-02 | 2018-10-23 | 秦继伟 | Ben Bing [d]Thiazole and its application as EGFR inhibitor in treatment of cancer |
| CN108892664A (en) * | 2018-07-02 | 2018-11-27 | 秦继伟 | A kind of purposes of amides compound and its synthetic method and treating cancer |
| CN108912115A (en) * | 2018-07-02 | 2018-11-30 | 秦继伟 | It is a kind of for treating the EGFR tyrosine kinase inhibitor of lung cancer |
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