CN106496108A - There is amides compound and its application of anti-tumor activity - Google Patents

There is amides compound and its application of anti-tumor activity Download PDF

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CN106496108A
CN106496108A CN201610935136.0A CN201610935136A CN106496108A CN 106496108 A CN106496108 A CN 106496108A CN 201610935136 A CN201610935136 A CN 201610935136A CN 106496108 A CN106496108 A CN 106496108A
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amides compound
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CN106496108B (en
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姚志艺
王庆宣
舒启胜
薛楠楠
杨燕
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Shanghai Institute of Technology
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
    • C07D213/72—Nitrogen atoms
    • C07D213/75—Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C233/00—Carboxylic acid amides
    • C07C233/64—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings
    • C07C233/65—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
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    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C233/00—Carboxylic acid amides
    • C07C233/64—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings
    • C07C233/66—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by halogen atoms or by nitro or nitroso groups
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    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C233/00—Carboxylic acid amides
    • C07C233/64—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings
    • C07C233/67—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms
    • C07C233/75—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a six-membered aromatic ring
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    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
    • C07C235/42—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton
    • C07C235/44—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton with carbon atoms of carboxamide groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring
    • C07C235/56—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton with carbon atoms of carboxamide groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a six-membered aromatic ring
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
    • C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or 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
    • C07D307/58—One oxygen atom, e.g. butenolide
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
    • C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
    • C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom 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
    • C07D333/38—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur 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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Abstract

The invention belongs to field of pharmaceutical chemistry technology, specially a kind of amides compound and its application with anti-tumor activity.The structural formula R of the amides compound of the present invention1CONHR2Represent, wherein R1、R2Independently selected from aromatic radical or heterocycle.The biological activity test result of the compounds of this invention shows that such compound has good inhibiting effect to histone methyl SET7.The application prospect that there is good anti-tumor aspect to develop.

Description

There is amides compound and its application of anti-tumor activity
Technical field
The present invention relates to a class has the amides compound of anti-tumor activity and its application, belong to pharmaceutical chemistry technology neck Domain.
Technical background
With the continuous development of medicine and pharmacology, people achieve achievement obvious to all for the treatment of numerous disease.Cancer These diseases, are nowadays still a great problem for perplexing medical circle.For the research of antitumor drug is carried out in high gear.
Tumor becomes the second killer for threatening human life, dies from every year on average pernicious in more than 50 hundred million population of the whole world Up to 6,900,000 people, new case is 8,700,000 to tumor person, and the number is also increasing year by year.Therefore, national governments, research institution and system Medicine company is paid much attention to tumor research and antitumor drug for a long time always, in antitumor drug research and development, at present Achieved with major progress.
In recent years, molecular biology, molecular pharmacology, the development of oncology make tumor essence progressively illustrate；Big rule The invention of the advanced technologies such as mould rapid screening, combinatorial chemistry, genetic engineering and application acceleration drug development process；Antineoplastic agent The research and development of thing have been enter into brand-new epoch.
The new antitumoral medicine that antitumor drug is just being acted on from traditional cytotoxic drug to the too many levels for mechanism Thing develops.Antitumor drug new development in recent years, including cytotoxic anti-tumor drug, with cellular signal transduction molecule as target spot Antitumor drug, angiogensis inhibitor, tumor drug resistance reversal agent, the swift and violent of the life sciences such as endocrine therapy medicine send out Exhibition, the successfully understanding deep to tumor and the new opportunity of prevention generation.
As to the continuous research of antitumor drug and developing rapidly for oncobiology, people gradually recognize that cell is sent out The essence of raw canceration is Cell signal propagation pathways imbalance, so as to cause the unlimited hypertrophy of cell.Research and development focus is also just from tradition Cell toxicity medicament is turned to for numerous targeting links during tumor development.These target spot new drugs are directed to normal cell and swell Difference between oncocyte, can overcome that the poor selectivity of conventional cell cytotoxic drug, toxic and side effects are strong, be also easy to produce drug resistance etc. lacks Point, can reach high selectivity and hypotoxic therapeutic effect.Thus, antitumor drug enter a brand-new development- The research of anti-tumor drugs targeting.But new type antineoplastic medicine research and development to reach real cure tumor and also need to one overflow Long process.The invention provides a kind of have the new amide-type medicines structure of targeting anti-tumor activity, it is with histone methyl The compound for having biological activity screened for target spot by SET7.There is important development prospect.
Content of the invention
It is an object of the invention to provide a kind of amides compound and its application with anti-tumor activity.
For achieving the above object, the technical solution used in the present invention is specific as follows.
There is the amides compound of anti-tumor activity, the structure such as formula of amides compound（Ⅰ）Shown；
Wherein：R1、R2Independently selected from aromatic radical or heterocyclic radical.
In the present invention, aromatic radical is phenyl that is unsubstituted or replacing；Heterocyclic radical is oxygen-containing selected from unsubstituted or replacement In heterocyclic radical, sulfur heterocyclic ring base or nitrogen heterocycle any one.Substituent group is monosubstituted, two replacements or three replacements, replaces One or more in halogen, nitro, methoxyl group, methyl or trifluoromethyl of base independence.Unsubstituted or replace contain Oxa- ring group, sulfur heterocyclic ring base and or nitrogen heterocycle be five yuan or hexa-member heterocycle.
In the present invention, heterocyclic radical is pyridine radicals that are unsubstituted or replacing, furan ring group or thienyl, and substituent group is single Replacement, two replacements or three replacements, one kind in halogen, nitro, methoxyl group, methyl or trifluoromethyl of substituent group independence Or it is several.
The present invention also provides a kind of above-mentioned amides compound with anti-tumor activity as histone methyl SET7 Inhibitor, prepare treatment, prevention, alleviate tumor antitumor drug in application.
In the present invention, the antitumor drug is the medicine for treating, prevent or alleviating breast carcinoma, cervical cancer or hepatocarcinoma.
In the present invention, the weight percent content of the active component in described antitumor drug is 25-80%.
In the present invention, described antitumor drug is tablet, capsule, powder, pill, granule or Emulsion
Compared to the prior art, the device have the advantages that as follows：The amides compound that the present invention is provided is biological Activity Results show which has good inhibitory action to histone methyl SET7.
Specific embodiment
The amides compound and biological activity of the present invention are described further with reference to example is embodied as, but Protection scope of the present invention is not limited to that.
Embodiment 1
50ml single port bottles are taken, is sequentially added in the triethylamine of 7ml anhydrous methylene chlorides, 0.335ml, and 0.1g following formulas B1, it is stirred to dissolve, under ice bath, Deca is dissolved with 0.164gA1Dichloromethane solution, room temperature magnetic agitation 8h react.Reaction knot Shu Hou, is washed three times with saturated common salt, anhydrous sodium sulfate drying organic faciess 1 hour.Crossing silicagel column petroleum ether than ethyl acetate is 5:1 separates, that is, obtain following formula: compound, yield 68%, purity 95%（HPLC）.Afterwards its biological activity is tested.
Net reaction is as follows：
Mass spectrometric data：MS m/z：259.10（M+1,100）.Nuclear magnetic data：1H NMR(501MHz,DMSO)δ9.21(s, 1H),8.09(d,J=8.7Hz,1H),7.96(d,J=8.3Hz,2H),7.24–6.83(m,3H),6.38(d,J=9.7Hz,1H), 3.83(s,3H),3.78(s,3H).
Embodiment 2
50ml single port bottles are taken, is sequentially added in the triethylamine of 7ml anhydrous methylene chlorides, 0.273ml, and 0.1g following formulas B2, it is stirred to dissolve, under ice bath, Deca is dissolved with 0.134gA1Dichloromethane solution, room temperature magnetic agitation 8h react.Reaction knot Shu Hou, is washed three times with saturated common salt, anhydrous sodium sulfate drying organic faciess 1 hour.Crossing silicagel column petroleum ether than ethyl acetate is 5:1 separates, that is, obtain following formula: compound, yield 62%, purity 94%（HPLC）.Afterwards its biological activity is tested.
Net reaction is as follows:
Mass spectrometric data：MS m/z：287.10（M+1,100）.Nuclear magnetic data：1H NMR(501MHz,DMSO)δ9.62(s, 1H),7.95(d,J=8.7Hz,2H),7.68–6.84(m,5H),3.81(s,3H),2.12(s,3H).
Embodiment 3
50ml single port bottles are taken, is sequentially added in the triethylamine of 7ml anhydrous methylene chlorides, 0.303ml, and 0.1g following formulas B3, it is stirred to dissolve, under ice bath, Deca is dissolved with 0.149gA1Dichloromethane solution, room temperature magnetic agitation 8h react.Reaction knot Shu Hou, is washed three times with saturated common salt, anhydrous sodium sulfate drying organic faciess 1 hour.Crossing silicagel column petroleum ether than ethyl acetate is 5:1 separates, that is, obtain following formula: compound, yield 65%, purity 94%（HPLC）.Afterwards its biological activity is tested.
Net reaction is as follows:
Mass spectrometric data：MS m/z：272.12（M+1,100）.Nuclear magnetic data：1H NMR(501MHz,DMSO)δ9.79(s, 1H),8.12(s,1H),7.92(d,J=8.7Hz,2H),7.06-6.85(d,J=8.1Hz,4H),8.85(s,3H),2.26(s, 3H).
Embodiment 4
50ml single port bottles are taken, the B in the triethylamine of 7ml anhydrous methylene chlorides, 0.271g, and 0.1g following formulas is sequentially added4, It is stirred to dissolve, under ice bath, Deca is dissolved with 0.228gA1Dichloromethane solution, room temperature magnetic agitation 8h react.Reaction terminates Afterwards, washed three times with saturated common salt, anhydrous sodium sulfate drying organic faciess 1 hour.It is 5 that silicagel column petroleum ether is crossed than ethyl acetate:1 Separate, that is, obtain following formula: compound, yield 80%, purity 94%（HPLC）.Afterwards its biological activity is tested.
Net reaction is as follows:
Mass spectrometric data：MS m/z：246.09（M+1,100）.Nuclear magnetic data：1H NMR(501MHz,DMSO)δ10.38(s, 1H),7.98(d,J=8.7Hz,2H),7.60(d,J=8.1Hz,2H),7.15(d,J=9.2Hz,2H),7.60(d,J=8.6Hz, 2H),3.85(s,3H).
Embodiment 5
50ml single port bottles are taken, the B in the triethylamine of 7ml anhydrous methylene chlorides, 0.188g, and 0.1g following formulas is sequentially added5, It is stirred to dissolve, under ice bath, Deca is dissolved with 0.159gA1Dichloromethane solution, room temperature magnetic agitation 8h react.Reaction terminates Afterwards, washed three times with saturated common salt, anhydrous sodium sulfate drying organic faciess 1 hour.It is 5 that silicagel column petroleum ether is crossed than ethyl acetate:1 Separate, that is, obtain following formula: compound, yield 86%, purity 96%（HPLC）.Afterwards its biological activity is tested.
Net reaction is as follows:
Mass spectrometric data：MS m/z：296.08（M+1,100）.Nuclear magnetic data：1H NMR(501MHz,DMSO)δ10.4(s, 1H),7.96(t,J=8.7Hz,2H),7.57-7.46(d,J=8.1Hz,4H),,7.10(d,J=7.2Hz,2H),3.81(s, 3H).
Embodiment 6
50ml single port bottles are taken, the B in the triethylamine of 7ml anhydrous methylene chlorides, 0.244g, and 0.1g following formulas is sequentially added1, It is stirred to dissolve, under ice bath, Deca is dissolved with 0.157gA2Dichloromethane solution, room temperature magnetic agitation 8h react.Reaction terminates Afterwards, washed three times with saturated common salt, anhydrous sodium sulfate drying organic faciess 1 hour.It is 5 that silicagel column petroleum ether is crossed than ethyl acetate:1 Separate, that is, obtain following formula: compound, yield 79%, purity 95%（HPLC）.Afterwards its biological activity is tested.
Net reaction is as follows:
Mass spectrometric data：MS m/z：219.07（M+1,100）.Nuclear magnetic data：1H NMR(501MHz,DMSO)δ10.17(s, 1H),7.94(s,1H),7.75(d,J=7.8Hz,2H),7.34(dd,J=9.6,6.0Hz,3H),7.10(t,J=7.4Hz,1H), 6.86–6.61(m,1H),5.76(s,1H),4.11(q,J=5.3Hz,1H),2.51(s,3H).
Embodiment 7
50ml single port bottles are taken, the B in the triethylamine of 7ml anhydrous methylene chlorides, 0.30ml, and 0.1g following formulas is sequentially added3, It is stirred to dissolve, under ice bath, Deca is dissolved with 0.150gA2Dichloromethane solution, room temperature magnetic agitation 8h react.Reaction terminates Afterwards, washed three times with saturated common salt, anhydrous sodium sulfate drying organic faciess 1 hour.It is 5 that silicagel column petroleum ether is crossed than ethyl acetate:1 Separate, that is, obtain following formula: compound, yield 83%, purity 94%（HPLC）.Afterwards its biological activity is tested.
Net reaction is as follows:
Mass spectrometric data：MS m/z：232.09（M+1,100）.Nuclear magnetic data：1H NMR(501MHz,DMSO)δ10.17(s, 1H),7.94(s,1H),7.34(dd,J=9.6,6.0Hz,1H),7.10(t,J=7.4Hz,1H),6.86–6.61(m,1H), 5.76(s,1H),4.11(q,J=5.3Hz,1H),3.34(s,2H),3.17(d,J=5.2Hz,1H),2.51(s,3H).
Embodiment 8
50ml single port bottles are taken, the B in the triethylamine of 7ml anhydrous methylene chlorides, 0.391g, and 0.1g following formulas is sequentially added6, It is stirred to dissolve, under ice bath, Deca is dissolved with 0.252gA2Dichloromethane solution, room temperature magnetic agitation 8h react.Reaction terminates Afterwards, washed three times with saturated common salt, anhydrous sodium sulfate drying organic faciess 1 hour.It is 5 that silicagel column petroleum ether is crossed than ethyl acetate:1 Separate, that is, obtain following formula: compound, yield 88%, purity 94%（HPLC）.Afterwards its biological activity is tested.
Net reaction is as follows:
Mass spectrometric data：MS m/z：188.06（M+1,100）.Nuclear magnetic data：1H NMR(501MHz,DMSO)δ10.17(s, 1H),7.75(d,J=7.8Hz,2H),7.34(dd,J=9.6,6.0Hz,3H),7.10(t,J=7.4Hz,1H),4.11(q,J= 5.3Hz,1H),3.17(d,J=5.2Hz,1H).
Embodiment 9
50ml single port bottles are taken, the B in the triethylamine of 7ml anhydrous methylene chlorides, 0.244g, and 0.1g following formulas is sequentially added1, It is stirred to dissolve, under ice bath, Deca is dissolved with 0.213gA3Dichloromethane solution, room temperature magnetic agitation 8h react.Reaction terminates Afterwards, washed three times with saturated common salt, anhydrous sodium sulfate drying organic faciess 1 hour.It is 5 that silicagel column petroleum ether is crossed than ethyl acetate:1 Separate, that is, obtain following formula: compound, yield 89%, purity 94%（HPLC）.Afterwards its biological activity is tested.
Net reaction is as follows:
Mass spectrometric data：MS m/z：265.07（M+1,100）.Nuclear magnetic data：1H NMR(501MHz,DMSO)δ9.94(s, 1H),8.12(d,J=6.8Hz,1H),7.93-7.04(d,J=12.6Hz,3H),6.38(m,J=10.0Hz,1H),3.83(s, 3H).
Embodiment 10
50ml single port bottles are taken, the B in the triethylamine of 7ml anhydrous methylene chlorides, 0.221g, and 0.1g following formulas is sequentially added3, It is stirred to dissolve, under ice bath, Deca is dissolved with 0.193gA3Dichloromethane solution, room temperature magnetic agitation 8h react.Reaction terminates Afterwards, washed three times with saturated common salt, anhydrous sodium sulfate drying organic faciess 1 hour.It is 5 that silicagel column petroleum ether is crossed than ethyl acetate:1 Separate, that is, obtain following formula: compound, yield 98%, purity 94%（HPLC）.Afterwards its biological activity is tested.
Net reaction is as follows:
Mass spectrometric data：MS m/z：278.09（M+1,100）.Nuclear magnetic data：1H NMR(501MHz,DMSO)δ9.79(s, 1H),8.32(s,1H),7.95-6.89(m,J=10.2Hz,4H),6.85(s,1H),6 3.83(s,3H),2.27(s,3H).
Embodiment 11
50ml single port bottles are taken, the B in the triethylamine of 7ml anhydrous methylene chlorides, 0.271g, and 0.1g following formulas is sequentially added4, It is stirred to dissolve, under ice bath, Deca is dissolved with 0.236gA3Dichloromethane solution, room temperature magnetic agitation 8h react.Reaction terminates Afterwards, washed three times with saturated common salt, anhydrous sodium sulfate drying organic faciess 1 hour.It is 5 that silicagel column petroleum ether is crossed than ethyl acetate:1 Separate, that is, obtain following formula: compound, yield 76%, purity 93%（HPLC）.Afterwards its biological activity is tested.
Net reaction is as follows:
Mass spectrometric data：MS m/z：253.05（M+1,100）.Nuclear magnetic data：1H NMR(501MHz,DMSO)δ10.28(s, 1H),8.49(d,J=10.2Hz,1H),7.96-7.24(m,J=7.9Hz,3H),6.86(s,1H).
Embodiment 12
50ml single port bottles are taken, the B in the triethylamine of 7ml anhydrous methylene chlorides, 0.207g, and 0.1g following formulas is sequentially added5, It is stirred to dissolve, under ice bath, Deca is dissolved with 0.180gA3Dichloromethane solution, room temperature magnetic agitation 8h react.Reaction terminates Afterwards, washed three times with saturated common salt, anhydrous sodium sulfate drying organic faciess 1 hour.It is 5 that silicagel column petroleum ether is crossed than ethyl acetate:1 Separate, that is, obtain following formula: compound, yield 82%, purity 96%（HPLC）.Afterwards its biological activity is tested.
Net reaction is as follows:
Mass spectrometric data：MS m/z：302.05（M+1,100）.Nuclear magnetic data：1H NMR(501MHz,DMSO)δ10.32(s, 1H),7.95(d,J=10.2Hz,1H),7.52(d,J=7.9Hz,2H),7.46-7.24(d,J=17.3,8.3Hz,3H),6.85 (s,1H).
Embodiment 13
50ml single port bottles are taken, the B in the triethylamine of 7ml anhydrous methylene chlorides, 0.326g, and 0.1g following formulas is sequentially added6, It is stirred to dissolve, under ice bath, Deca is dissolved with 0.284gA3Dichloromethane solution, room temperature magnetic agitation 8h react.Reaction terminates Afterwards, washed three times with saturated common salt, anhydrous sodium sulfate drying organic faciess 1 hour.It is 5 that silicagel column petroleum ether is crossed than ethyl acetate:1 Separate, that is, obtain following formula: compound, yield 73%, purity 94%（HPLC）.Afterwards its biological activity is tested.
Net reaction is as follows:
Mass spectrometric data：MS m/z：234.07（M+1,100）.Nuclear magnetic data：1H NMR(501MHz,DMSO)δ10.32(s, 1H),7.95(d,J=7.9Hz,1H),7.70(d,J=10.2Hz,2H),7.35-6.97(m,J=17.3,8.3Hz,4H),6.86 (s,1H).
Embodiment 14
50ml single port bottles are taken, the B in the triethylamine of 7ml anhydrous methylene chlorides, 0.244g, and 0.1g following formulas is sequentially added1, It is stirred to dissolve, under ice bath, Deca is dissolved with 0.253gA4Dichloromethane solution, room temperature magnetic agitation 8h react.Reaction terminates Afterwards, washed three times with saturated common salt, anhydrous sodium sulfate drying organic faciess 1 hour.It is 5 that silicagel column petroleum ether is crossed than ethyl acetate:1 Separate, that is, obtain following formula: compound, yield 91%, purity 94%（HPLC）.Afterwards its biological activity is tested.
Net reaction is as follows:
Mass spectrometric data：MS m/z：297.01（M+1,100）.Nuclear magnetic data：1H NMR(501MHz,DMSO)δ10.21(s, 1H),8.16(s,1H),8.09(d,J=10.2Hz,1H),7.78-7.62(m,J=7.9Hz,2H),7.05(d,J=7.8Hz, 1H),6.38(m,J=9.1Hz,1H),3.82(s,3H).
Embodiment 15
50ml single port bottles are taken, the B in the triethylamine of 7ml anhydrous methylene chlorides, 0.221g, and 0.1g following formulas is sequentially added3, It is stirred to dissolve, under ice bath, Deca is dissolved with 0.229gA4Dichloromethane solution, room temperature magnetic agitation 8h react.Reaction terminates Afterwards, washed three times with saturated common salt, anhydrous sodium sulfate drying organic faciess 1 hour.It is 5 that silicagel column petroleum ether is crossed than ethyl acetate:1 Separate, that is, obtain following formula: compound, yield 92%, purity 98%（HPLC）.Afterwards its biological activity is tested.
Net reaction is as follows:
Mass spectrometric data：MS m/z：310.03（M+1,100）.Nuclear magnetic data：1H NMR(501MHz,DMSO)δ9.79(s, 1H),8.32(s,1H),8.16(s,1H),7.78-7.62(d,J=8.1Hz,2H),7.05-6.95(d,J=7.8Hz,2H), 3.82(s,3H,2.28(s,3H).
Embodiment 16
50ml single port bottles are taken, the B in the triethylamine of 7ml anhydrous methylene chlorides, 0.271g, and 0.1g following formulas is sequentially added4, It is stirred to dissolve, under ice bath, Deca is dissolved with 0.280gA4Dichloromethane solution, room temperature magnetic agitation 8h react.Reaction terminates Afterwards, washed three times with saturated common salt, anhydrous sodium sulfate drying organic faciess 1 hour.It is 5 that silicagel column petroleum ether is crossed than ethyl acetate:1 Separate, that is, obtain following formula: compound, yield 90%, purity 94%（HPLC）.Afterwards its activity is tested.
Net reaction is as follows:
Mass spectrometric data：MS m/z：284.99（M+1,100）.Nuclear magnetic data：1H NMR(501MHz,DMSO)δ10.36(s, 1H),8.49(d,J=8.7Hz,1H),8.16(s,1H),7.95(s,1H),7.78-7.34(d,J=8.1Hz,3H).
Embodiment 17
50ml single port bottles are taken, the B in the triethylamine of 7ml anhydrous methylene chlorides, 0.188g, and 0.1g following formulas is sequentially added5, It is stirred to dissolve, under ice bath, Deca is dissolved with 0.195gA4Dichloromethane solution, room temperature magnetic agitation 8h react.Reaction terminates Afterwards, washed three times with saturated common salt, anhydrous sodium sulfate drying organic faciess 1 hour.It is 5 that silicagel column petroleum ether is crossed than ethyl acetate:1 Separate, that is, obtain following formula: compound, yield 79%, purity 94%（HPLC）.Afterwards its activity is tested.
Net reaction is as follows:
Mass spectrometric data：MS m/z：333.99（M+1,100）.Nuclear magnetic data：1H NMR(501MHz,DMSO)δ10.20(s, 1H),8.16(s,1H),7.81(dd,J=9.7Hz,2H),7.61-7.34(m,J=7.9Hz,4H).
Embodiment 18
50ml single port bottles are taken, is sequentially added in the triethylamine of 7ml anhydrous methylene chlorides, 0.273ml, and 0.1g following formulas B2, it is stirred to dissolve, under ice bath, Deca is dissolved with 0.134gA1Dichloromethane solution, room temperature magnetic agitation 8h react.Reaction knot Shu Hou, is washed three times with saturated common salt, anhydrous sodium sulfate drying organic faciess 1 hour.Crossing silicagel column petroleum ether than ethyl acetate is 5:1 separates, that is, obtain following formula: compound, yield 62%, purity 97%（HPLC）.Afterwards its biological activity is tested.
Net reaction is as follows:
Mass spectrometric data：MS m/z：266.01（M+1,100）.Nuclear magnetic data：1H NMR(501MHz,DMSO)δ10.56(s, 1H),8.16(s,1H),7.70(m,J=8.7Hz,4H),7.61-7.07(m,J=7.6Hz,3H).
Embodiment 19
50ml single port bottles are taken, the B in the triethylamine of 7ml anhydrous methylene chlorides, 0.244g, and 0.1g following formulas is sequentially added1, It is stirred to dissolve, under ice bath, Deca is dissolved with 0.287gA5Dichloromethane solution, room temperature magnetic agitation 8h react.Reaction terminates Afterwards, washed three times with saturated common salt, anhydrous sodium sulfate drying organic faciess 1 hour.It is 5 that silicagel column petroleum ether is crossed than ethyl acetate:1 Separate, that is, obtain following formula: compound, yield 95%, purity 94%（HPLC）.Afterwards its biological activity is tested.
Net reaction is as follows:
Mass spectrometric data：MS m/z：324.99（M+1,100）.Nuclear magnetic data：1H NMR(501MHz,DMSO)δ10.21(s, 1H),8.09(d,J=8.1Hz,1H),7.86-7.57(m,J=9.1Hz,3H),7.05(d,J=7.6Hz,1H),3.83(s,3H).
Embodiment 20
50ml single port bottles are taken, the B in the triethylamine of 7ml anhydrous methylene chlorides, 0.221g, and 0.1g following formulas is sequentially added3, It is stirred to dissolve, under ice bath, Deca is dissolved with 0.260gA5Dichloromethane solution, room temperature magnetic agitation 8h react.Reaction terminates Afterwards, washed three times with saturated common salt, anhydrous sodium sulfate drying organic faciess 1 hour.It is 5 that silicagel column petroleum ether is crossed than ethyl acetate:1 Separate, that is, obtain following formula: compound, yield 99%, purity 94%（HPLC）.Afterwards its biological activity is tested.
Net reaction is as follows:
Mass spectrometric data：MS m/z：338.01（M+1,100）.Nuclear magnetic data：1H NMR(501MHz,DMSO)δ9.79(s, 1H),8.32(s,1H),8.09(d,J=10.2Hz,1H),7.86-7.57(m,J=9.7Hz,3H),7.05(d,J=7.6Hz, 1H),3.85(s,3H),2.27(s,3H).
Embodiment 21
50ml single port bottles are taken, the B in the triethylamine of 7ml anhydrous methylene chlorides, 0.358g, and 0.1g following formulas is sequentially added6, It is stirred to dissolve, under ice bath, Deca is dissolved with 0.250gA5Dichloromethane solution, room temperature magnetic agitation 8h react.Reaction terminates Afterwards, washed three times with saturated common salt, anhydrous sodium sulfate drying organic faciess 1 hour.It is 5 that silicagel column petroleum ether is crossed than ethyl acetate:1 Separate, that is, obtain following formula: compound, yield 75%, purity 92%（HPLC）.Afterwards its biological activity is tested.
Net reaction is as follows:
Mass spectrometric data：MS m/z：293.99（M+1,100）.Nuclear magnetic data：1H NMR(501MHz,DMSO)δ10.32(s, 1H),7.86-7.56(m,J=9.6Hz,5H),7.32-7.06(m,J=8.7Hz,3H).
Embodiment 22
50ml single port bottles are taken, the B in the triethylamine of 7ml anhydrous methylene chlorides, 0.244g, and 0.1g following formulas is sequentially added1, It is stirred to dissolve, under ice bath, Deca is dissolved with 0.252gA6Dichloromethane solution, room temperature magnetic agitation 8h react.Reaction terminates Afterwards, washed three times with saturated common salt, anhydrous sodium sulfate drying organic faciess 1 hour.It is 5 that silicagel column petroleum ether is crossed than ethyl acetate:1 Separate, that is, obtain following formula: compound, yield 79%, purity 94%（HPLC）.Afterwards its biological activity is tested.
Net reaction is as follows:
Mass spectrometric data：MS m/z：297.08（M+1,100）.Nuclear magnetic data：1H NMR(501MHz,DMSO)δ10.21(s, 1H),8.09(s,1H),7.82(dd,J=8.2Hz,2H),7.65(d,J=8.7Hz,2H)7.05(d,J=7.6Hz,1H),6.38 (dd,J=10.7Hz,1H),3.85(s,3H).
Embodiment 23
50ml single port bottles are taken, the B in the triethylamine of 7ml anhydrous methylene chlorides, 0.221g, and 0.1g following formulas is sequentially added3, It is stirred to dissolve, under ice bath, Deca is dissolved with 0.228gA6Dichloromethane solution, room temperature magnetic agitation 8h react.Reaction terminates Afterwards, washed three times with saturated common salt, anhydrous sodium sulfate drying organic faciess 1 hour.It is 5 that silicagel column petroleum ether is crossed than ethyl acetate:1 Separate, that is, obtain following formula: compound, yield 75%, purity 94%（HPLC）.Afterwards its biological activity is tested.
Net reaction is as follows:
Mass spectrometric data：MS m/z：310.10（M+1,100）.Nuclear magnetic data：1H NMR(501MHz,DMSO)δ9.82(s, 1H),8.34(s,1H),7.82(dd,J=8.1Hz,2H),7.65(d,J=8.7Hz,2H)7.05(dd,J=7.6Hz,2H),3.85 (s,3H),2.27(s,3H).
Embodiment 24
50ml single port bottles are taken, the B in the triethylamine of 7ml anhydrous methylene chlorides, 0.271g, and 0.1g following formulas is sequentially added4, It is stirred to dissolve, under ice bath, Deca is dissolved with 0.134gA6Dichloromethane solution, room temperature magnetic agitation 8h react.Reaction terminates Afterwards, washed three times with saturated common salt, anhydrous sodium sulfate drying organic faciess 1 hour.It is 5 that silicagel column petroleum ether is crossed than ethyl acetate:1 Separate, that is, obtain following formula: compound, yield 83%, purity 96%（HPLC）.Afterwards its biological activity is tested.
Net reaction is as follows:
Mass spectrometric data：MS m/z：285.06（M+1,100）.Nuclear magnetic data：1H NMR(501MHz,DMSO)δ10.37(s, 1H),8.49(d,J=7.5Hz,1H),7.95-7.34(m,J=9.7Hz,6H).
Embodiment 25
50ml single port bottles are taken, the B in the triethylamine of 7ml anhydrous methylene chlorides, 0.188g, and 0.1g following formulas is sequentially added5, It is stirred to dissolve, under ice bath, Deca is dissolved with 0.194gA6Dichloromethane solution, room temperature magnetic agitation 8h react.Reaction terminates Afterwards, washed three times with saturated common salt, anhydrous sodium sulfate drying organic faciess 1 hour.It is 5 that silicagel column petroleum ether is crossed than ethyl acetate:1 Separate, that is, obtain following formula: compound, yield 91%, purity 94%（HPLC）.Afterwards its biological activity is tested.
Net reaction is as follows:
Mass spectrometric data：MS m/z：334.06（M+1,100）.Nuclear magnetic data：1H NMR(501MHz,DMSO)δ10.04(s, 1H),7.82(dd,J=7.6Hz,2H),7.65-7.54(m,J=10.7Hz,6H).
Embodiment 26
50ml single port bottles are taken, is sequentially added in the triethylamine of 7ml anhydrous methylene chlorides, 0.424g, and 0.13g following formulas B6, it is stirred to dissolve, under ice bath, Deca is dissolved with 0.437gA6Dichloromethane solution, room temperature magnetic agitation 8h react.Reaction knot Shu Hou, is washed three times with saturated common salt, anhydrous sodium sulfate drying organic faciess 1 hour.Crossing silicagel column petroleum ether than ethyl acetate is 5:1 separates, that is, obtain following formula: compound, yield 71%, purity 94%（HPLC）.Afterwards its biological activity is tested.
Net reaction is as follows:
Mass spectrometric data：MS m/z：266.07（M+1,100）.Nuclear magnetic data：1H NMR(501MHz,DMSO)δ10.20(s, 1H),7.82(dd,J=7.6Hz,2H),7.70-7.65(m,J=10.8Hz,4H)7.35-7.01(m,J=9.6Hz,3H).
Embodiment 27
50ml single port bottles are taken, the B in the triethylamine of 7ml anhydrous methylene chlorides, 0.246g, and 0.1g following formulas is sequentially added1, It is stirred to dissolve, under ice bath, Deca is dissolved with 0.220gA7Dichloromethane solution, room temperature magnetic agitation 8h react.Reaction terminates Afterwards, washed three times with saturated common salt, anhydrous sodium sulfate drying organic faciess 1 hour.It is 5 that silicagel column petroleum ether is crossed than ethyl acetate:1 Separate, that is, obtain following formula: compound, yield 77%, purity 94%（HPLC）.Afterwards its biological activity is tested.
Net reaction is as follows:
Mass spectrometric data：MS m/z：269.01（M+1,100）.Nuclear magnetic data：1H NMR(501MHz,DMSO)δ10.11(s, 1H),8.08(dd,J=12.5Hz,2H),7.05-6.86(m,J=9.8Hz,2H)6.38(m,J=9.6Hz,1H).
Embodiment 28
50ml single port bottles are taken, the B in the triethylamine of 7ml anhydrous methylene chlorides, 0.223g, and 0.1g following formulas is sequentially added3, It is stirred to dissolve, under ice bath, Deca is dissolved with 0.200gA7Dichloromethane solution, room temperature magnetic agitation 8h react.Reaction terminates Afterwards, washed three times with saturated common salt, anhydrous sodium sulfate drying organic faciess 1 hour.It is 5 that silicagel column petroleum ether is crossed than ethyl acetate:1 Separate, that is, obtain following formula: compound, yield 85%, purity 97%（HPLC）.Afterwards its biological activity is tested.
Net reaction is as follows:
Mass spectrometric data：MS m/z：282.03（M+1,100）.Nuclear magnetic data：1H NMR(501MHz,DMSO)δ10.21(s, 1H),8.32(s,1H),8.08(d,J=13.6Hz,1H),7.07-6.86(m,J=17.8Hz,3H),3.85(s,3H),2.27 (s,3H).
Embodiment 29
50ml single port bottles are taken, the B in the triethylamine of 7ml anhydrous methylene chlorides, 0.112g, and 0.1g following formulas is sequentially added6, It is stirred to dissolve, under ice bath, Deca is dissolved with 0.034gA7Dichloromethane solution, room temperature magnetic agitation 8h react.Reaction terminates Afterwards, washed three times with saturated common salt, anhydrous sodium sulfate drying organic faciess 1 hour.It is 5 that silicagel column petroleum ether is crossed than ethyl acetate:1 Separate, that is, obtain following formula: compound, yield 93%, purity 97%（HPLC）.Afterwards its biological activity is tested.
Net reaction is as follows:
Mass spectrometric data：MS m/z：238.00（M+1,100）.Nuclear magnetic data：1H NMR(501MHz,DMSO)δ10.21(s, 1H),8.08(d,J=8.6Hz,1H),7.51-6.86(m,J=7.8Hz,6H).
Embodiment 30
50ml single port bottles are taken, the B in the triethylamine of 7ml anhydrous methylene chlorides, 0.244g, and 0.1g following formulas is sequentially added1, It is stirred to dissolve, under ice bath, Deca is dissolved with 0.275gA8Dichloromethane solution, room temperature magnetic agitation 8h react.Reaction terminates Afterwards, washed three times with saturated common salt, anhydrous sodium sulfate drying organic faciess 1 hour.It is 5 that silicagel column petroleum ether is crossed than ethyl acetate:1 Separate, that is, obtain following formula: compound, yield 74%, purity 94%（HPLC）.Afterwards its biological activity is tested.
Net reaction is as follows:
Mass spectrometric data：MS m/z：315.00（M+1,100）.Nuclear magnetic data：1H NMR(501MHz,DMSO)δ10.21(s, 1H),8.09(d,J=12.6Hz,1H),7.83(s,1H),7.49(s,1H),7.05-6.38(m,J=9.6Hz,2H),3.83(s, 3H).
Embodiment 31
50ml single port bottles are taken, the B in the triethylamine of 7ml anhydrous methylene chlorides, 0.221g, and 0.1g following formulas is sequentially added3, It is stirred to dissolve, under ice bath, Deca is dissolved with 0.249gA8Dichloromethane solution, room temperature magnetic agitation 8h react.Reaction terminates Afterwards, washed three times with saturated common salt, anhydrous sodium sulfate drying organic faciess 1 hour.It is 5 that silicagel column petroleum ether is crossed than ethyl acetate:1 Separate, that is, obtain following formula: compound, yield 96%, purity 95%（HPLC）.Afterwards its biological activity is tested.
Net reaction is as follows:
Mass spectrometric data：MS m/z：328.02（M+1,100）.Nuclear magnetic data：1H NMR(501MHz,DMSO)δ9.79(s, 1H),8.32(s,1H),7.83(s,1H),7.49(s,1H),7.07-6.95(m,J=8.1Hz,2H),3.83(s,3H),2.27 (s,
3H).
Embodiment 32
50ml single port bottles are taken, the B in the triethylamine of 7ml anhydrous methylene chlorides, 0.271g, and 0.1g following formulas is sequentially added4, It is stirred to dissolve, under ice bath, Deca is dissolved with 0.304gA8Dichloromethane solution, room temperature magnetic agitation 8h react.Reaction terminates Afterwards, washed three times with saturated common salt, anhydrous sodium sulfate drying organic faciess 1 hour.It is 5 that silicagel column petroleum ether is crossed than ethyl acetate:1 Separate, that is, obtain following formula: compound, yield 78%, purity 94%（HPLC）.Afterwards its biological activity is tested.
Net reaction is as follows:
Mass spectrometric data：MS m/z：302.98（M+1,100）.Nuclear magnetic data：1H NMR(501MHz,DMSO)δ10.37(s, 1H),8.49(s,1H),7.95(s,1H),7.83(s,1H),7.49(s,1H),7.34(m,J=9.8Hz,2H).
Embodiment 33
50ml single port bottles are taken, the B in the triethylamine of 7ml anhydrous methylene chlorides, 0.188g, and 0.1g following formulas is sequentially added5, It is stirred to dissolve, under ice bath, Deca is dissolved with 0.211gA8Dichloromethane solution, room temperature magnetic agitation 8h react.Reaction terminates Afterwards, washed three times with saturated common salt, anhydrous sodium sulfate drying organic faciess 1 hour.It is 5 that silicagel column petroleum ether is crossed than ethyl acetate:1 Separate, that is, obtain following formula: compound, yield 89%, purity 94%（HPLC）.Afterwards its biological activity is tested.
Net reaction is as follows:
Mass spectrometric data：MS m/z：351.98（M+1,100）.Nuclear magnetic data：1H NMR(501MHz,DMSO)δ10.56(s, 1H),7.83(s,1H),7.58(dd,J=8.7Hz,2H),7.49(s,1H),7.46(dd,J=10.6Hz,2H),.
Cell bio-activity test experiments
Experimental principle：Compound anticancer growth detail can be with measuring through MTT methods.The original of mtt assay Reason is：Yellow Thiazolyl blue may pass through cell membrane and enter intracellular, and the succinate dehydrogenase in living cells mitochondria can allow external source Property MTT be reduced into the royal purple crystallization first a ceremonial jade-ladle, used in libation being deposited in cell, but dead cell is but without this function.Dimethyl sulfoxide is used again Dissolving first a ceremonial jade-ladle, used in libation.At 570nm wavelength, its light absorption value is determined with enzyme-linked immunosorbent assay instrument, to obtain indirectly living cells quantity.
Experiment material：HCT116（Human colon cancer cell）, Hela（Human cervical carcinoma cell）, (human liver cancer is thin for MHCC97L Born of the same parents).Cultivate with DMEM+10%FBS culture medium culturings or using 1640+10%FBS respectively.
Test method and interpretation of result：
Experimental group：The medicine of+10 μ l variable concentrations of 190 μ l cell suspension（Final concentration of 10-5-10-10）
Blank control group：200μl PBS
Negative control group：+ 10 μ l 2%DMSO of 190 μ l cell suspension（DMSO final concentration of 0.1%）
Positive controls：The compound of+10 μ l variable concentrations of 190 μ l cell suspension
A. cell is inoculated in 96 orifice plates, and inoculum concentration is 1500/hole, and 190 μ l/ holes are positioned over 37 DEG C, 5% CO2Culture Overnight incubation in case.
B. the medicine that next day adds 10 μ l different per hole, medicine final concentration of 10-5-10-10M, if three parallel holes, 37 DEG C, 5% CO2Incubator is incubated 72 hours.
C. the MTT, 37 DEG C 5% of CO of 20 μ l 5mg/ml are added per hole2Incubator is incubated 4 hours.
D. supernatant is abandoned, and the DMSO of 100 μ l, concussion is added per hole.
E.570nm reading, calculates cell survival rate, calculates GI50 according to result, obtains table 1 below
1 structural formula of compound of table and activity data are as follows（μM）

Claims (9)

1. there is the amides compound of anti-tumor activity, it is characterised in that：The structure of amides compound is as led to formula I institute Show；
Wherein：R1、R2Independently selected from aromatic radical or heterocyclic radical.
2. amides compound as claimed in claim 1, it is characterised in that aromatic radical is phenyl that is unsubstituted or replacing, Heterocyclic radical is any one in oxygen-containing heterocycle that is unsubstituted or replacing, sulfur heterocyclic ring base or nitrogen heterocycle.
3. amides compound as claimed in claim 2, it is characterised in that substituent group is taken for monosubstituted, two replacements or three Generation, one or more in halogen, nitro, methoxyl group, methyl or trifluoromethyl of substituent group independence.
4. amides compound as claimed in claim 2, it is characterised in that unsubstituted or replace oxygen-containing heterocycle, contain Thia ring group and or nitrogen heterocycle be five yuan or hexa-member heterocycle.
5. amides compound as claimed in claim 2, it is characterised in that heterocyclic radical is pyridine that is unsubstituted or replacing Base, furan ring group or thienyl, substituent group is monosubstituted, two replacements or three replacements, substituent group independence selected from halogen, nitre One or more in base, methoxyl group, methyl or trifluoromethyl.
6. the amides compound with anti-tumor activity as described in one of claim 1-5 is used as histone methyl SET7 Inhibitor, the application in preparation treatment, prevention, the antitumor drug for alleviating tumor.
7. application as claimed in claim 6, it is characterised in that the antitumor drug for treatment, prevention or alleviate breast carcinoma, Cervical cancer or the medicine of hepatocarcinoma.
8. application as claimed in claim 6, it is characterised in that the weight percent of the active component in described antitumor drug It is 25-80% than content.
9. application as claimed in claim 6, it is characterised in that described antitumor drug is tablet, capsule, powder, ball Agent, granule or Emulsion.
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