CN103772374A - Novel heterocyclic compound and application thereof - Google Patents
Novel heterocyclic compound and application thereof Download PDFInfo
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- CN103772374A CN103772374A CN201410060585.6A CN201410060585A CN103772374A CN 103772374 A CN103772374 A CN 103772374A CN 201410060585 A CN201410060585 A CN 201410060585A CN 103772374 A CN103772374 A CN 103772374A
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- 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
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- 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
- C07D249/14—Nitrogen atoms
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- 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
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- 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
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Abstract
The invention belongs to the technical field of a medicine, and particularly relates to a novel heterocyclic compound and an application thereof. The heterocyclic compound is a compound in a general formula (I), an isomer of the compound in the general formula (I), or a salt of the compound in the general formula (I), wherein R1, R2 and R3 are hydrogen, cyan, hydroxyl, haloalkyl, alkoxy, lkoxysilane, alkoxy alkyl, alkyl amino alkyl or R4; X is C or N; M is O or S; and the R4 is substitutional carbonyl. The pharmacological activity screening result of the compound disclosed by the invention shows that that the novel heterocyclic compound has good inhibiting effects on MCF-7 (human breast cancer cell) HeLa (human cervical cancer cell) or BeL7402 (human hepatocellular carcinoma cell), and has good development and application prospects in the anti-tumor aspect. (img file= 'DDA0000468725720000011.TIF' wi= '488' he= '560' /).
Description
Technical field
The invention belongs to medical technical field, specifically a kind of new type heterocycle compounds and application thereof.
Background technology
Malignant tumour is a kind of common disease of serious threat human health, and the mortality ratio ranking the second that malignant tumour causes, is only second to cardiovascular disorder.According to incompletely statistics, the whole world has nearly new cases of 2,000 ten thousand every year.Updated statistics demonstration, the annual tumour new cases of China are about 2,200,000, because tumor mortality number is about 1,600,000, account for 1/5th of disease death number.At present mainly contain pharmacotherapy, operative therapy and radiotherapy for the treatment of tumour.Pharmacological agent has become the important means of current clinical cancer therapy.The antitumor drug of clinical main use roughly can be divided into the medicine (as: endoxan that destroys DNA structure and function, oxaliplatin etc.), the medicine that affects Nucleic acid is (as Fluracil, gemcitabine, methotrexate etc.), disturb transcription to suppress synthetic medicine (as Zorubicin), the antitumor antibiotics (as dactinomycin) etc. of RNA.Its pharmacological action is all " cytocide " substantially, thus they non-specifically block cell fission and cause necrocytosis, in killing tumour cell, also destroyed human normal cell.For the poor selectivity, the toxic side effect that overcome conventional cell cytotoxic drug more by force, easily produce the shortcomings such as resistance, antitumor drug is transitioned into according to the specific effect of clear and definite mechanism of action in the medicament research and development of dysfunction cell from the research of conventional cell cytotoxic drug.
Summary of the invention
The object of the present invention is to provide a kind of new type heterocycle compounds and application thereof.
For achieving the above object, the technical solution used in the present invention is:
A kind of new type heterocycle compounds, heterocyclic compound is as the salt of logical formula I, general formula (I) compound isomers or general formula (I) compound;
Wherein, R
1, R
2and R
3hydrogen, cyano group, hydroxyl, haloalkyl, alkoxyl group, alkoxyalkyl, alkylamino radical, alkylamino radical alkyl or R
4; X is C or N; M is O or S; Described R
4for the carbonyl replacing.
Described R
4for hydroxyl, halogen, alkyl, amino, haloalkyl, alkylthio alkyl, alkoxyalkyl or pyrimidyl replace or group as follows
or
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.
Described heterocyclic compound is compound (1), compound (2), compound (3), compound (4) or compound (5), and concrete structure formula is as follows:
An application for new type heterocycle compounds, 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 30-80%.
Described anti-tumor compositions is tablet, capsule, powder, pill, granule or emulsion.
The present invention has advantages of: 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
Compound (1) the H NMR collection of illustrative plates that Fig. 1 provides for the embodiment of the present invention;
Compound (2) the H NMR collection of illustrative plates that Fig. 2 provides for the embodiment of the present invention;
Compound (3) the H NMR collection of illustrative plates that Fig. 3 provides for the embodiment of the present invention;
Compound (4) the H NMR collection of illustrative plates that Fig. 4 provides for the embodiment of the present invention;
Compound (5) the H NMR collection of illustrative plates that Fig. 5 provides 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 indicate outside, raw materials used all have commercially available.
Heterocyclic compound obtains according to following synthetic route preparation.Specifically, take replacement time, contain nitro and hydrazine class compound as starting raw material, after (4-aminophenyl) oxo formyl chloride becomes acid amides reaction, dewater with triphenylphosphine condensation again, pass through again hydrogen, palladium/carbon was amino nitro ring originally, finally obtained finished product with the acyl chloride reaction replacing again.
Synthetic route general formula I
The present invention includes compound that above-mentioned general formula I comprises and be preparation composition that activeconstituents is mixed with and the preparation of preparation composition.Formulation preparation method for: 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 third two
The combination solvent of alcohol 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 when 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 difference for the treatment of, the usage difference of medicine; 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.; Can make the form of described salt if any the alkaline compound as amine and suitable acid; 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 product medicine becoming take compound in above-mentioned general formula I as active fraction preparation, 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.Use conventional method proportioning by technician, 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.
Embodiment 1: compound (1) synthetic
By (4-aminophenyl) oxo formyl chloride 1.6g (7.98mmol, 1.05equiv) be dissolved in 50mL round-bottomed flask with 10mL methylene dichloride, then nitrogen protection, stir and drip with 3 of 12mL methylene dichloride dissolving at 0 ℃, 4-xylidine 970mg (8.00mmol, 1.05equiv), continue after stir about 2h, in above-mentioned system, add N-ethyl-N-sec.-propyl propyl group-2-amine 1.47g (11.38mmol again, 1.50equiv) with 2-nitro-5-(piperidyl-1) benzoyl hydrazine 2.0g (7.26mmol, 1.00equiv, 96%), and 3h is stirred in continuation, reaction is finished, add the dilution of 100mL methylene dichloride, again respectively with saturated aqueous common salt and purified water washing, anhydrous sodium sulfate drying, concentrating under reduced pressure organic phase, finally adopt silica gel column chromatography separate mode to purify, eluent is petrol ether/ethyl acetate (4:1), obtain light yellow solid 4-(3, 4-3,5-dimethylphenyl)-1-(2-nitro-5-(piperidyl-1) benzoyl) Urea,amino-2.0g, productive rate 67%, (ES, m/z): 412.2[M+H]
+ 1, 414.2[M+H+2]
+ 1.
By upper step product 1.4g (3.40mmol, 1.00equiv) be placed in 250mL round-bottomed flask, add 1,2-ethylene dichloride 100mL, triphenylphosphine 1.34g (5.11mmol, 1.50equiv) with triethylamine 2.06g (20.36mmol, 6.00equiv), stirring at room temperature, the mixed solution of dropping 33mL tetrahydrofuran (THF)/tetracol phenixin=2:1, then whole system is risen to 85 ℃ of stirrings and spend the night, reaction is finished.Concentrating under reduced pressure organic phase, finally adopt silica gel column chromatography separate mode to purify, eluent is petrol ether/ethyl acetate (1:10-1:1), obtain light yellow solid 5-(2-amino-5-(piperidyl-1) phenyl)-N-(3,4-3,5-dimethylphenyl)-1,3,4-oxadiazole-2-amine 1.02g, productive rate 75%, (ES, m/z): 394.2[M+H]
+ 1, 396.2[M+H+2]
+ 1.
In 100mL round-bottomed flask, add and walk product 230mg (0.58mmol, 1.00equiv), palladium/carbon 0.03g and methyl alcohol 30mL, under liquid level, import hydrogen, stirring at room temperature 5h, and reaction is complete, filters, concentrating under reduced pressure organic phase, obtain light yellow crude product 5-(2-amino-5-(piperidyl-1) phenyl)-N-(3,4-3,5-dimethylphenyl)-1,3, the about 0.20g of 4-oxadiazole-2-amine, needn't purify and directly cast single step reaction.
By upper step product 800mg (1.98mmol, 1.00equiv, 100%) be dissolved in 100mL round-bottomed flask with 20mL methylene dichloride, pyridine-2-formyl chloride 70mg (0.49mmol 0 ℃ of dropping with the dilution of 20mL methylene dichloride, 1.20equiv), time for adding is about 30min and stirs and spend the night, reaction is finished, add again 20mL methylene dichloride dilute reaction solution, again respectively with saturated aqueous common salt and purified water washing, concentrating under reduced pressure, finally adopt silica gel column chromatography separate mode to purify, eluent is petrol ether/ethyl acetate (1:1), obtain shallow off-white color solid (1) 110mg, productive rate 46%, (ES, m/z): 469.2[M+H]
+ 1, 471.2[M+H+2]
+ 1.H NMR (300MHz, DMSO) δ: 12.87 (s, 1H), (9.17-9.14 d, J=9.3Hz, 1H), (8.85-8.84 d, J=4.2Hz, 1H), 8.34 (s, 1H), 8.28-8.26 (d, J=8.1Hz, 1H), 7.93-7.90 (m, 1H), 7.88 (s, 1H), (7.53-7.48 t, J=1.8Hz, 2H), (7.36-7.34 d, J=6.6Hz, 2H), (7.17-7.14 d, J=8.1Hz, 1H), 3.49 (m, 4H), 2.30-2.25 (m, 6H), 2.14 (m, 4H), 1.76 (m, 2H), are shown in Fig. 1.
Embodiment 2: compound (2) synthetic
Difference from Example 1 is, adopting 2-nitro-5-(piperidyl-1) benzoyl imines hydrazides is raw material, is synthetic route I according to the synthetic method of embodiment 1, can make compound (2), and concrete structure formula is as follows:
(ES, m/z): 508.2[M+H]
+ 1, 510.2[M+H+2]
+ 1; H NMR (300MHz, CDCl
3) δ: 11.78 (s, 1H), 9.82 (s, 1H), 8.72 (s, 1H), 8.31 (s, 1H), 8.16-8.14 (d, J=6.9Hz, 2H), 8.05-8.00 (t, 1H), 7.89-7.86 (d, J=7.5Hz, 1H), 7.59-7.17 (m, 5H), 3.32 (s, 4H), 1.73-1.61 (m, 6H), is shown in Fig. 2.
Embodiment 3: compound (3) synthetic
Difference from Example 1 is, adopting 2-nitro-5-(piperidines) benzoyl sulfydryl hydrazides is raw material, is synthetic route I according to the synthetic method of embodiment 1, can make compound (3), and concrete structure formula is as follows:
(ES, m/z): 525.2[M+H]
+ 1, 527.2[M+H+2]
+ 1; H NMR (300MHz, CDCl
3) δ: 11.69 (s, 1H), 8.842 (s, 1H), 8.46 (s, 1H), 8.16-8.14 (d, J=6.9Hz, 2H), 8.14-8.05 (t, 1H), 7.89-7.86 (d, J=7.5Hz, 1H), 7.61-7.22 (m, 5H), 3.31 (s, 4H), 1.73-1.61 (m, 6H), is shown in Fig. 3.
Embodiment 4: compound (4) synthetic
Adopt identical starting raw material with embodiment 1, but in the end become in acid amides reaction and adopt 3-((2-(ethylamino) ethylamino) methyl) Benzoyl chloride, be synthetic route I according to the synthetic method of embodiment 1 again, can make compound (4), concrete structure formula is as follows:
(ES, m/z): 635.2[M+H]
+ 1, 637.2[M+H+2]
+ 1; H NMR (300MHz, CDCl
3) δ: 9.05-9.02 (d, J=9.3Hz, 1H), 8.45 (s, 1H), 8.24-8.13 (m, 2H), 8.10-7.87 (m, 2H), 7.84-7.70 (m, 1H), 7.51-7.45 (m, 3H), 7.29-7.26 (d, J=7.8Hz, 1H), 3.98-3.95 (s, 2H), 3.72-3.64 (m, 4H), 3.45-3.41 (m, 2H), 3.26-3.19 (m, 5H), 3.12-3.08 (m, 2H), 2.52 (s, 3H), 2.08-2.06 (m, 4H), 1.86-1.85 (m, 2H), 1.37-1.29 (m, 7H), see Fig. 4.
Embodiment 5: compound (5) synthetic
Adopt identical starting raw material with embodiment 1, but in the end become in acid amides reaction and adopt 3-(((2-(ethylamino) ethyl) (methyl) amino) methyl) Benzoyl chloride, be synthetic route I according to the synthetic method of embodiment 1 again, can make compound (5), concrete structure formula is as follows:
(ES, m/z): 649.2[M+H]
+ 1, 651.2[M+H+2]
+ 1; H NMR (300MHz, CDCl
3) δ: 9.03-9.00 (d, J=9.0Hz, 1H), 8.40 (s, 1H), 8.10-8.05 (m, 2H), 7.90 (s, 1H), 7.84-7.81 (d, J=9.3Hz, 1H), 7.70-7.61 (m, 2H), 7.48-7.36 (m, 2H), (7.27-7.25 d, J=7.5Hz, 1H), 3.81 (s, 2H), 3.69-3.65 (m, 4H), 3.20-3.08 (m, 4H), 2.95-2.93 (m, 2H), 2.44 (s, 3H), 2.06-2.04 (d, J=4.8Hz, 4H), 1.83 (s, 2H), 1.3-1.25 (m, 6H), is shown in Fig. 5.
Embodiment 6: compound pharmacological evaluation
Testing compound is to MCF-7 (human breast cancer cell), and HeLa (human cervical carcinoma cell) and BeL7402 (human liver cancer cell) tumour cell, as research object, adopt tetramethyl-azo azoles salt colorimetry, i.e. mtt assay.Active in half-inhibition concentration (IC
50) represent, unit is μ M, take 5 FU 5 fluorouracil as contrast medicine.
Take MCF-7 cell as example:
Get the MCF-7 cell of 0.25% tryptic digestion monolayer culture, use containing the RPMI1640 nutrient solution of 10% foetal calf serum and 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 CO2 incubator, 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.Continue at CO
2in incubator in 37 ℃, 5%CO
2under condition, cultivate 72h.Every hole adds 20 μ L MTT solution (5mg/mL), continue to hatch 4h in 37 ℃, 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.
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 new type heterocycle compounds, is characterized in that: heterocyclic compound is as the salt of logical formula I, general formula (I) compound isomers or general formula (I) compound;
Wherein, R
1, R
2and R
3hydrogen, cyano group, hydroxyl, haloalkyl, alkoxyl group, alkoxyalkyl, alkylamino radical, alkylamino radical alkyl or R
4; X is C or N; M is O or S; Described R
4for the carbonyl replacing.
2. by new type heterocycle compounds claimed in claim 1, it is characterized in that:
Described R
4for hydroxyl, halogen, alkyl, amino, haloalkyl, alkylthio alkyl, alkoxyalkyl or pyrimidyl replace or group as follows
or
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 new type heterocycle compounds claimed in claim 1, it is characterized in that: described heterocyclic compound is compound (1), compound (2), compound (3), compound (4) or compound (5), and concrete structure formula is as follows:
4. an application for new type heterocycle compounds 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 new type heterocycle compounds 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 new type heterocycle compounds claimed in claim 5, it is characterized in that: the weight percentage of the active ingredient in described anti-tumor compositions is 30-80%.
7. by the application of new type heterocycle compounds 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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|---|---|---|---|---|
| CN104693182A (en) * | 2015-03-17 | 2015-06-10 | 陕西理工学院 | Amide compounds having antineoplastic activity and application thereof |
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| WO2005004818A2 (en) * | 2003-07-09 | 2005-01-20 | Imclone Systems Incorporated | Heterocyclic compounds and their use as anticancer agents |
| CN103755695A (en) * | 2013-12-20 | 2014-04-30 | 陕西理工学院 | Amide compounds with antitumor activity and application of amide compounds |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005004818A2 (en) * | 2003-07-09 | 2005-01-20 | Imclone Systems Incorporated | Heterocyclic compounds and their use as anticancer agents |
| CN103755695A (en) * | 2013-12-20 | 2014-04-30 | 陕西理工学院 | Amide compounds with antitumor activity and application of amide compounds |
Non-Patent Citations (1)
| Title |
|---|
| PEDRO MOLINA，等: "Preparation of 2-Substituted 1,3,4-Thiadiazoles and Mesoionic 1,3,4-Thiadiazole[3,2-c]quinazolines from 4H-3,1-Benzothiazine-4-thiones or 3-Amino-4(3H)-quinazolinethioness", 《LIEBIGS ANN. CHEM.》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104693182A (en) * | 2015-03-17 | 2015-06-10 | 陕西理工学院 | Amide compounds having antineoplastic activity and application thereof |
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