CN104693182A - Amide compounds having antineoplastic activity and application thereof - Google Patents

Amide compounds having antineoplastic activity and application thereof Download PDF

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Publication number
CN104693182A
CN104693182A CN201510117809.7A CN201510117809A CN104693182A CN 104693182 A CN104693182 A CN 104693182A CN 201510117809 A CN201510117809 A CN 201510117809A CN 104693182 A CN104693182 A CN 104693182A
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compound
amides
general formula
application
tumor
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卢久富
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Shaanxi University of Technology
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Shaanxi University of Technology
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
    • C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
    • C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
    • C07D241/14—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members 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
    • C07D241/20—Nitrogen atoms

Abstract

The invention relates to the technical field of drugs, and specifically relates to amide compounds having an antineoplastic activity, as well as an application thereof. The amide compounds are as a general formula (I), a compound isomer of the general formula (I) or a salt of the compound of the general formula (I), wherein R1, R2, R3, R4 and R5 can be the same or different, and R1, R2, R3, R4 and R5 can be selected from hydrogen, halogen, cyanogroup, hydroxyl, halogenated alkyl, alkoxy, alkoxy alkyl, alkyl amino or alkyl amino alkyl; X is oxygen atoms, sulphur atoms, carbon atoms, or nitrogen atoms. It is shown by pharmacological activity screening results that the amide compounds having the antineoplastic activity have good inhibiting effects to MCF-7 (human breast cancer cells), HeLa (human cervical cancer cells) and BeL7402 (human hepatoma carcinoma cells). The amide compounds having the antineoplastic activity are of excellent development and application prospects in the anti-tumor field.

Description

A kind of amides and application thereof with anti-tumor activity
Technical field
The invention belongs to medical art, specifically a kind of amides and application thereof with anti-tumor activity.
Background technology
Malignant tumour as one of larger public health problem in the whole world, the greatly health of harm humans, and will first killer of the new millennium mankind be become.From world wide, global new cancer cases 1,010 ten thousand, dead 6,200,000 in 2000, pathogenesis of cancer numbers in 2008 and death toll rise to 1,266 ten thousand and 7,560,000 respectively, and estimating 2015 will have 15,000,000 new cases.Meanwhile, malignant tumour is no longer the serious disease of advanced industrial country, and developing country is faced with larger Disease Spectrum.Within 2008, Incidence number developing country accounts for 56%; The cancer patients of 2009 80% concentrates on middle and low income country rank, and by 2015, developing country estimated at 9,000,000 people and dies from cancer.The various characteristics such as new drug demonstrates wider antitumor spectra in recent years, efficiently, easily tolerates, easy to use.In the future, searching has no side effect and new antitumoral medicine may become a main development direction efficiently, antimetabolite, topoisomerase enzyme inhibitor and Antitubulin will further develop, molecular targeted agents is if angiogenesis inhibitor, protein tyrosine kinase inhibitor etc. are by fast development, gene therapy medicament will complications develop, but new type antineoplastic medicine research and development will reach real tumour of curing also needs a very long process.
Summary of the invention
The object of the present invention is to provide a kind of amides and the application thereof with anti-tumor activity.
For achieving the above object, the technical solution used in the present invention is:
Have an amides for anti-tumor activity, amides is as the salt of logical formula I, general formula (I) compound isomers or general formula (I) compound;
Wherein: R 1, R 2, R 3, R 4, R 5what may be the same or different is selected from hydrogen, halogen, cyano group, hydroxyl, haloalkyl, alkoxyl group, alkoxyalkyl, alkylamino radical or alkylamino radical alkyl; X is oxygen, sulphur, carbon or nitrogen-atoms;
Wherein haloalkyl is selected from the cyclic saturated hydrocarbon that 3 ~ 6 saturated carbon atoms are formed, the straight or branched saturated hydrocarbyl with 1 ~ 6 saturated carbon atom formation; Halogen in haloalkyl is fluorine, chlorine, the substituting group of bromine or iodine.
Described amides is compound (1), compound (2), compound (3), compound (4), compound (5) or compound (6), and concrete structure formula is as follows:
Have an application for the amides of anti-tumor activity, 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 30-80%.
Described anti-tumor compositions is tablet, capsule, powder, pill, granule or emulsion.
The advantage that the present invention has: the compound that the present invention obtains, has good restraining effect to tumor cell line, and compound and one or more pharmaceutical carriers or vehicle are prepared into tablet, capsule, powder, pill, granule or emulsion.
Accompanying drawing explanation
The collection of illustrative plates of the compound (1) that Fig. 1 provides for the embodiment of the present invention.
The collection of illustrative plates of the compound (2) that Fig. 2 provides for the embodiment of the present invention.
The collection of illustrative plates of the compound (3) that Fig. 3 provides 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.
The amides with anti-tumor activity obtains according to the preparation of following synthetic route, specifically with 5-bromo-pyrazine-2-amine for starting raw material, at Pd (PPh 3) 4with under sodium carbonate alkaline condition, alkylated reaction is carried out with the dihydroxyl boron compound replaced, 2-nitrobenzoyl chloride chloro-with 5-carries out into acid amides and reacts again, amination reaction is carried out in the basic conditions again with the amino-complex replaced, react that to reduce nitro be corresponding amino again with palladium/carbon, amino finally after reduction and the carboxylic compound of replacement carry out being condensed into acid amides and react, target compound.
Synthetic route 1:
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.
Embodiment 1: the synthesis of compound (1)
By 5-bromo-pyrazine-2-amine 4.0mg (22.99mmol, 1.00equiv) be dissolved in 1, in the mixed solution that 4-dioxane 60mL and anhydrous methanol 23mL forms, add 3-(trifluoromethyl) phenylo boric acid 4.46g (23.48mmol more respectively, 1.02equiv), Pd (PPh 3) 4532mg (0.46mmol, 0.02equiv), salt of wormwood 4.88g (46.04mmol, 2.00equiv) and purified water 23mL.Under nitrogen protection condition; 135 DEG C of stirrings are spent the night; reaction is finished; concentrating under reduced pressure steams except first alcohol and water, and finally adopt silica gel column chromatography separating-purifying, eluent is petrol ether/ethyl acetate=5:1 (v/v); obtain light yellow solid 5-(3-(trifluoromethyl) phenyl) pyrazine-2-amine 4.4g; yield 80%, (ES, m/z): 240.2 [M+H] + 1, 242.2 [M+H+2] + 1.
By above-mentioned light yellow oil 1.3g (5.43mmol, 1.00equiv) be dissolved in the mixing solutions of methylene dichloride 15mL and pyridine 2mL composition, 5-chloro-2-nitrobenzoyl chloride 1.2g (5.45mmol is dripped at-10 DEG C, 1.00equiv) be dissolved in the diluent in 5mL methylene dichloride, dropping terminates the rear room temperature that naturally rises to and stirs 2h again, reaction is finished, add 100mL dchloromethane reaction system, dilute hydrochloric acid 100mL × 2 of 10% are used to wash again, anhydrous sodium sulfate drying, concentrating under reduced pressure, obtain the chloro-2-nitro of light yellow solid 5--N-(5-(3-(trifluoromethyl) phenyl) pyrazine-2) benzamide crude product 2.0g, directly cast single step reaction.
By above-mentioned yellow oil 2.0g (4.73mmol, 1.00equiv) be dissolved in 30mL N, in dinethylformamide, add piperidinyl-1 .0g (11.74mmol again, 2.50equiv) with salt of wormwood 2.0g (11.74mmol, 2.50equiv), whole system is heated to 100 DEG C of stirrings and spends the night, reaction is finished, add 150mL diluted ethyl acetate reaction system, purified water 50mL × 2 are used to wash and saturated aqueous common salt 50mL × 2 more respectively, anhydrous sodium sulfate drying, concentrating under reduced pressure, finally volume ratio is adopted to be normal hexane: this oily matter of ethyl acetate=1:1 (v/v) crystallization, obtain off-white color solid 2-nitro-5-(piperidines-1)-N-(5-(3-(trifluoromethyl) phenyl) pyrazine-2) benzamide 1.7g, yield 76.0%, (ES, m/z): 472.2 [M+H] + 1, 474.2 [M+H+2] + 1.
By above-mentioned off-white color solid 560mg (1.20mmol, 1.00equiv) be placed in the round-bottomed flask of 50mL, add methylene dichloride 20mL and tetrahydrofuran (THF) 8mL, add solid palladium/carbon 560mg again, hydrogen is imported under reaction liquid level, stirring at room temperature 1h, reaction is finished, filter, concentrating under reduced pressure, finally adopt silica gel column chromatography separating-purifying, eluent is petrol ether/ethyl acetate=1:1, obtain white solid 2-amino-5-(piperidines-1)-N-(5-(3-(trifluoromethyl) phenyl) pyrazine-2) benzamide 400mg, yield 76.0%, (ES, m/z): 442.2 [M+H] + 1, 444.2 [M+H+2] + 1.
By picolinic acid 74mg (0.60mmol, 1.10equiv) be dissolved in 5mL N, in dinethylformamide, add HATU 816mg (2.18mmol, 4.00equiv) with N-ethyl-N-iospropyl propyl group-2-amine 140mg (2.16mmol, 4.00equiv), 240mg (0.54mmol is dripped again toward above-mentioned system, 1.00equiv) 2-amino-5-(piperidines-1)-N-(5-(3-(trifluoromethyl) phenyl) pyrazine-2) benzamide is dissolved in 5mL N, the diluent of dinethylformamide, stirred overnight at room temperature, reaction is finished, add 100mL diluted ethyl acetate reaction system, use the washing of aqueous ammonium chloride solution 100mL × 3 and the washing of saturated aqueous common salt 100mL × 3 of 10% again, finally wash organic phase by purified water again, anhydrous sodium sulfate drying, concentrating under reduced pressure, adopt silica gel column chromatography separating-purifying, eluent is that petrol ether/ethyl acetate=1:1 obtains compound as white solid (1) 76.0mg, yield 52.0%, (ES, m/z): 547.2 [M+H] + 1, 549.2 [M+H+2] + 1.H NMR(300MHz,CD 3OD)δ:12.16(s,1H),11.61(s,1H),9.49(s,1H),9.27(s,1H),8.74(d,J＝3.9Hz,1H),8.56(d,J＝8.7Hz,1H),8.49(s,2H),8.15(m,1H),8.06(m,1H),7.06(m,4H),7.47(s,1H),3.37(d,4H),1.75(s,4H),1.60(s,2H)。See Fig. 1.
Embodiment 2: the synthesis of compound (2)
Difference from Example 1 is, the carboxylic compound that final step and the aminocompound of replacement carry out into acid amides is 4-(((2-(diethylamino) ethyl) (methyl) is amino) methyl) phenylformic acid, according to synthetic method and the synthetic route I of embodiment 1, can obtain compound (2), concrete structure formula is as follows:
(ES, m/z): 688.2 [M+H] + 1, 690.2 [M+H+2] + 1; H NMR (300MHz, CDCl 3) δ: 11.49 (s, 1H), 11.05 (s, 1H), 9.43 (s, J=1.2Hz, 1H), 9.24 (s, J=1.2Hz, 1H), 8.46 (s, 2H), 8.08 (d, J=8.7Hz, 1H), 7.94 (d, J=7.8Hz, 2H), 7.81 (m, 2H), 7.60 (s, 2H), 7.49 (s, 1H), 7.24 (d, J=8.4Hz, 1H), 3.15 (m, 12H), 1.67 (s, 4H), 1.58 (s, 2H), 1.16 (d, J=7.2Hz, 6H), see Fig. 2.
Embodiment 3: the synthesis of compound (3)
The carboxylic compound carrying out into acid amides with embodiment 1 final step and the aminocompound of replacement is 3-(((2-(diethylamino) ethyl) (methyl) is amino) methyl) phenylformic acid, again according to synthetic method and the synthetic route I of embodiment 1, can obtain compound (3), concrete structure formula is as follows:
(ES, m/z): 688.2 [M+H] + 1, 690.2 [M+H+2] + 1; H NMR (300MHz, CDCl 3) δ: 11.51 (s, 1H), 11.02 (s, 1H), 9.44 (d, J=1.2Hz, 1H), 9.24 (d, J=1.2Hz, 1H), 8.46 (s, 1H), 8.03 (m, 3H), 7.84 (m, 2H), 7.63 (d, J=8.4Hz, 2H), 7.49 (s, 1H), 7.26 (d, J=7.2Hz, 1H), 3.15 (m, 12H), 1.68 (m, 6H), 1.17 (m, 6H), are shown in Fig. 3.
Embodiment 4: the synthesis of compound (4)
Difference from Example 1 is, the aminocompound that the 3rd step carries out the replacement of alkylated reaction is dimethylamine hydrochloride, and according to synthetic method and the synthetic route I of embodiment 1, can obtain compound (4), concrete structure formula is as follows:
(ES,m/z):507.2[M+H] +1，509.2[M+H+2] +1；H NMR(300MHz,CDCl 3)δ:12.17(s,1H),11.63(s,1H),9.50(s,1H),9.29(s,1H),8.75(d,J＝3.9Hz,1H),8.57(d,J＝8.7Hz,1H),8.49(s,2H),8.19(m,1H),8.08(m,1H),7.07(m,4H),7.48(s,1H),2.76(s,6H)。
Embodiment 5: the synthesis of compound (5)
Difference from Example 1 is, the carboxylic compound that final step and the aminocompound of replacement carry out into acid amides is 4-(((2-(diethylamino) ethyl) (methyl) is amino) methyl) phenylformic acid, according to synthetic method and the synthetic route I of embodiment 1, can obtain compound (5), concrete structure formula is as follows:
(ES,m/z):648.2[M+H] +1，650.2[M+H+2] +1；H NMR(300MHz,CDCl 3)δ:11.50(s,1H),11.06(s,1H),9.44(s,J＝1.2Hz,1H),9.27(s,J＝1.2Hz,1H),8.48(s,2H),8.10(d,J＝8.7Hz,1H),7.96(d,J＝7.8Hz,2H),7.82(m,2H),7.64(s,2H),7.50(s,1H),7.25(d,J＝8.4Hz,1H),3.13(m,10H),1.69(s,4H),2.78(s,6H)。
Embodiment 6: the synthesis of compound (6)
The carboxylic compound carrying out into acid amides with embodiment 1 final step and the aminocompound of replacement is 3-(((2-(diethylamino) ethyl) (methyl) is amino) methyl) phenylformic 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):648.2[M+H] +1，650.2[M+H+2] +1；H NMR(300MHz,CDCl 3)δ:11.52(s,1H),11.03(s,1H),9.46(d,J＝1.2Hz,1H),9.25(d,J＝1.2Hz,1H),8.47(s,1H),8.05(m,3H),7.86(m,2H),7.65(d,J＝8.4Hz,2H),7.49(s,1H),7.27(d,J＝7.2Hz,1H),3.16(m,14H),2.77(m,6H),。
Embodiment 7: compound pharmacological evaluation
Testing compound is to MCF-7 (human breast cancer cell), and HeLa (human cervical carcinoma cell) tumour cell and BeL7402 (human liver cancer cell), as research object, adopt tetrazolium-based colorimetric assay, i.e. mtt assay.Active half-inhibition concentration (IC 50) represent, unit be μM, is to contrast medicine with 5 FU 5 fluorouracil.For MCF-7 cell:
Get the MCF-7 cell of 0.25% tryptic digestion monolayer culture, with the RPMI1640 containing 10% foetal calf serum, nutrient solution is made into single cell suspension, is inoculated in 96 orifice plates, and 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 (2) is best to MCF-7 inhibit activities as can be seen from the table, almost active the same with contrast medicine 5-Fu; Compound (2) and (3) are best to HeLa inhibit activities, both activities elementary errors with contrast medicine 5-Fu; In table, listed compound is overall to BEL-7402 difference, only has the IC of compound (1) 50μM just reach 9.28.Such structure-activity result is challenging, but because whole problem is in the research and development initial stage, temporarily cannot overall texture effect relationship, but we can synthesize a large amount of derivatives of this class formation successively, and detailed correlative study result will be published in internal class core periodical.
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 (6)

1. there is an amides for anti-tumor activity, it is characterized in that: amides is as the salt of logical formula I, general formula (I) compound isomers or general formula (I) compound;
Wherein: R 1, R 2, R 3, R 4and R 5what may be the same or different is selected from hydrogen, halogen, cyano group, hydroxyl, haloalkyl, alkoxyl group, alkoxyalkyl, alkylamino radical or alkylamino radical alkyl; X is oxygen, sulphur, carbon or nitrogen-atoms.
2. by the amides with anti-tumor activity according to claim 1, it is characterized in that: described amides is compound (1), compound (2), compound (3), compound (4), compound (5) or compound (6), and concrete structure formula is as follows:
3. an application with the amides of anti-tumor activity according to claim 1, is characterized in that: described general formula (I) compound, its salt or isomer are for the preparation of anti-tumor drug.
4. by the application with the amides of anti-tumor activity according to claim 3, it is characterized in that: 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.
5. by the application with the amides of anti-tumor activity according to claim 4, it is characterized in that: the weight percentage of the active ingredient in described anti-tumor compositions is 30-80%.
6. by the application with the amides of anti-tumor activity according to claim 5, it is characterized in that: described anti-tumor compositions is tablet, capsule, powder, pill, granule or emulsion.
CN201510117809.7A 2015-03-17 2015-03-17 Amide compounds having antineoplastic activity and application thereof Pending CN104693182A (en)

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103755695A (en) * 2013-12-20 2014-04-30 陕西理工学院 Amide compounds with antitumor activity and application of amide compounds
CN103772374A (en) * 2014-02-24 2014-05-07 陕西理工学院 Novel heterocyclic compound and application thereof
CN103882262A (en) * 2014-02-26 2014-06-25 蚌埠市英路光电有限公司 Zinc-based aluminum alloy material for angle valve, and preparation method thereof

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103755695A (en) * 2013-12-20 2014-04-30 陕西理工学院 Amide compounds with antitumor activity and application of amide compounds
CN103772374A (en) * 2014-02-24 2014-05-07 陕西理工学院 Novel heterocyclic compound and application thereof
CN103882262A (en) * 2014-02-26 2014-06-25 蚌埠市英路光电有限公司 Zinc-based aluminum alloy material for angle valve, and preparation method thereof

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Application publication date: 20150610