CN103755652A - Sulfonamide compound and application thereof - Google Patents
Sulfonamide compound and application thereof Download PDFInfo
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- CN103755652A CN103755652A CN201310719000.2A CN201310719000A CN103755652A CN 103755652 A CN103755652 A CN 103755652A CN 201310719000 A CN201310719000 A CN 201310719000A CN 103755652 A CN103755652 A CN 103755652A
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- 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
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- 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
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Abstract
The invention belongs to the technical field of medicines, and particularly relates to a sulfonamide compound and application thereof. The sulfonamide compound is as shown in formula (I) in the specification, an isomer of the compound as shown in formula (I) or a slat of the compound as shown in formula (I), wherein R is hydrogen, cyan, hydroxyl, halo-alkyl, alkoxy, alkoxy alkyl, alkylamino, alkylamino alkyl or R1; R1 is substituted carbonyl. Pharmacological activity screening results of the compound disclosed by the invention show that the compound has a good inhibiting effect on MCF-7 (human breast cancer cells) and HeLa (human cervical carcinoma cells), so the compound has good development and application prospects in anti-tumor aspect.
Description
Technical field
The invention belongs to medical technical field, 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 approximately 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, and its curative ratio is low, mortality ratio is high and have distributivity widely.In developed country, cancer has become the main reason that makes people lethal; In developing country, the mortality ratio of cancer occupies second in the mortality ratio of all diseases.Enquiry data demonstration, 2008, global cancer patients approximately 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 human life's No.1 killer.So far, countries in the world a large amount of human and material resources prevention, diagnosis and the treatments for tumour of having thrown people.The high lethality rate of tumour has and shifts and invasive ability mainly due to tumour cell, and the death of approximately 90% tumour patient comes from the transfer of tumour, yet early stage Results can improve result for the treatment of.If there is the small transfer in many places in focus before tumour is made a definite diagnosis, even if some malignant tumour still may be cured as guilt ball cancer.The antitumor drug of application is of a great variety clinically, and wherein chemotherapeutics mainly contains alkylating agent platinum complex antitumor drug, green onion lopps antitumor drug, destroys the microbiotic of DNA etc.The antitumor drug of finding high-efficiency low-toxicity is 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 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 replacing.
Described R
1for hydroxyl, halogen, alkyl, amino, haloalkyl, alkylthio alkyl, alkoxyalkyl or pyrimidyl replace or group as follows
be selected from the further imidazolidyl of replacement of following group, 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 be selected from the cyclic saturated hydrocarbon of 3～6 saturated carbon atoms formation or have the straight or branched saturated hydrocarbyl that 1～6 saturated carbon atom forms, 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 application for the preparation of anti-tumor compositions as active ingredient in general formula (I) compound, its salt or isomer.
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, and 2-(2-amino-5-(dimethylamino) phenyl)-N-(3-(trifluoromethyl) phenyl) Isonicotinamide of take makes as starting raw material route via I; Wherein, the preparation of intermediate 1 is referring to Bollu, and the record in the disclosed WO2010093845A1 document of Venkataiah obtains.
The present invention includes compound that above-mentioned general formula I comprises and be preparation composition that activeconstituents is mixed with and the preparation that forms of preparation.Formulation preparation method is: the compound dissolution that the present invention is contained makes formulation soln in 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 physiological saline to obtain the carbohydrate of 1-20%.Described organic solvent comprises polyoxyethylene glycol (PEG), ethanol, the combination solvent of propylene glycol or these solvents.
The compound of containing 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 synthetic compound of the present invention can be used for the activeconstituents of antitumor drug, can use separately, also can, antiviral drug combination antitumor with other.In the drug combination therapeutic process of indication of the present invention, comprise use at least one the compounds of this invention with and one or more anti-tumor virus drugs of reactive derivative and other together with use to increase general curative effect.Dose during drug combination and administration time should be determined according to rational therapy effect obtained in different situations.
The medicament compatibility of containing comprises the effective dose of the compound in general formula I." effective dose " herein refers to the consumption that can produce required this compound of result for the treatment of for institute's treatment target.This effective dose or dosage can be by having experience person according to the suggestion of different situations difference.Such as, the tumour kind for the treatment of is different, and the usage of medicine is different; Whether share etc. as other antitumor drugs or antiviral with other methods for the treatment of, dosage all can change.Can make any spendable preparation formulation.If some has alkalescence or acidic cpd and can form avirulent acid or salt, can use the form of the salt of this compound.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.; If any the alkaline compound as amine and suitable acid, can make the form of described salt; The compound of carboxylic-acid can form spendable salt with basic metal or alkaline-earth metal.
The compound of containing in formula of I of the present invention is general 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 with and 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.Compound dissolution is in water miscible organic solvent, non-protonic solvent, water-soluble lipid, cyclodextrin, lipid acid, phosphatide or in the mixed solvent of these solvents and make drug solution; Add again physiological saline to obtain the carbohydrate of 1-20%, as the aqueous solution of glucose.The preparation stabilization making therefrom for animal and clinical.
The compound in above-mentioned general formula I of take is the product medicine that active fraction preparation becomes, can be by oral or parenteral route administration, also can be by transplant medicine pump in body and additive method administration, the parenteral route administration of indication herein refers to subcutaneous intracutaneous, intramuscular, intravenously, intra-arterial, atrium in, in synovial membrane, in breastbone, in sheath, interior, the intracranial injection of wound site or drip infusion technique etc.By technician, use conventional method proportioning, mix and finally become needed pharmaceutical dosage form.Can be the outstanding solution of tablet, pill, capsule, electuary, syrup, injection liquid, freeze-dried powder formulation, emulsion, pulvis, lyophilized powder, dripping pill, emulsion suspension liquid, water, 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 the 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 present invention has advantages of: the compound that the present invention obtains, tumor cell line is had to good restraining effect, 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, pharmacology embodiment, 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 outside indicating, raw materials used all have commercially available.
Embodiment 1: compound (1) synthetic
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-(benzyl alkylsulfonyl)-2,6-difluorophenyl] methyl alcohol 10g (36.80mmol, 1.00equiv; 98%) with 70mL methylene dichloride, be dissolved in 100mL round-bottomed flask; add again triethylamine 11g (108.71mmol, 2.95equiv), then nitrogen protection; at 0 ℃, drip methylsulfonyl chloride 5.14g (44.87mmol; 1.22equiv), the about 10min of time for adding, and continue to stir 30min at 0 ℃; then naturally rise to room temperature and stirring 1h, reaction is finished.Add methylene dichloride 300mL dilute reaction solution; again with washing with purified water 100mL * 3; anhydrous sodium sulfate drying; concentrating under reduced pressure organic phase, finally adopts silica gel column chromatography separate mode to purify, and eluent is that petrol ether/ethyl acetate=2:1 obtains colorless oil [4-(benzyl alkylsulfonyl)-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) with 50mL DMF, be dissolved in 100mL round-bottomed flask, then add above-mentioned colorless oil 9.4g (27.29mmol, 1.20equiv), salt of wormwood 11.3g (81.76mmol, 2.99equiv), whole system stirs after 2h in 80 ℃ 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, finally adopts silica gel column chromatography separate mode to purify; eluent is that petrol ether/ethyl acetate=2:1 obtains white solid 3-([[4-(benzyl alkylsulfonyl)-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) with 8.0mL acetonitrile, be dissolved in 100mL round-bottomed flask, then add purified water 203mg (11.27mmol, 5.99equiv), acetic acid 561.6mg (9.35mmol, 4.97equiv), whole system is cooled to after 0 ℃ in ice-water bath, drips 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 ethyl acetate dilute reaction solution; with saturated aqueous common salt 100mL * 3 washing reaction liquid; 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=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.
Use 10mL pyridine amine solvent in 25mL round-bottomed flask 5-methyl-2-amino pyrimidine 336mg (3.08mmol, 3.84equiv), then add above-mentioned white solid (600mg, 0.80mmol, 1.00equiv), whole system stirs after 2h in 120 ℃ of oil baths, and reaction is finished.Vacuum concentration steams except pyridine, and the thick about 800mg of product adopts silica gel column chromatography separate mode to purify, and eluent is that petrol ether/ethyl acetate=1:1 obtains white solid compound (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: compound (2) synthetic
Adopt identical starting raw material with embodiment 1, but adopt thiazolamine in last one-tenth acid amides reaction process, then be synthetic route I according to the synthetic method of embodiment 1, can make 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: compound (3) synthetic
Adopt 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 be synthetic route I according to the synthetic method of embodiment 1, can make 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: compound (4) synthetic
Adopt identical starting raw material with embodiment, but adopt 1-phenylurea in last one-tenth acid amides reaction process, then be synthetic route I according to the synthetic method of embodiment 1, can make 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: compound (5) synthetic
Adopt identical starting raw material with embodiment 1, but in last one-tenth acid amides reaction process, adopt 1-(2-methoxy ethyl) urea, then be synthetic route I according to the synthetic method of embodiment 1, can make 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: compound (6) synthetic
Adopt identical starting raw material with embodiment 1, but in last one-tenth acid amides reaction process, adopt 2-(4-formyl piperazine-1) ethyl phosphonic acid, then be synthetic route I according to the synthetic method of embodiment 1, can make 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: compound (7) synthetic
Adopt identical starting raw material with embodiment 1, but in last one-tenth acid amides reaction process, adopt 2-(thiazolamine-4)-N-methyl-N-((2S, 3R, 4R, 5R)-2,3,4,5,6-penta hydroxyl oneself be) acid amides, according to the synthetic method of embodiment 1, be synthetic route I again, can make 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 tetramethyl-azo azoles salt colorimetry, i.e. mtt assay to MCF-7 (human breast cancer cell) and HeLa (human cervical carcinoma cell) tumour cell.Active in half-inhibition concentration (IC
50) represent, unit is μ M, positive control drug is 5 FU 5 fluorouracil (5-Fu).
Take MCF-7 cell as example:
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(are containing 3 * 10
4-5 * 10
4individual cell).Culture plate is put into CO
2incubator, at 37 ℃, 5%CO
2under condition, after culturing cell is adherent, add the testing compound of different concns, 4 concentration (1 * 10 of each compound test
-5, 1 * 10
-6, 1 * 10
-7, 1 * 10
-8mol/L), control group adds and the isopyknic solvent of administration group.Continuation is at CO
2in incubator in 37 ℃, 5%CO
2under condition, cultivate 72h.Every hole adds 20 μ L MTT solution (5mg/mL), in 37 ℃, continue to hatch 4h, end to cultivate, discard culture supernatant in hole, every hole adds 150 μ L DMSO, gentle agitation 10min, select 570nm wavelength, in microplate reader, measure each hole absorbance value (OD value), use the inhibiting rate of formula computerized compound to tumour cell below, and calculate 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, it is active that compound 4 and the 7 couples of MCF-7 and HeLa tumour cell have obvious inhibition, has the value of further research; Compound 1,2 and 3 pairs of tumour cells have all shown that weak inhibition is active, and Structure-activity Relationship shows H
2r in N-R for replace heterocycle shape carbonyl time be the anti-tumor activity that is conducive to improve compound, but likely reduce 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 improvement and conversion all should belong to the protection domain of claims of the present invention.
Claims (7)
1. a sulfamide compound, is characterized in that: 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 replacing.
2. by sulfamide compound claimed in claim 1, it is characterized in that: described R
1for hydroxyl, halogen, alkyl, amino, haloalkyl, alkylthio alkyl, alkoxyalkyl or pyrimidyl replace or group as follows
be selected from the further imidazolidyl of replacement of following group, 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.
3. by the sulfamide compound described in claim 1 or 2, it is characterized in that: 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:
4. an application for sulfamide compound claimed in claim 1, is characterized in that: described general formula (I) compound, its salt or isomer are for the preparation of anti-tumor drug.
5. by the application of sulfamide compound claimed in claim 4, it is characterized in that: using one or more application for the preparation of anti-tumor compositions as active ingredient in general formula (I) compound, its salt or isomer.
6. by the application of sulfamide compound claimed in claim 5, it is characterized in that: the weight percentage of the active ingredient in described anti-tumor compositions is 30-70%.
7. by the application of sulfamide compound claimed in claim 6, it is characterized in that: described anti-tumor compositions is tablet, capsule, powder, pill, granule or emulsion.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20050154039A1 (en) * | 2001-11-28 | 2005-07-14 | Marie-Odile Glacera Contour | 5-Sulphanyl-4h-1,2,4-triazole derivatives and their use as medicine |
| CN102395567A (en) * | 2009-02-12 | 2012-03-28 | 埃克塞利希斯股份有限公司 | Triazole and imidazole derivatives for use as tgr5 agonists in the treatment of diabetes and obesity |
| CN102781922A (en) * | 2009-12-11 | 2012-11-14 | 埃克塞利希斯股份有限公司 | TGR5 agonists |
-
2013
- 2013-12-20 CN CN201310719000.2A patent/CN103755652B/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20050154039A1 (en) * | 2001-11-28 | 2005-07-14 | Marie-Odile Glacera Contour | 5-Sulphanyl-4h-1,2,4-triazole derivatives and their use as medicine |
| CN102395567A (en) * | 2009-02-12 | 2012-03-28 | 埃克塞利希斯股份有限公司 | Triazole and imidazole derivatives for use as tgr5 agonists in the treatment of diabetes and obesity |
| CN102781922A (en) * | 2009-12-11 | 2012-11-14 | 埃克塞利希斯股份有限公司 | TGR5 agonists |
Non-Patent Citations (1)
| Title |
|---|
| 张文生，等: "含苯磺酰胺功能团的1，2，3-三唑类化合物的合成", 《化学试剂》, vol. 33, no. 4, 15 April 2011 (2011-04-15) * |
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| CN103755652B (en) | 2015-08-05 |
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