CN106946888B - A kind of sulfoamido derivative and its purposes in antitumor drug is prepared - Google Patents

Abstract

The invention discloses a kind of sulfoamido derivative formulas（Ⅰ）And its purposes in antitumor drug is prepared,Wherein, R is (CH₂)_nCH₃, n=0 ~ 6.

Description

A kind of sulfoamido derivative and its purposes in antitumor drug is prepared

Technical field

The present invention relates to a kind of sulfoamido derivative formulas（Ⅰ）And its purposes in antitumor drug is prepared, especially relate to And a kind of sulfoamido derivative formula（Ⅰ）In liver cancer, lung cancer, glioma, stomach cancer, oophoroma, breast cancer, leukaemia Using.

Background technology

Cancer is the great subject under discussion of life science, and the life quality that malignant tumour serious threat the mankind is good for as the mankind First killer of health.The mankind are constantly carrying out the research of antitumor drug always for many years, find new and effective, less toxic resist Tumour medicine is always the hot spot of medicine research and development both at home and abroad.The screening of antitumor drug is all paid much attention in countries in the world, input Substantial amounts of human and material resources, financial resources, there is a substantial amounts of compound every year（Chemical synthesis, natural products and microbial fermentation production Object）By screening anti-tumor medicine.Micromolecular compound has critical role in tumour research and development.It is annual to have largely small point Sub- chemical entities are devised and carry out the screening active ingredients of different adaptation disease drugs, but due to designing the initial of compound The difference of purpose and designer's research interest, the exploitation of many compounds is not comprehensive, and many outstanding pharmacological effect functions are not It can be developed, on the other hand, since newly-designed compound is generally all protected in the form of compound patent, more extensively For the exploitation of general ground purposes for non-patentee there are patent barrier, commercial value is low.

The content of the invention

It is an object of the invention to provide a kind of sulfoamido derivative formulas（Ⅰ）And its use in antitumor drug is prepared On the way more particularly to a kind of sulfoamido derivative formula（Ⅰ）Liver cancer, lung cancer, glioma, stomach cancer, oophoroma, breast cancer, Application in leukaemia.Sulfoamido derivative formula（Ⅰ）

Wherein, R is-(CH₂)_nCH₃, n=0 ~ 6.

Further, formula（Ⅰ）The compound of expression, its salt or its solvated compounds.

Further, formula（Ⅰ）Synthetic route be

。

Further, formula（Ⅰ）Purposes in antitumor drug is prepared.

Further, the tumour is malignant tumour, and the malignant tumour is solid tumor or non-physical knurl.

Preferably, the solid tumor for liver cancer, lung cancer, glioma, stomach cancer, oophoroma, breast cancer, the non-physical Knurl is leukaemia.

A kind of anti-tumor compositions, which is characterized in that including sulfoamido derivative formula described in claim 1（Ⅰ）And Medically acceptable auxiliary material.

The present invention is not to sulfoamido derivative formula（Ⅰ）Or include sulfoamido derivative formula（Ⅰ）Composition apply It is particularly limited with mode, representative method of application includes（But it is not limited to）：Oral, parenteral（Intravenously, intramuscular It is or subcutaneous）And local administration.Include capsule, tablet, pill, powder and granule for the solid dosage forms of oral medication. In these solid dosage forms, sulfoamido derivative formula（Ⅰ）With at least one conventional inert excipients（Or carrier）Mixing, such as lemon Sour sodium or Dicalcium Phosphate are mixed with following compositions：（a）Filler or bulking agent, for example, it is starch, lactose, sucrose, glucose, sweet Reveal alcohol and silicic acid；（b）Adhesive, for example, hydroxymethyl cellulose, alginates, gelatin, polyvinylpyrrolidone, sucrose and I Primary glue；（c）Moisturizer, such as glycerine；（d）Disintegrant, for example, agar, calcium carbonate, potato starch or tapioca, alginic acid, Some composition silicates, sodium carbonate；（e）Retarding solvent, such as paraffin；（f）Absorbsion accelerator, such as quaternary ammonium compound；（g）Wetting Agent, such as cetanol and glycerin monostearate；（h）Adsorbent, such as kaolin；（i）Lubricant, such as talcum, stearic acid Calcium, magnesium stearate, solid polyethylene glycol, lauryl sodium sulfate.In capsule, tablet and pill, dosage form can also include buffering Agent.

Wherein, gastrointestinal administration preparation is presently the most common administration form, and convenient experimental operation, therefore, this hair Sulfoamido derivative formula is carried out using gastric infusion in bright specific embodiment（Ⅰ）The test of pesticide effectiveness, it is not intended that, sulphur Amido derivatives formula（Ⅰ）Antitumor administration form is only limitted to gastrointestinal administration, and those skilled in the art can be according to sulphonyl Amido derivative formula（Ⅰ）Physicochemical properties, with reference to Modern preparations technology and the actual needs of sufferer, be prepared into injecting The several formulations such as agent, scalp absorbable preparation, implantation preparation so as to expand its administration route, and improve target-oriented drug or effective Avoid unnecessary toxic side effect.

Liquid formulation for oral administration includes pharmaceutically acceptable lotion, solution, suspension, syrup or tincture. Except active ingredient beyond the region of objective existence, liquid dosage form can include the inert diluent routinely used in this field, such as water or other solvents, increase Solvent and emulsifier, example know ethyl alcohol, isopropanol, ethyl carbonate, ethyl acetate, propylene glycol, 1,3-BDO, dimethylformamide And oil, the particularly mixture of cottonseed oil, peanut oil, maize germ, olive oil, castor oil and sesame oil or these substances Deng.

In addition to these inert diluents, composition can also include auxiliary agent, such as wetting agent, emulsifier and suspending agent, sweet taste Agent, corrigent and fragrance.

Except active ingredient beyond the region of objective existence, suspension can include suspending agent, such as ethoxylation isooctadecane alcohol, polyoxyethylene mountain Pears alcohol and the mixture of Isosorbide Dinitrate, microcrystalline cellulose, aluminium methoxide and agar or these substances etc..

For parenteral injection composition can include physiologically acceptable sterile, aqueous or anhydrous solution, dispersion liquid, Suspension or lotion with for re-dissolving into the aseptic powdery of sterile Injectable solution or dispersion liquid.It is suitable aqueous and Nonaqueous carrier, diluent, solvent or excipient include water, ethyl alcohol, polyalcohol and its suitable mixture.

Dosage form for the compounds of this invention of local administration includes ointment, powder, patch, propellant and inhalant. Active ingredient aseptically with that physiologically acceptable carrier and any preservative, buffer or may need if necessary Propellant be mixed together.

The compounds of this invention can be administered alone or with other pharmaceutically acceptable other drugs administering drug combinations.

Obviously, the above according to the present invention according to the ordinary technical knowledge and means of this field, is not departing from this hair Under the premise of bright above-mentioned basic fundamental thought, the modification, replacement or change of other diversified forms can also be made.

Specific embodiment

Embodiment 1

The synthesis of 5- [2- methyl -7H- (2,3-d) pyrrolo-pyrimidine radicals -4- sulfoamidos] furyl -2- formyl chlorides

Under the conditions of the aqueous solution (17.5 mmol) of 5- amino furan base -2- formyl chlorides is placed in ice-water bath, then by 2- first Base -7H-（2,3-d）Pyrrolo-pyrimidine radicals -4- sulfonic acid chlorides（10 mmol）It is added dropwise in above-mentioned system, internal temperature during being added dropwise Degree control between 20-24 °C, after being added dropwise, remove ice-water bath, when stirring at normal temperature 10 is small after, add in NaCl (4 g), continue Stir 1 it is small when.It is extracted with dichloromethane (200 mL, 100 mL x 2), organic phase anhydrous Na₂SO₄It is dry, solvent evaporated Afterwards, with acetone and ethyl alcohol（3:1）Recrystallization, obtains 3 g 5- [2- methyl -7H- (2,3-d) pyrrolo-pyrimidine radicals -4- sulfoamidos] Furyl -2- formyl chlorides, yield 88% are white solid powder.¹H-NMR (400 MHz, CDCl₃) δ: 2.18(s, 3H), 7.12(d, 1H), 7.37(m, 2H), 7.72(d, 1H), 7.90(s, 1H), 9.48(s, 1H); ¹³C-NMR (75 MHz, CDCl₃) δ: 25.37, 100.83, 101.36, 120.08, 124.61, 126.61, 145.33, 153.14, 154.91, 155.40, 157.73, 159.40

Wherein, 2- methyl -7H-（2,3-d）Pyrrolo-pyrimidine radicals -4- sulfonic acid chlorides

¹H-NMR (400 MHz, CDCl3) δ:2.18(s,3H), 7.11(d,1H), 7.35(d,1H),7.89(s, 1H).

2- methyl-N-2- [5- (morpholinyl -4- carbonyls) furyl] -7H- (2,3-d) pyrrolo-pyrimidine radicals -4- sulfonamide Synthesis

Triethylamine is added in into 5- [2- methyl -7H- (2,3-d) pyrrolo-pyrimidine radicals -4- sulfoamidos] furyl -2- formyls Chlorine（10mmol）Dichloromethane solution in, the dichloromethane solution of morpholine (12 mmol) is added dropwise in system, is stirred at room temperature 16 it is small when.With 5% aqueous sodium carbonate washing reaction system, organic phase anhydrous Na₂SO₄It is dry, after solvent evaporated, obtain Solid flash column chromatography separates, and obtains 3.4 g 2- methyl-N-2- [5- (morpholinyl -4- carbonyls) furyl] -7H- (2,3-d) Pyrrolo-pyrimidine radicals -4- sulfonamide, yield 86.9% are pale yellow powder.¹H-NMR (400 MHz, CDCl₃) δ: 2.21 (s, 3H), 3.51(m, 4H), 3.61(m, 4H), 7.16(dd, 2H), 7.42(dd, 2H), 7.93(s, 1H), 9.25(s, 1H); ¹³C-NMR (75 MHz, CDCl₃) δ:25.37, 44.83, 66.36, 100.83, 101.36, 115.51, 120.08,126.61,151.81,154.91,155.40,157.73,159.40,160.39.

The synthesis of 2- methyl-N-2- [5- (morpholine methyl) furyl] -7H- (2,3-d) pyrrolo-pyrimidine radicals -4- sulfonamide

With methanol and tetrahydrofuran（2:1）Mixed solvent dissolves 2- methyl-N-2- [5- (morpholinyl -4- carbonyls) furans Base] -7H- (2,3-d) pyrrolo-pyrimidine radicals -4- sulfonamide (10 mmol), sodium borohydride is added in thereto under the conditions of ice-water bath, Stirring half an hour recession remove ice-water bath, be stirred at room temperature 1 it is small when, then thereto add in 200 milliliters of water, filtering, obtained solid warp Quick pillar layer separation is crossed, obtains 3.2 g 2- methyl-N-2- [5- (morpholine methyl) furyl] -7H- (2,3-d) Pyrrolopyrimidin Piperidinyl -4- sulfonamide, yield 84.8%, micro-yellow powder.¹H-NMR (400 MHz, CDCl₃) δ: 2.17(s, 3H), 2.41(t, 4H), 3.56(t, 3H), 3.75(s, 2H), 6.11(d, 1H), 6.92(d, 1H), 7.07(d, 1H), 7.34(d, 1H), 7.89(s, 1H), 9.47(s, 1H); ¹³C-NMR (75 MHz, CDCl₃) δ: 25.37, 52.68, 55.18, 67.08, 96.87, 99.50, 100.83, 120.08, 126.61, 148.35, 154.91, 155.40, 156.75, 159.40.m/z: 377.12 (100.0%), 378.2 (18.5%).

Embodiment 2

The synthesis of 5- [2- amyls -7H- (2,3-d) pyrrolo-pyrimidine radicals -4- sulfoamidos] furyl -2- formyl chlorides

Under the conditions of the aqueous solution (17.5 mmol) of 5- amino furan base -2- formyl chlorides is placed in ice-water bath, then by 2- penta Base -7H-（2,3-d）Pyrrolo-pyrimidine radicals -4- sulfonic acid chlorides（10 mmol）It is added dropwise in above-mentioned system, internal temperature during being added dropwise Degree control at 15 °C or so, after being added dropwise, remove ice-water bath, when stirring at normal temperature 20 is small after, add in 20ml saturated salt solutions, after When continuous stirring 1 is small.It is extracted with dichloromethane (200 mL, 100 mL x 2), organic phase anhydrous Na₂SO₄It is dry, solvent evaporated Afterwards, with acetone and ethyl alcohol（3:1）Recrystallization, obtains 3.6 g 5- [2- amyls -7H- (2,3-d) pyrrolo-pyrimidine radicals -4- sulfonamide Base] furyl -2- formyl chlorides, yield 91% is white solid powder.¹H-NMR (400 MHz, CDCl₃) δ: 0.91(m, 3H), 1.35(m,4H), 1.59(m,2H), 2.86(t,2H), 7.19(d,1H), 7.38(t,2H), 7.73(d,1H), 7.92(s,1H), 9.06(s,1H); ¹³C-NMR (75 MHz, CDCl₃) δ:14.00, 23.16, 23.97,30.73, 36.42, 100.83, 101.36, 117.48, 124.61, 126.61, 145.33, 153.14, 154.17, 157.73, 158.92, 163.15.

2- amyls-N-2- [5- (morpholinyl -4- carbonyls) furyl] -7H- (2,3-d) pyrrolo-pyrimidine radicals -4- sulfonamide Synthesis

By 5- [2- amyls -7H- (2,3-d) pyrrolo-pyrimidine radicals -4- sulfoamidos] furyl -2- formyl chlorides（10mmol） It is dissolved in 100 ml dichloromethane solutions, adds in 1ml triethylamines thereto, the dichloromethane solution of morpholine (12 mmol) is dripped In addition system, be stirred at room temperature 10 it is small when.With the aqueous sodium carbonate washing reaction system of 100 ml 5%, organic phase is with anhydrous Na₂SO₄It is dry, after solvent evaporated, obtained solid flash column chromatography separation, obtain 4 g 2- amyls-N-2- [5- (morpholinyl- 4- carbonyls) furyl] -7H- (2,3-d) pyrrolo-pyrimidine radicals -4- sulfonamide, yield 89% is pale yellow powder.¹H-NMR (400 MHz, CDCl3) δ: 0.91(m,3H), 1.35(m,4H), 1.59(m,2H), 2.87(t,2H), 3.51(m, 4H), 3.61(m,4H), 7.15(d,1H), 7.20(d,1H), 7.38(d,1H), 7.44(d,1H), 7.93(s,1H), 9.19(s,1H); ¹³C-NMR (75 MHz, CDCl3) δ: 14.02, 23.16, 23.97, 30.73, 36.42, 44.83, 66.36, 100.83, 101.36, 115.51, 117.48, 126.61, 151.81, 154.17, 157.73, 158.92, 160.39, 163.15. m/z: 447.16 (100.0%), 448.16 (22.9%), 449.15 (4.5%) .

The synthesis of 2- amyls-N-2- [5- (morpholine methyl) furyl] -7H- (2,3-d) pyrrolo-pyrimidine radicals -4- sulfonamide

With methanol and tetrahydrofuran（1:1）Mixed solvent dissolving 5- [2- amyls -7H- (2,3-d) pyrrolo-pyrimidine radicals -4- Sulfoamido] furyl -2- formyl chlorides (10 mmol), sodium borohydride is added in thereto under the conditions of ice-water bath, is maintained temperature below 5 DEG C, stirring half an hour recession remove ice-water bath, be stirred at room temperature 1 it is small when, then add in 200 ml water thereto, filter, obtained solid It is separated by flash column chromatography, obtains 3.8 g 2- amyls-N-2- [5- (morpholine methyl) furyl] -7H- (2,3-d) pyrrolo- Pyrimidine radicals -4- sulfonamide, yield 88%, off-white powder.¹H-NMR (400 MHz, CDCl₃) δ: 0.91(m,3H), 1.34 (m,4H), 1.58(m,2H), 2.41(t,4H), 2.86(t,2H), 3.56(t,4H), 3.74(s,2H), 6.10(d, 1H), 6.91(d,1H), 6.99(d,1H), 7.34(d,1H), 7.89(s,1H), 9.48(s,1H); ¹³C-NMR (75 MHz, CDCl₃) δ: 14.00, 23.16, 23.97, 30.73, 36.42, 52.68, 55.18, 67.08, 96.87, 99.50, 100.83, 117.48, 126.61, 148.35, 154.17, 156.75, 158.92, 163.15. m/z: 433.18 (100.0%), 434.18 (24.7%), 435.17 (4.5%).

Test example 1：MTT（Tetrazolium bromide）Method measures sulfoamido derivative formula（Ⅰ）To the inhibitory action of different tumour cells.

First, cell line

Human lung cancer cell A549, human liver cancer cells Hep G2, Human hepatoma cell line Bel-7402, neuroglia cell of human Oncocyte U251, human large cell lung cancer cell NCI-H460, human gastric adenocarcinoma BGC-823, human gastric adenocarcinoma SGC-7901, People ovary adenocarcinoma cells SK-OV-3, human breast cancer cell line Bcap-37, people's chronic myelogenous leukemia cell K562.

2nd, main solution is prepared：

1.PBS buffer solutions：

NaCl 8g、KCl 0.2g、Na₂HPO₄ 1.44g、KH₂PO₄0.24g adjusts ph 7.4, constant volume 1L.

2. trypsin solution：

0.25% trypsase+0.02%EDTA, is prepared with PBS buffer solution, and 0.22 μm of membrane filtration degerming, 4 DEG C spare.

1640 cell culture fluids of 3.RPMI：

（1）The culture powder of 10.4g/ bags RPMI 1640 is molten into tri-distilled water, magnetic agitation 20min；

（2）Add 2g NaHCO₃, continue to stir 10min；

（3）Add penicillin solution（2×10⁵U/mL）0.5mL, Streptomycin Solution（2× 10⁵U/mL）0.5mL；

（4）Add 100ml inactivated fetal bovine serums；

（5）Add 1mol/L HCl, adjust PH to 7.2, constant volume 1L；

（6）Filtration sterilization.

4. test medicine gradient solution：

（1）Sulfoamido derivative formula（Ⅰ）Gradient solution：Sulfoamido derivative formula（Ⅰ）After being dissolved with a small amount of DMSO（Most Whole DMSO contents are within 0.1%）, be configured to 128 μ g/ml with 1640 cell culture fluids of RPMI, half-and-half dilution be configured to 8 it is dense Gradient is spent, i.e.,：64th, 32,16,8,4,2,1,0.5 μ g/ml, with preceding preparation.

（2）Cis-platinum gradient solution：Cisplatin injections are configured to 128 μ g/ml with 1640 cell culture fluids of RPMI, half-and-half dilute It releases and is configured to 8 concentration gradients, i.e., 128,64,32,16,8,4,2,1 μ g/ml, with preceding preparation.

3rd, experiment packet：

Medicine group to be measured（Referring to experimental procedure part）

Positive control medicine group（Compared with drug test group, the drug to be measured for adding in concentration gradient is changed to add in concentration ladder The cis-platinum of degree）

Control group（Compared with drug test group, the drug to be measured for adding in concentration gradient is changed to add in the RPMI of not drug containing 1640 cell culture fluids）

Blank group（Compared with the control group, it is not added with cell）

4th, experimental procedure：

1. the cell in growth period of taking the logarithm, Trypsin Induced, 1640 cell culture fluid tune concentration of cell suspension of RPMI are 6×10⁴A/mL.Add 100 μ L of cell suspension per hole in 96 well culture plates, put 37 DEG C, 5% CO₂It is cultivated in incubator for 24 hours, carefully Born of the same parents are adherent.

2. removing 1640 cell culture fluids of RPMI, 1640 cell culture fluids of RPMI of the drug to be measured of concentration gradient are added in 100 μ L, each concentration set 6 parallel holes.96 orifice plates after dosing are placed in 37 DEG C, 5% CO₂48h is cultivated in incubator, is inverted The effect of micro- Microscopic observation drug.

Culture solution is discarded after the centrifugation of 3.96 orifice plates, after carefully being rushed 2 ~ 3 times with PBS, adds the RPMI containing 0.5% MTT 1640 cell culture fluid, 100 μ L continue to cultivate 4h.

4. removing supernatant, 150 μ L dimethyl sulfoxide (DMSO)s are added in per hole, low-speed oscillation 10min on shaking table is put, ties formazan Brilliant fully dissolving.

5. the optical density in each hole is measured at enzyme-linked immunosorbent assay instrument 490nm（OD values）.

6. parallel hole OD values are represented with mean ± SD, inhibiting rate formula is calculated：[(OD_{Control group}-OD_{Blank group})-(OD_{Drug study group}- OD_{Blank group})]/(OD_{Control group}-OD_{Blank group})*100%。

7. using 5 data processing softwares of GraphPad Prism, by drawing amount effect curve calculation of half inhibitory concentration （IC₅₀）.

5th, experimental result

Sulfoamido derivative formula（Ⅰ）There are different degrees of In-vitro Inhibitory Effect, IC to 10 kinds of human tumor cell lines₅₀ （It is shown in Table 1）.Compared with positive drug cis-platinum, sulfoamido derivative formula（Ⅰ）Different structure is to different people inhibiting tumour cells journey Spend difference, sulfoamido derivative formula（Ⅰ）There is also difference between different structure.Sulfoamido derivative formula as a result,（Ⅰ） Can be used for preparing antitumor drug, tumour is malignant tumour, including solid tumor or non-physical knurl, wherein solid tumor be liver cancer, Lung cancer, glioma, stomach cancer, oophoroma, breast cancer, non-physical knurl are leukaemia.

Test example 2：Bel-7402 transplanted human hepatocellular carcinomas mouse model is studied

First, human liver cancer nude mouse xenotransplant cancer model is established

SPF grades of Balb/c nude mices, male, 4 week old, people's Bel-7402 liver cancer cells nude mice models of learning from else's experience are into knurl, then through naked Mouse passes on 2 tumor mass more than generation, is cut into about 2*2*2mm, and it is subcutaneous to be inoculated in nude mice armpit using trochar, establishes human liver cancer nude mice Heteroplastic transplantation cancer model.

2nd, dosage regimen

With the length and width of each animal knurl of vernier caliper measurement, by formula：V=1/2*ab²Knurl volume is calculated, treats knurl volume It grows to about 100mm³Start to be administered, all animals are randomly divided into model group, positive drug capecitabine group by knurl volume（400mg/ kg）, formula（Ⅰ）Group（100mg/kg）, every group 8, each group gastric infusion, dosage is l0ml/kg, 1 time/d, successive administration 14d.

3rd, knurl weight and tumour inhibiting rate

Tumor mass is stripped, assay balance claims knurl weight, calculates tumour inhibiting rate as follows.

Tumour inhibiting rate %=（Model group knurl weight-the administration group that is averaged is averaged knurl weight）/ model group is averaged knurl weight * 100%.

Compared with model group, capecitabine group and three compound Bel-7402 transplanted human hepatocellular carcinomas that number is a, c, e are small Mouse knurl weight has decline, and three compound tumour inhibiting rates of number a, c, e are above capecitabine group.Number is the three of a, c, e A compound Bel-7402 transplanted human hepatocellular carcinoma mouse knurl weights and tumour inhibiting rate are shown in Table 2.

Studies show that, the medication effect of nude mice model tumor model and clinical treatment has apparent correlation, it can Preferably to forecast the clinical efficacy of drug.It is possible thereby to deduce, formula（Ⅰ）Antitumor drug application can be used as.

Test example 3：People's renal epithelial cell（293T）Toxicity research

The present invention tests sulfoamido derivative formula（Ⅰ）To people's renal epithelial cell（293T）Cytotoxicity, cell toxicant Property result such as table 3, using celecoxib as positive control.The toxicity of each compound is used when inhibiting T cell survival rate to 50% Concentration（CC₅₀）To represent.

First, experimental method

(1) people's renal epithelial cell is cultivated（293T）Until reaching its logarithmic growth end of term cell tends to merge, disappeared with cell Change liquid digestion cell dispersion, 1 × 10 is configured to cell culture fluid⁴The cell suspension of a/mL.96 well culture plates are taken, in every hole Add in the cell suspension of 100 μ L.Gently horizontally rotate the surface that culture plate makes cell be evenly dispersed in ware hole.

(2) it is placed in containing 5%CO₂In cell incubator, cultivated for 24 hours at a temperature of 37 ± 2 DEG C.Original fluid is discarded, per hole Add in the blank control liquid of 100 μ L, negative controls, positive control solution, the test specimen leaching liquor of 100% and 50% concentration.Often Group at least sets 8 holes.Note：Extraction stoste or the series extraction dilution for making diluent with culture medium.Using 0.9% chloride injection When liquid extracts, 2 times of culture mediums of concentration are used when diluting extraction.

(3) it is placed in containing 5% CO₂In incubator, cultivated at a temperature of 37 ± 2 DEG C.Cultivate 48h.

(4) 20 μ L of MTT solution are added in per hole, are placed in containing 5% CO after the phase between each culture₂In incubator, at 37 ± 2 DEG C At a temperature of cultivate 5h.

(5) liquid in hole is discarded, 200 μ L DMSO is separately added into per hole, culture plate is placed into 10min, level, which is rocked, makes hole Interior solution colour is uniform.

(6) absorbance is measured with microplate reader, wavelength uses 570nm.The CC measured₅₀It is shown in Table 3.

3 formula of table（Ⅰ）To the inhibition CC of 293T cells₅₀It is worth (μm ol/mL)

Number	CC50(μmol/mL)
		Celecoxib	55.22
a	60.38
		b	58.32
c	58.48
		d	62.52
e	62.21
		f	64.61
g	63.88

Sulfoamido derivative formula of the present invention（Ⅰ）Seven structures to people's renal epithelial cell（293T）Show quite or Person is better than the cytotoxicity of positive control medicine, therefore formula（Ⅰ）It can be applied to prepare antitumor drug.

Claims (6)

1. a kind of sulfoamido derivative formula（Ⅰ）

Wherein, R is-(CH₂)_nCH₃, n=0 ~ 6.

2. a kind of sulfoamido derivative formula（Ⅰ）Synthetic route,

Wherein, R is-(CH₂)_nCH₃, n=0 ~ 6, it is characterized in that,

。

3. a kind of sulfoamido derivative formula（Ⅰ）Purposes in antitumor drug is prepared,

Wherein, R is-(CH₂)_nCH₃, n=0 ~ 6.

4. purposes as claimed in claim 3, it is characterized in that, the tumour is malignant tumour, and the malignant tumour is solid tumor Or non-physical knurl.

5. purposes as claimed in claim 4, it is characterized in that, the solid tumor is liver cancer, lung cancer, glioma, stomach cancer, ovum Nest cancer, breast cancer, the non-physical knurl are leukaemia.

6. a kind of anti-tumor compositions, which is characterized in that including sulfoamido derivative formula described in claim 1（Ⅰ）And doctor Acceptable auxiliary material on.