CN103755652B - A kind of sulfamide compound and application thereof - Google Patents

A kind of sulfamide compound and application thereof Download PDF

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CN103755652B
CN103755652B CN201310719000.2A CN201310719000A CN103755652B CN 103755652 B CN103755652 B CN 103755652B CN 201310719000 A CN201310719000 A CN 201310719000A CN 103755652 B CN103755652 B CN 103755652B
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compound
sulfamide
cancer
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salt
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CN103755652A (en
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卢久富
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Shaanxi University of Technology
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
    • C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
    • C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
    • C07D249/10—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D249/12—Oxygen or sulfur atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • 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
    • C07D417/02—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 two hetero rings
    • C07D417/12—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 two hetero rings linked by a chain containing hetero atoms as chain links

Abstract

The invention belongs to medical art, specifically a kind of sulfamide compound and application thereof.Sulfamide compound is as the salt of logical formula I, general formula (I) compound isomers or general formula (I) compound; Wherein, R is hydrogen, cyano group, hydroxyl, haloalkyl, alkoxyl group, alkoxyalkyl, alkylamino radical, alkylamino radical alkyl or R 1; Described R 1for the carbonyl replaced.The Pharmacological Activity Screening result of the compounds of this invention shows it has good restraining effect to MCF-7 (human breast cancer cell) and HeLa (human cervical carcinoma cell), has good anti-tumor aspect development prospect.

Description

A kind of sulfamide compound and application thereof
Technical field
The invention belongs to medical art, specifically a kind of sulfamide compound and application thereof.
Background technology
In recent years, tumour is a large chronic disease of puzzlement modern health, and its sickness rate is high, mortality ratio is high, recurrence rate is high, treatment is difficult.The annual whole world about has 7,000,000 people to die from cancer, accounts for 1/4th of total death toll.People talk " cancer " look and become, and generally believe that cancer is incurable disease, and this mainly comes from that its curative ratio is low, mortality ratio is high and has distributivity widely.In developed country, cancer has become the main reason making people lethal; In developing country, the mortality ratio of cancer occupies second in the mortality ratio of all diseases.Enquiry data shows, and 2008, global cancer patients about had 1,270 ten thousand people, and wherein death toll is up to 7,600,000.The World Health Organization (WHO) scholarly forecast, cancer will become the number one killer of human life.So far, prevention, the Diagnosis and Treat that a large amount of human and material resources of people are used for tumour is thrown in countries in the world.The high lethality rate of tumour has transfer and invasive ability mainly due to tumour cell, and the death of about 90% tumour patient comes from the transfer of tumour, but early stage Results then can improve result for the treatment of.If the small transfer in many places has occurred focus before tumour is made a definite diagnosis, even if some malignant tumour such as guilt ball cancer still may be cured.The antitumor drug applied clinically is of a great variety, and wherein chemotherapeutics mainly contains the microbiotic etc. of alkylating agent platinum complex antitumor medicine, green onion lopps antitumor drug, destruction DNA.Find the antitumor drug of high-efficiency low-toxicity and be still the important topic that scientist faces.
Summary of the invention
The object of the present invention is to provide a kind of sulfamide compound and application thereof.
For achieving the above object, the technical solution used in the present invention is:
A kind of sulfamide compound, sulfamide compound is as the salt of logical formula I, general formula (I) compound isomers or general formula (I) compound;
Wherein, R is hydrogen, cyano group, hydroxyl, haloalkyl, alkoxyl group, alkoxyalkyl, alkylamino radical, alkylamino radical alkyl or R 1; Described R 1for the carbonyl replaced.
Described R 1for hydroxyl, halogen, alkyl, amino, haloalkyl, alkylthio alkyl, alkoxyalkyl or pyrimidyl replace or group as follows be selected from the imidazolidyl that following group replaces further, 2-imidazolidyl, 3-imidazolidyl, pyrryl, 2H-pyrryl, 2-pyrrolinyl, pyrrolidyl, triazolyl, pyrazolyl, piperazinyl, pyridazinyl, pyrazinyl, triazinyl, morpholinyl or thio-morpholinyl; Y is S, O, NH or N-alkyl.
Wherein, haloalkyl is selected from the cyclic saturated hydrocarbon that 3 ~ 6 saturated carbon atoms are formed or the straight or branched saturated hydrocarbyl with 1 ~ 6 saturated carbon atom formation, and the halogen in haloalkyl is fluorine, chlorine, the substituting group of bromine or iodine.
Described sulfamide compound is compound (1), compound (2), compound (3), compound (4), compound (5), compound (6) or compound (7), and concrete structure formula is as follows:
An application for sulfamide compound, described general formula (I) compound, its salt or isomer are for the preparation of anti-tumor drug.
Using one or more in general formula (I) compound, its salt or isomer as the application of active ingredient for the preparation of anti-tumor compositions.
The weight percentage of the active ingredient in described anti-tumor compositions is 30-70%.
Described anti-tumor compositions is tablet, capsule, powder, pill, granule or emulsion.
The preparation of sulfamide compound, concrete synthetic route is as follows, is namely that starting raw material route via I obtains with 2-(2-amino-5-(dimethylamino) phenyl)-N-(3-(trifluoromethyl) phenyl) Isonicotinamide; Wherein, the preparation of intermediate 1 obtains see the record in WO2010093845A1 document disclosed in Bollu, Venkataiah.
The present invention includes the preparation that compound that above-mentioned general formula I comprises is the formulation ingredients that is mixed with of activeconstituents and its preparation composition.Formulation preparation method for: obtain formulation soln in compound dissolution the present invention contained to the tensio-active agent of water miscible organic solvent, nonionic, water miscible lipoid, various cyclodextrin, lipid acid, fatty acid ester, phosphatide or its combination solvent; Add the carbohydrate that physiological saline obtains 1-20%.Described organic solvent comprises polyoxyethylene glycol (PEG), ethanol, the combination solvent of propylene glycol or these solvents.
The compound contained in general formula I of the present invention and prodrug are for the preparation for the treatment of, prevention or alleviate antitumor drug or pharmaceutical preparation, and active constituents of medicine is the compound shown in one or more general formula Is.Be particularly useful for the cancer that treatment or alleviation tissue or organ tumor cell cause.The preferred colorectal carcinoma of indication cancer, liver cancer, lymphoma, lung cancer, the esophageal carcinoma, mammary cancer, central nerve neuroma, melanoma, ovarian cancer, cervical cancer, kidney, leukemia, prostate cancer, carcinoma of the pancreas, bladder cancer, the rectum cancer or cancer of the stomach etc.
The compound of the present invention's synthesis can be used for the activeconstituents of antitumor drug, can be used alone, also can, antiviral drug combination antitumor with other.In the drug combination therapeutic process of indication of the present invention, comprise using together with at least one the compounds of this invention and one or more anti-tumor virus drugs of its reactive derivative and other and use to increase general curative effect.Dose during drug combination and administration time should be determined according to most rational therapy effect acquired when different.
The medicament compatibility contained comprises the effective dose of the compound in general formula I." effective dose " herein refers to the consumption that can produce this compound required for result for the treatment of for institute's treatment target.This effective dose or dosage can by there being experience person different according to the suggestion of different situations.Such as, the tumor class for the treatment of is different, and the usage of medicine is different; Whether share with other methods for the treatment of such as other antitumor drugs or antiviral, dosage all can change.Any spendable preparation formulation can be made.If some has alkalescence or acidic cpd also can form avirulent acid or salt, the form of the salt of this compound can be used.In pharmacy, spendable organic acid salt comprises spendable anion salt on physiology, as toluenesulfonate, metilsulfate, acetate, benzoate, Citrate trianion, malate, tartrate, maleate, succinate, ascorbate salt or glycerophosphate etc.; Spendable inorganic salt comprise muriate, bromide, fluorochemical, iodide, vitriol, nitrate, supercarbonate, carbonate or phosphoric acid salt etc.; The form of described salt can be made if any the compound of the alkalescence as amine and suitable acid; The compound of carboxylic-acid can form spendable salt with basic metal or alkaline-earth metal.
The compound contained in formula of I of the present invention is generally readily soluble in the mixed solvent of organic solvent, water-soluble solvent and organic solvent and water-soluble solvent and water.Water-soluble solvent preferred alcohols, poly ethylene glycol, N-methyl-2-pyrrolinone, N,N-dimethylacetamide, DMF, methyl-sulphoxide, acetonitrile and its share.Described alcohol particular methanol, ethanol, Virahol, glycerol or ethylene glycol.The compounds of this invention can mix with conventional preparations carrier and make preparation.Drug solution is obtained in compound dissolution to water miscible organic solvent, non-protonic solvent, water-soluble lipid, cyclodextrin, lipid acid, phosphatide or in the mixed solvent of these solvents; Add the carbohydrate that physiological saline obtains 1-20% again, as the aqueous solution of glucose.Preparation stabilization obtained therefrom for animal and clinical.
With the product medicine that compound in above-mentioned general formula I becomes for active fraction preparation, oral or parenteral administration can be passed through, also by transplant medicine pump in body and additive method administration, herein the parenteral administration of indication refer in subcutaneous intracutaneous, intramuscular, intravenously, intra-arterial, atrium, in synovial membrane, in breastbone, in sheath, in wound site, intracranial injection or drip infusion technique etc.Use conventional method proportioning by technician, mixing finally becomes required pharmaceutical dosage form.Can be tablet, pill, capsule, electuary, syrup, injection liquid, freeze-dried powder formulation, emulsion, pulvis, lyophilized powder, dripping pill, emulsion suspension liquid, water hang solution, the aqueous solution, colloid, colloidal solution, sustained release preparation, nanometer formulation or with other forms of formulation for animal or clinical.
Compound in general formula I of the present invention is used for the treatment of or alleviates the preparation of cancer drug of a certain tissue or organ.Indication cancer comprises but is not only limited to colorectal carcinoma, liver cancer, lymphoma, lung cancer, the esophageal carcinoma, mammary cancer, central nerve neuroma, melanoma, ovarian cancer, cervical cancer, kidney, leukemia, prostate cancer, carcinoma of the pancreas, bladder cancer, the rectum cancer or cancer of the stomach etc.
The advantage that the present invention has: the compound that the present invention obtains, has good restraining effect to tumor cell line, and it can be prepared into tablet, capsule, powder, pill, granule or emulsion simultaneously.
Accompanying drawing explanation
Fig. 1 provides compound (1) H NMR collection of illustrative plates for the embodiment of the present invention;
Fig. 2 provides compound (2) H NMR collection of illustrative plates for the embodiment of the present invention;
Fig. 3 provides compound (3) H NMR collection of illustrative plates for the embodiment of the present invention;
Fig. 4 provides compound (4) H NMR collection of illustrative plates for the embodiment of the present invention;
Fig. 5 provides compound (5) H NMR collection of illustrative plates for the embodiment of the present invention;
Fig. 6 provides compound (6) H NMR collection of illustrative plates for the embodiment of the present invention;
Fig. 7 provides compound (7) H NMR collection of illustrative plates for the embodiment of the present invention.
Embodiment
Following synthetic example, Pharmacological Examples, comparative example result can be used to further illustrate the present invention, but do not mean that restriction the present invention, in the present invention except as otherwise indicate outside, raw materials used all have commercially available.
Embodiment 1: the synthesis of compound (1)
Adopt the mode of synthetic route I, wherein above-mentioned H 2n-R is 5-methyl-2-amino pyrimidine, and detailed step is as follows.
By [4-(benzylsulphonyl)-2; 6-difluorophenyl] methyl alcohol 10g (36.80mmol; 1.00equiv; 98%) be dissolved in 100mL round-bottomed flask with 70mL methylene dichloride; add triethylamine 11g (108.71mmol again; 2.95equiv); then nitrogen protection; methylsulfonyl chloride 5.14g (44.87mmol is dripped at 0 DEG C; 1.22equiv), time for adding is about 10min, and continues to stir 30min at 0 DEG C; then naturally rise to room temperature at stirring 1h, reaction is finished.Add methylene dichloride 300mL dilute reaction solution; wash with purified water 100mL × 3 again; anhydrous sodium sulfate drying; concentrating under reduced pressure organic phase, finally adopt silica gel column chromatography separate mode to purify, eluent is that petrol ether/ethyl acetate=2:1 obtains colorless oil [4-(benzylsulphonyl)-2; 6-difluorophenyl] methanesulfonates 12.0g; productive rate 88.0%, (ES, m/z): 345.2 [M+H] + 1, 347.2 [M+H+2] + 1.
By 5-[2-(3,4-Dimethoxyphenyl) propyl group-2]-4-(4-fluorophenyl)-4H-1,2,4-triazole-3-mercapto alcohol 10.2g (27.31mmol, 1.00equiv) use 50mL N, dinethylformamide is dissolved in 100mL round-bottomed flask, add above-mentioned colorless oil 9.4g (27.29mmol again, 1.20equiv), salt of wormwood 11.3g (81.76mmol, 2.99equiv), after whole system stirs 2h in 80 DEG C of oil baths, add the quencher of 300mL purified water, reaction is finished.With saturated aqueous common salt 100mL × 3 washing reaction liquid; anhydrous sodium sulfate drying; concentrating under reduced pressure organic phase; silica gel column chromatography separate mode is finally adopted to purify; eluent is that petrol ether/ethyl acetate=2:1 obtains white solid 3-([[4-(benzylsulphonyl)-2; 6-difluorophenyl] methyl] alkylsulfonyl)-5-[2-(3; 4-Dimethoxyphenyl) propyl group-2]-4-(4-fluorophenyl)-4H-1; 2; 4-triazole 15.0g; productive rate 88.0%, (ES, m/z): 622.2 [M+H] + 1, 624.2 [M+H+2] + 1.
By above-mentioned white solid 1.17g (1.88mmol, 1.00equiv) be dissolved in 100mL round-bottomed flask with 8.0mL acetonitrile, then add purified water 203mg (11.27mmol, 5.99equiv), acetic acid 561.6mg (9.35mmol, 4.97equiv), after whole system is cooled to 0 DEG C in ice-water bath, drip 1-chlorine tetramethyleneimine-2,5-diketone 744mg (5.57mmol, 2.96equiv), then naturally rise to room temperature and continue to stir 2h, reaction is finished.Add 200mL diluted ethyl acetate reaction solution; with saturated aqueous common salt 100mL × 3 washing reaction liquid; anhydrous sodium sulfate drying; concentrating under reduced pressure organic phase; silica gel column chromatography separate mode is finally adopted to purify; eluent is that petrol ether/ethyl acetate=1:1 obtains white solid [([5-[2-(3; 4-Dimethoxyphenyl) propyl group-2]-4-(4-fluorophenyl)-4H-1; 2; 4-triazole-3] alkylsulfonyl) methyl]-3,5-difluorophenyl-1-SULPHURYL CHLORIDE 1.4g, productive rate 88.0%; (ES, m/z): 598.2 [M+H] + 1, 600.2 [M+H+2] + 1.
Used by 5-methyl-2-amino pyrimidine 336mg (3.08mmol, 3.84equiv) 10mL pyridine amine solvent in 25mL round-bottomed flask, then add above-mentioned white solid (600mg, 0.80mmol, 1.00equiv), after whole system stirs 2h in 120 DEG C of oil baths, reaction is finished.Vacuum concentration steams except pyridine, and thick product is about 800mg, adopts silica gel column chromatography separate mode to purify, eluent is that petrol ether/ethyl acetate=1:1 obtains compound as white solid (1) 96.0mg, productive rate 17.0%, (ES, m/z): 671.2 [M+H] + 1, 673.2 [M+H+2] + 1.H NMR(300MHz,CD 3OD)δ:8.14(s,2H),7.48(d,J=7.2Hz,2H),6.85(s,3H),6.50～6.33(m,4H),4.13(s,2H),3.87(s,3H),3.72(s,3H),2.11(s,3H),1.62(s,6H)。See Fig. 1.
Embodiment 2: the synthesis of compound (2)
Adopts identical starting raw material with embodiment 1, but adopt thiazolamine in last one-tenth acid amides reaction process, then according to the synthetic method of embodiment 1 and synthetic route I, can obtain compound (2), concrete structure formula is as follows:
(ES,m/z):662.2[M+H] +1，664.2[M+H+2] +1;H NMR(300MHz,CDCl 3)δ:7.42(d,J=7.5Hz,2H),6.91～6.87(m,5H),6.47(s,2H),6.34～6.30(m,3H),4.16(s,2H),3.85(s,3H),1.74(s,3H),1.64(s,6H)。See Fig. 2.
Embodiment 3: the synthesis of compound (3)
Adopts identical starting raw material with embodiment 1, but in last one-tenth acid amides reaction process, adopt 3,4-dimethyl-5-ammonia base oxazole, then according to the synthetic method of embodiment 1 and synthetic route I, can obtain compound (3), concrete structure formula is as follows:
(ES,m/z):674.2[M+H] +1，676.2[M+H+2] +1;H NMR(300MHz,CDCl 3)δ:7.41(d,J=7.5Hz,2H),6.90～6.83(m,3H),6.48(s,2H),6.35～6.30(m,3H),4.16(s,2H),3.86(s,3H),3.69(s,3H),2.06(s,3H),1.75(s,3H),1.63(s,6H)。See Fig. 3.
Embodiment 4: the synthesis of compound (4)
Adopts identical starting raw material with embodiment, but adopt 1-phenylurea in last one-tenth acid amides reaction process, then according to the synthetic method of embodiment 1 and synthetic route I, can obtain compound (4), concrete structure formula is as follows:
(ES, m/z): 698.2 [M+H] + 1, 700.2 [M+H+2] + 1; H NMR (300MHz, CDCl 3) δ: 7.62 (d, J=6.6Hz, 2H), 7.41 ~ 7.39 (m, 2H), 7.32 ~ 7.27 (m, 2H), 7.11 ~ 7.07 (m, 1H), 6.91 ~ 6.80 (m, 3H), 6.46 ~ 6.41 (m, 2H), 6.33 ~ 6.28 (m, 2H), 4.18 (s, 2H), 3.85 (s, 3H), 3.68 (s, 3H), 1.60 (s, 6H), are shown in Fig. 4.
Embodiment 5: the synthesis of compound (5)
Adopts identical starting raw material with embodiment 1, but adopt 1-(2-methoxy ethyl) urea in last one-tenth acid amides reaction process, then according to the synthetic method of embodiment 1 and synthetic route I, can obtain compound (5), concrete structure formula is as follows:
(ES,m/z):680.2[M+H] +1，682.2[M+H+2] +1;H NMR(300MHz,CDCl 3)δ:7.55(d,J=6.6Hz,2H),6.96～6.84(m,3H),6.51～6.49(m,2H),6.43～6.38(m,2H),4.19(s,2H),3.86(s,3H),3.72(s,3H),3.42(t,J=5.4Hz,2H),3.30(t,J=5.4Hz,2H),1.64(s,6H)。See Fig. 5.
Embodiment 6: the synthesis of compound (6)
Identical starting raw material is adopted with embodiment 1; but in last one-tenth acid amides reaction process, adopt 2-(4-formyl piperazine-1) ethyl phosphonic acid; again according to synthetic method and the synthetic route I of embodiment 1, can obtain compound (6), concrete structure formula is as follows:
(ES,m/z):799.2[M+H] +1，801.2[M+H+2] +1;H NMR(300MHz,CDCl 3)δ:7.44(d,J=6.4Hz,2H),6.84～6.74(m,3H),6.40～6.31(m,4H),4.03(s,2H),3.75(s,3H),3.62～3.60(m,6H),3.46～3.27(m,3H),2.03～1.94(m,2H),1.52(s,6H)。See Fig. 6.
Embodiment 7: the synthesis of compound (7)
Identical starting raw material is adopted with embodiment 1, but in last one-tenth acid amides reaction process, adopt 2-(thiazolamine-4)-N-methyl-N-((2S, 3R, 4R, 5R)-2,3,4,5, namely 6-penta hydroxyl own) acid amides, again according to synthetic method and the synthetic route I of embodiment 1, can obtain compound (7), concrete structure formula is as follows:
(ES,m/z):897.2[M+H] +1，899.2[M+H+2] +1;H NMR(300MHz,CDCl 3)δ:7.31(s,2H),6.83～6.77(m,3H),6.44～6.35(m,4H),4.13(s,2H),3.94～3.81(m,2H),3.77(s,3H),3.73～3.64(m,3H),3.61～3.55(m,6H),3.53～3.30(m,3H),3.08(s,1H)2.60(s,2H),1.54(s,6H)。See Fig. 7.
Embodiment 8: compound pharmacological evaluation
Testing compound as research object, adopts tetrazolium-based colorimetric assay, i.e. mtt assay to MCF-7 (human breast cancer cell) and HeLa (human cervical carcinoma cell) tumour cell.Active half-inhibition concentration (IC 50) represent, unit is μM, and positive control drug is 5 FU 5 fluorouracil (5-Fu).
For MCF-7 cell:
Get the MCF-7 cell of 0.25% tryptic digestion monolayer culture, with the RPMI1640 nutrient solution containing 10% foetal calf serum.Be made into single cell suspension, be inoculated in 96 orifice plates, every hole 200 μ L(is containing 3 × 10 4-5 × 10 4individual cell).Culture plate is put into CO 2incubator, at 37 DEG C, 5%CO 2under condition, add the testing compound of different concns after culturing cell is adherent, each compound tests 4 concentration (1 × 10 -5, 1 × 10 -6, 1 × 10 -7, 1 × 10 -8mol/L), control group adds solvent isopyknic with administration group.Continue at CO 2in 37 DEG C, 5%CO in incubator 272h is cultivated under condition.Every hole adds 20 μ L MTT solution (5mg/mL), continue to hatch 4h in 37 DEG C, stop to cultivate, discard culture supernatant in hole, every hole adds 150 μ L DMSO, gentle agitation 10min, select 570nm wavelength, microplate reader measures each hole absorbance value (OD value), with the inhibiting rate of formulae discovery compound on tumor cell the following, and calculates IC 50.Repeated test 3 times, averages as net result.
Compound MCF-7(IC 50μM) HeLa(IC 50μM)
5-Fu 5.58 4.77
(1) 17.41 13.58
(2) 20.42 18.94
(3) 15.40 14.22
(4) 7.28 6.74
(5) ＞100 18.91
(6) 12.24 13.18
(7) 7.65 7.29
Known by above-mentioned data, compound 4 and 7 pairs of MCF-7 and HeLa tumour cells have obvious inhibit activities, have the value of research further; Compound 1,2 and 3 pair of tumour cell all shows more weak inhibit activities, and Structure-activity Relationship shows H 2r in N-R is the anti-tumor activity being conducive to improving compound when being the heterocycle shape carbonyl replaced, but likely reduces its anti-tumor activity when it for chain or chain carbonyl.
Should be understood that, for those of ordinary skills, can be improved according to the above description or convert, and all these improve and convert the protection domain that all should belong to claims of the present invention.

Claims (5)

1. a sulfamide compound, it is characterized in that: sulfamide compound is compound (1), compound (2), compound (3), compound (4), compound (5), compound (6) or compound (7), and concrete structure formula is as follows:
2. an application for sulfamide compound according to claim 1, is characterized in that: described sulfamide compound or its salt are for the preparation of anti-tumor drug.
3. by the application of sulfamide compound according to claim 2, it is characterized in that: using described sulfamide compound or its salt as the application of active ingredient for the preparation of anti-tumor compositions.
4., by the application of sulfamide compound according to claim 3, it is characterized in that: the weight percentage of the active ingredient in described anti-tumor compositions is 30-70%.
5., by the application of sulfamide compound according to claim 4, it is characterized in that: described anti-tumor compositions is tablet, capsule, powder, pill, granule or emulsion.
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