CN104130175A - Indolone derivatives having different positions substituted and application thereof - Google Patents

Indolone derivatives having different positions substituted and application thereof Download PDF

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Publication number
CN104130175A
CN104130175A CN201410264059.1A CN201410264059A CN104130175A CN 104130175 A CN104130175 A CN 104130175A CN 201410264059 A CN201410264059 A CN 201410264059A CN 104130175 A CN104130175 A CN 104130175A
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methoxy
phenyl
benzyl
indole
indole dione
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郁彭
韩开林
樊振川
滕玉鸥
周瑶
宋彬彬
曲昕
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Tianjin University of Science and Technology
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Tianjin University of Science and Technology
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04—Indoles; Hydrogenated indoles
    • C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
    • C07D209/32—Oxygen atoms
    • C07D209/38—Oxygen atoms in positions 2 and 3, e.g. isatin
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04—Indoles; Hydrogenated indoles
    • C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
    • C07D209/40—Nitrogen atoms, not forming part of a nitro radical, e.g. isatin semicarbazone
    • 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
    • C07D401/04—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 directly linked by a ring-member-to-ring-member bond
    • 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
    • C07D409/04—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 directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/10—Spiro-condensed systems
    • C07D491/113—Spiro-condensed systems with two or more oxygen atoms as ring hetero atoms in the oxygen-containing ring

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Indole Compounds (AREA)

Abstract

The invention relates to indolone derivatives having different positions substituted and an application thereof, and particularly relates to preparation of the indolone derivatives having the different positions substituted and the application of the indolone derivatives in preparation of anti-tumor drugs, wherein in the structural formula, R1 is one of benzyl or alkyl compounds, R2 is one of hydrogen or halogen or aryl compounds, R3 is one of hydrogen or halogen or aryl or five-membered heterocyclic or six-membered heterocyclic compounds, R4 is one of hydrogen or halogen or aryl compounds, and R5 is one of hydrogen or halogen or aryl compounds. The indolone derivatives having the different positions substituted are synthesized for the first time, anti-tumor activity tests of the synthesized compounds aiming at human hepatoma cells (HepG2), human leukemia cells (K562) and human colon cancer cells (HT-29) are performed, and results show that IC50 of the derivatives is less than 10 [mu]M.

Description

Different positions substituted indole ketones derivant and application thereof
Technical field
The invention belongs to new compound preparation method and Application Areas, especially a kind of different positions substituted indole ketones derivant and application thereof.
Background technology
The method for the treatment of cancer is chemotherapy at present, wherein a lot of medicines are the growths of synthesizing to come anticancer by suppressing DNA, these medicines not only have lethality to cancer cells, and normal cell is also had to same lethal effect, and these medicines have very large toxic side effect conventionally.Therefore, study new anticancer approach, searching is synthetic easy, and toxic side effect is little, and the cancer therapy drug that resistance is high has become the focus of current drug research.
Isatin has another name called 2; 3-istain; the antitumor effective constituent of traditional Chinese medicine indigo naturalis; it is 1 years old; 2; on 3 and phenyl ring, polytype chemical reaction can occur, for its derivative synthetic provides wide space, the organic synthesis that the isatin of therefore take is at present substrate or the synthetic and active research of isatin and derivative thereof are very active.
Summary of the invention
The object of the present invention is to provide a kind of preparation method and application thereof of different positions substituted indole ketones derivant, the application synthesizes different positions substituted indole ketones derivant first, this analog derivative has good anti-tumor activity, synthetic simple with purification process.
Object of the present invention is achieved through the following technical solutions:
A different positions substituted indole ketones derivant, the general structure of derivative is as follows:
Wherein R1 is a kind of of benzyl or alkylate, R2 is a kind of of hydrogen or halogen or aryl compound, R3 is hydrogen or halogen or aryl or five-membered ring or 6-membered heterocyclic compound, R4 is a kind of of hydrogen or halogen or aryl compound, R5 is a kind of of hydrogen or halogen or aryl compound, and R6 is HH or OH or OCH 2cH 2o or NOH or FF or OHCH 3or benzene benzylidene or 4-p-methoxy-phenyl benzylidene or 4 trifluoromethyl benzylidenes is a kind of.
Described R1 is hydrogen, methyl, ethyl, benzyl, 4-chlorobenzyl, 4-luorobenzyl, 4-methoxy-benzyl, 4-bromobenzyl, 4-cyano group benzyl, 3,4-dichloro benzyl, 3, one of 5-dimethyl benzyl, 2-benzene oxygen ethyl, 2-chlorobenzyl, 3-chlorobenzyl, 2-bromobenzyl, 3-bromobenzyl, 2-naphthalene benzyl.
Described R2 is one of hydrogen, methyl, methoxyl group, fluorine, chlorine, bromine, iodine, 4-p-methoxy-phenyl.
Described R3 is hydrogen, methyl, methoxyl group, fluorine, chlorine, bromine, iodine, phenyl, 4-p-methoxy-phenyl, 4-Trifluoromethoxyphen-l, 4-aminomethyl phenyl, 4-cyano-phenyl, 4-trifluoromethyl, 4-hydroxy phenyl, 4-tert-butyl-phenyl, 4-fluorophenyl, 4-methyl-formiate phenyl, 3,4-Dimethoxyphenyl, 3, one of 5-Dimethoxyphenyl, 4-ethoxyl phenenyl, 2-p-methoxy-phenyl, 3-p-methoxy-phenyl, 3-thiophene, 4-pyridine.
Described R4 is one of hydrogen, methyl, methoxyl group, fluorine, chlorine, bromine, iodine, 4-p-methoxy-phenyl.
Described R5 is one of hydrogen, methyl, methoxyl group, fluorine, chlorine, bromine, iodine, 4-p-methoxy-phenyl.
Described R6 is HH, OH, OCH 2cH 2o, NOH, FF, OHCH 3, one of benzene benzylidene, 4-p-methoxy-phenyl benzylidene, 4 trifluoromethyl benzylidenes
Described derivative is 1-methyl-5-(4-p-methoxy-phenyl) indole dione, or 1-ethyl-5-(4-p-methoxy-phenyl) indole dione, or 1-benzyl-5-(4-p-methoxy-phenyl) indole dione, or 1-(4-chlorobenzyl)-5-(4-p-methoxy-phenyl) indole dione, or 1-(2-chlorobenzyl)-5-(4-p-methoxy-phenyl) indole dione, or 1-(3-chlorobenzyl)-5-(4-p-methoxy-phenyl) indole dione, or 1-(4-luorobenzyl)-5-(4-p-methoxy-phenyl) indole dione, or 1-(4-bromobenzyl)-5-(4-p-methoxy-phenyl) indole dione, or 1-(2-bromobenzyl)-5-(4-p-methoxy-phenyl) indole dione, or 1-(3-bromobenzyl)-5-(4-p-methoxy-phenyl) indole dione, or 1-(4-methyl-benzyl)-5-(4-p-methoxy-phenyl) indole dione, or 1-(4-methoxy-benzyl)-5-(4-p-methoxy-phenyl) indole dione, or 1-(4-cyano group benzyl)-5-(4-p-methoxy-phenyl) indole dione, or 1-(4-trifluoromethyl benzyl)-5-(4-p-methoxy-phenyl) indole dione, or 1-(3, 4-dichloro benzyl)-5-(4-p-methoxy-phenyl) indole dione, or 1-(3, 5-dimethyl benzyl)-5-(4-p-methoxy-phenyl) indole dione, or 1-(2-naphthalene benzyl)-5-(4-p-methoxy-phenyl) indole dione, or 1-(2-benzene oxygen ethyl)-5-(4-p-methoxy-phenyl) indole dione, or 1-(4-bromobenzyl)-5-(4-aminomethyl phenyl) indole dione, or 1-(4-bromobenzyl)-5-Phenylindole diketone, or 1-(4-bromobenzyl)-5-(4-cyano-phenyl) indole dione, or 1-(4-bromobenzyl)-5-(4-trifluoromethyl) indole dione, or 1-(4-bromobenzyl)-5-(4-tert-butyl-phenyl) indole dione, or 1-(4-methoxy-benzyl)-5-(4-Trifluoromethoxyphen-l) indole dione, or 1-(4-methoxy-benzyl)-5-(4-aminomethyl phenyl) indole dione, or 1-(4-methoxy-benzyl)-5-Phenylindole diketone, or 1-(4-methoxy-benzyl)-5-(4-cyano-phenyl) indole dione, or 1-(4-methoxy-benzyl)-5-(4-trifluoromethyl) indole dione, or 1-(4-methoxy-benzyl)-5-(4-tert-butyl-phenyl) indole dione, or 1-(4-methoxy-benzyl)-5-(4-hydroxy phenyl) indole dione, or 1-(4-methoxy-benzyl)-5-(4-ethoxyl phenenyl) indole dione, or 1-(4-methoxy-benzyl)-5-(4-fluorophenyl) indole dione, or 1-(4-methoxy-benzyl)-5-(2-p-methoxy-phenyl) indole dione, or 1-(4-methoxy-benzyl)-5-(3-p-methoxy-phenyl) indole dione, or 1-(4-methoxy-benzyl)-5-(3, 4-Dimethoxyphenyl) indole dione, or 1-(4-methoxy-benzyl)-5-Phenylindole diketone, or 1-(4-methoxy-benzyl)-5-(3, 5-Dimethoxyphenyl) indole dione, or 1-(4-methoxy-benzyl)-5-(3-thiophene) indole dione, or 1-(4-methoxy-benzyl)-5-(4-pyridine) indole dione, or 1-(4-methoxy-benzyl)-5-(4-methyl-formiate phenyl) indole dione, or 1-(4-methoxy-benzyl)-4-(4-p-methoxy-phenyl) indole dione, or 1-(4-methoxy-benzyl)-6-(4-p-methoxy-phenyl) indole dione, or 1-(4-methoxy-benzyl)-7-(4-p-methoxy-phenyl) indole dione, or 1-(4-methoxy-benzyl)-5-(4-p-methoxy-phenyl)-3-oximido indolone, or 1-(4-methoxy-benzyl)-5-(4-p-methoxy-phenyl)-3-hydroxyindole ketone, or 1-(4-methoxy-benzyl)-5-(4-p-methoxy-phenyl)-3, 3-contracting dialdehyde indolone, or 1-(4-methoxy-benzyl)-5-(4-p-methoxy-phenyl)-2-indolinone, or 1-(4-methoxy-benzyl)-5-(4-p-methoxy-phenyl)-(3, 3-hydroxymethyl) indolone, or 1-(4-methoxy-benzyl)-5-(4-p-methoxy-phenyl)-(3, 3-difluoro) indolone, or 1-(4-methoxy-benzyl)-5-(4-p-methoxy-phenyl)-3-benzylidene Phenylindole ketone, or 1-(4-methoxy-benzyl)-5-(4-p-methoxy-phenyl)-3-(4-p-methoxy-phenyl benzylidene) indolone, or 1-(4-methoxy-benzyl)-5-(4-p-methoxy-phenyl)-3-(4-trifluoromethyl benzylidene) indolone.
A preparation method for different positions substituted indole ketones derivant, route is as follows:
Wherein, R1 is a kind of of benzyl or alkylate, R2 is a kind of of hydrogen or halogen or aryl compound, R3 is hydrogen or halogen or aryl or five-membered ring or 6-membered heterocyclic compound, R4 is a kind of of hydrogen or halogen or aryl compound, R5 is a kind of of hydrogen or halogen or aryl compound, and R6 is HH or OH or OCH 2cH 2o or NOH or FF or OHCH 3or benzene benzylidene or 4-p-methoxy-phenyl benzylidene or 4 trifluoromethyl benzylidenes is a kind of.
And, it is characterized in that: described R1 is hydrogen, methyl, ethyl, benzyl, 4-chlorobenzyl, 4-luorobenzyl, 4-methoxy-benzyl, 4-bromobenzyl, 4-cyano group benzyl, 3,4-dichloro benzyl, 3, one of 5-dimethyl benzyl, 2-benzene oxygen ethyl, 2-chlorobenzyl, 3-chlorobenzyl, 2-bromobenzyl, 3-bromobenzyl, 2-naphthalene benzyl.Described R2 is one of hydrogen, methyl, methoxyl group, fluorine, chlorine, bromine, iodine, 4-p-methoxy-phenyl.Described R3 is hydrogen, methyl, methoxyl group, fluorine, chlorine, bromine, iodine, phenyl, 4-p-methoxy-phenyl, 4-Trifluoromethoxyphen-l, 4-aminomethyl phenyl, 4-cyano-phenyl, 4-trifluoromethyl, 4-hydroxy phenyl, 4-tert-butyl-phenyl, 4-fluorophenyl, 4-methyl-formiate phenyl, 3,4-Dimethoxyphenyl, 3, one of 5-Dimethoxyphenyl, 4-ethoxyl phenenyl, 2-p-methoxy-phenyl, 3-p-methoxy-phenyl, 3-thiophene, 4-pyridine.Described R4 is one of hydrogen, methyl, methoxyl group, fluorine, chlorine, bromine, iodine, 4-p-methoxy-phenyl.Described R5 is one of hydrogen, methyl, methoxyl group, fluorine, chlorine, bromine, iodine, 4-p-methoxy-phenyl.Described R6 is HH, OH, OCH 2cH 2o, NOH, FF, OHCH 3, one of benzene benzylidene, 4-p-methoxy-phenyl benzylidene, 4-trifluoromethyl benzylidene.
The preparation of different positions substituted indole ketones derivant and the application in preparing antitumor drug thereof,, the research of described compound to human liver cancer cell (HepG2), human leukemia cell (K562), human colon cancer cell (HT-29) anti-tumor activity.Described compound is as the antitumor drug of preparation treatment people liver cancer, human leukemia, human colon carcinoma.
Advantage of the present invention and positively effect:
The application synthesizes different positions substituted indole ketone derivatives, and this analog derivative has good biological activity, its IC for human liver cancer cell (HepG2), human leukemia cell (K562), human colon cancer cell (HT-29) 50<10 μ M.The present invention has opened up the research direction of a class new type antineoplastic medicine.
Accompanying drawing explanation
Fig. 1 is the proton nmr spectra of 1-methyl-5-(4-p-methoxy-phenyl) indole dione; Fig. 2 is the proton nmr spectra of 1-ethyl-5-(4-p-methoxy-phenyl) indole dione; Fig. 3 is the proton nmr spectra of 1-(4-bromobenzyl)-5-(4-aminomethyl phenyl) indole dione; Fig. 4 is the proton nmr spectra of 1-(4-methoxy-benzyl)-5-(4-Trifluoromethoxyphen-l) indole dione; Fig. 5 is the proton nmr spectra of 1-(4-methoxy-benzyl)-5-(4-aminomethyl phenyl) indole dione; Fig. 6 is the proton nmr spectra of 1-(4-methoxy-benzyl)-4-(4-p-methoxy-phenyl) indole dione; Fig. 7 is the proton nmr spectra of 1-(4-methoxy-benzyl)-6-(4-p-methoxy-phenyl) indole dione; Fig. 8 is the proton nmr spectra of 1-(4-methoxy-benzyl)-7-(4-p-methoxy-phenyl) indole dione; Fig. 9 is the proton nmr spectra of 1-(4-methoxy-benzyl)-5-(4-p-methoxy-phenyl)-3-oximido indolone; Figure 10 is the proton nmr spectra of 1-(4-methoxy-benzyl)-5-(4-p-methoxy-phenyl)-3-hydroxyindole ketone; Figure 11 is 1-(4-methoxy-benzyl)-5-(4-p-methoxy-phenyl)-3, the proton nmr spectra of 3-contracting dialdehyde indolone; Figure 12 is the proton nmr spectra of 1-(4-methoxy-benzyl)-5-(4-p-methoxy-phenyl)-2-indolinone; Figure 13 is the proton nmr spectra of 1-(4-methoxy-benzyl)-5-(4-p-methoxy-phenyl)-(3,3-hydroxymethyl) indolone; Figure 14 is the proton nmr spectra of 1-(4-methoxy-benzyl)-5-(4-p-methoxy-phenyl)-(3,3-difluoro) indolone; Figure 15 is the proton nmr spectra of 1-(4-methoxy-benzyl)-5-(4-p-methoxy-phenyl)-3-benzylidene Phenylindole ketone.
Embodiment
In order to understand the present invention, below in conjunction with embodiment, the invention will be further described; Following embodiment is illustrative, is not determinate, can not limit protection scope of the present invention with following embodiment.
Formula I compound antitumor drug of the present invention, the present invention's design be take indole dione as female ring, main passing through 1, the modification of 5 improves its biological activity, on 5, introduce length that halogen, alkyl, aromatic ring, five-membered ring, hexa-member heterocycle study space size, electronic effect and chain to active impact, on 1, introduce the influence factor that alkyl and the different benzyls that replace are studied N-1 position group; Then, more above-mentioned modification is carried out in Isosorbide-5-Nitrae position, 1,6,1,7, study the impact of different positions on anti-tumor activity.Different positions substituted indole ketone derivatives of the present invention can be used in combination with other antitumor activity composition.Formula I compound of the present invention is preferably as antitumor drug.
The present invention is based on indolone has good biological activity, synthesizes first different positions substituted indole ketone derivatives, and this analog derivative has good anti-tumor activity, its majority of compounds IC 50<10 μ M.
Compound involved in the present invention application in medicine for treating tumor thing, includes but not limited to the application in treatment people liver cancer, human leukemia, human colon carcinoma medicine.
The invention provides formula I compound
Wherein R1 is a kind of of benzyl or alkylate; R2 is a kind of of hydrogen or halogen or aryl compound; R3 is hydrogen or halogen or aryl or five-membered ring or 6-membered heterocyclic compound; R4 is a kind of of hydrogen or halogen or aryl compound; R5 is a kind of of hydrogen or halogen or aryl compound, and R6 is HH or OH or OCH 2cH 2o or NOH or FF or OHCH 3or benzene benzylidene or 4-p-methoxy-phenyl benzylidene or 4-trifluoromethyl benzylidene is a kind of.
R1 is preferably hydrogen, methyl, ethyl, benzyl, 4-chlorobenzyl, 4-luorobenzyl, 4-methoxy-benzyl, 4-bromobenzyl, 4-cyano group benzyl, 3,4-dichloro benzyl, 3,5-dimethyl benzyl, 2-benzene oxygen ethyl, 2-chlorobenzyl, 3-chlorobenzyl, 2-bromobenzyl, 3-bromobenzyl, 2-naphthalene benzyl.
R2 is preferably hydrogen, methyl, methoxyl group, fluorine, chlorine, bromine, iodine, 4-p-methoxy-phenyl.
R3 is preferably hydrogen, methyl, methoxyl group, fluorine, chlorine, bromine, iodine, phenyl, 4-p-methoxy-phenyl, 4-Trifluoromethoxyphen-l, 4-aminomethyl phenyl, 4-cyano-phenyl, 4-trifluoromethyl, 4-hydroxy phenyl, 4-tert-butyl-phenyl, 4-fluorophenyl, 4-methyl-formiate phenyl, 3,4-Dimethoxyphenyl, 3,5-Dimethoxyphenyl, 4-ethoxyl phenenyl, 2-p-methoxy-phenyl, 3-p-methoxy-phenyl, 3-thiophene, 4-pyridine.
R4 is preferably hydrogen, methyl, methoxyl group, fluorine, chlorine, bromine, iodine, 4-p-methoxy-phenyl.
R5 is preferably hydrogen, methyl, methoxyl group, fluorine, chlorine, bromine, iodine, 4-p-methoxy-phenyl.
R6 is preferably HH, OH, OCH 2cH 2o, NOH, FF, OHCH 3, benzene benzylidene, 4-p-methoxy-phenyl benzylidene, 4-trifluoromethyl benzylidene.
The present invention is particularly including compound:
(1) 1-methyl-5-(4-p-methoxy-phenyl) indole dione
(2) 1-ethyl-5-(4-p-methoxy-phenyl) indole dione;
(3) 1-benzyl-5-(4-p-methoxy-phenyl) indole dione;
(4) 1-(4-chlorobenzyl)-5-(4-p-methoxy-phenyl) indole dione;
(5) 1-(2-chlorobenzyl)-5-(4-p-methoxy-phenyl) indole dione;
(6) 1-(3-chlorobenzyl)-5-(4-p-methoxy-phenyl) indole dione;
(7) 1-(4-luorobenzyl)-5-(4-p-methoxy-phenyl) indole dione;
(8) 1-(4-bromobenzyl)-5-(4-p-methoxy-phenyl) indole dione;
(9) 1-(2-bromobenzyl)-5-(4-p-methoxy-phenyl) indole dione;
(10) 1-(3-bromobenzyl)-5-(4-p-methoxy-phenyl) indole dione;
(11) 1-(4-methyl-benzyl)-5-(4-p-methoxy-phenyl) indole dione;
(12) 1-(4-methoxy-benzyl)-5-(4-p-methoxy-phenyl) indole dione;
(13) 1-(4-cyano group benzyl)-5-(4-p-methoxy-phenyl) indole dione;
(14) 1-(4-trifluoromethyl benzyl)-5-(4-p-methoxy-phenyl) indole dione;
(15) 1-(3,4-dichloro benzyl)-5-(4-p-methoxy-phenyl) indole dione;
(16) 1-(3,5-dimethyl benzyl)-5-(4-p-methoxy-phenyl) indole dione;
(17) 1-(2-naphthalene benzyl)-5-(4-p-methoxy-phenyl) indole dione;
(18) 1-(2-benzene oxygen ethyl)-5-(4-p-methoxy-phenyl) indole dione;
(19) 1-(4-bromobenzyl)-5-(4-aminomethyl phenyl) indole dione;
(20) 1-(4-bromobenzyl)-5-Phenylindole diketone;
(21) 1-(4-bromobenzyl)-5-(4-cyano-phenyl) indole dione;
(22) 1-(4-bromobenzyl)-5-(4-trifluoromethyl) indole dione;
(23) 1-(4-bromobenzyl)-5-(4-tert-butyl-phenyl) indole dione;
(24) 1-(4-methoxy-benzyl)-5-(4-Trifluoromethoxyphen-l) indole dione;
(25) 1-(4-methoxy-benzyl)-5-(4-aminomethyl phenyl) indole dione;
(26) 1-(4-methoxy-benzyl)-5-Phenylindole diketone;
(27) 1-(4-methoxy-benzyl)-5-(4-cyano-phenyl) indole dione;
(28) 1-(4-methoxy-benzyl)-5-(4-trifluoromethyl) indole dione;
(29) 1-(4-methoxy-benzyl)-5-(4-tert-butyl-phenyl) indole dione;
(30) 1-(4-methoxy-benzyl)-5-(4-hydroxy phenyl) indole dione;
(31) 1-(4-methoxy-benzyl)-5-(4-ethoxyl phenenyl) indole dione;
(32) 1-(4-methoxy-benzyl)-5-(4-fluorophenyl) indole dione;
(33) 1-(4-methoxy-benzyl)-5-(2-p-methoxy-phenyl) indole dione;
(34) 1-(4-methoxy-benzyl)-5-(3-p-methoxy-phenyl) indole dione;
(35) 1-(4-methoxy-benzyl)-5-(3,4-Dimethoxyphenyl) indole dione;
(36) 1-(4-methoxy-benzyl)-5-(3,5-Dimethoxyphenyl) indole dione;
(37) 1-(4-methoxy-benzyl)-5-(3-thiophene) indole dione;
(38) 1-(4-methoxy-benzyl)-5-(4-pyridine) indole dione;
(39) 1-(4-methoxy-benzyl)-5-(4-methyl-formiate phenyl) indole dione;
(40) 1-(4-methoxy-benzyl)-4-(4-p-methoxy-phenyl) indole dione;
(41) 1-(4-methoxy-benzyl)-6-(4-p-methoxy-phenyl) indole dione;
(42) 1-(4-methoxy-benzyl)-7-(4-p-methoxy-phenyl) indole dione;
(43) 1-(4-methoxy-benzyl)-5-(4-p-methoxy-phenyl)-3-oximido indolone;
(44) 1-(4-methoxy-benzyl)-5-(4-p-methoxy-phenyl)-3-hydroxyindole ketone;
(45) 1-(4-methoxy-benzyl)-5-(4-p-methoxy-phenyl)-3,3-contracting dialdehyde indolone;
(46) 1-(4-methoxy-benzyl)-5-(4-p-methoxy-phenyl)-2-indolinone;
(47) 1-(4-methoxy-benzyl)-5-(4-p-methoxy-phenyl)-(3,3-hydroxymethyl) indolone;
(48) 1-(4-methoxy-benzyl)-5-(4-p-methoxy-phenyl)-(3,3-difluoro) indolone;
(49) 1-(4-methoxy-benzyl)-5-(4-p-methoxy-phenyl)-3-benzylidene Phenylindole ketone;
(50) 1-(4-methoxy-benzyl)-5-(4-p-methoxy-phenyl)-3-(4-p-methoxy-phenyl benzylidene) indolone;
(51) 1-(4-methoxy-benzyl)-5-(4-p-methoxy-phenyl)-3-(4-trifluoromethyl benzylidene) indolone;
The synthetic route of formula I
R1 is preferably hydrogen, methyl, ethyl, benzyl, 4-chlorobenzyl, 4-luorobenzyl, 4-methoxy-benzyl, 4-bromobenzyl, 4-cyano group benzyl, 3,4-dichloro benzyl, 3,5-dimethyl benzyl, 2-benzene oxygen ethyl, 2-chlorobenzyl, 3-chlorobenzyl, 2-bromobenzyl, 3-bromobenzyl, 2-naphthalene benzyl.
R2 is preferably hydrogen, methyl, methoxyl group, fluorine, chlorine, bromine, iodine, 4-p-methoxy-phenyl.
R3 is preferably hydrogen, methyl, methoxyl group, fluorine, chlorine, bromine, iodine, phenyl, 4-p-methoxy-phenyl, 4-Trifluoromethoxyphen-l, 4-aminomethyl phenyl, 4-cyano-phenyl, 4-trifluoromethyl, 4-hydroxy phenyl, 4-tert-butyl-phenyl, 4-fluorophenyl, 4-methyl-formiate phenyl, 3,4-Dimethoxyphenyl, 3,5-Dimethoxyphenyl, 4-ethoxyl phenenyl, 2-p-methoxy-phenyl, 3-p-methoxy-phenyl, 3-thiophene, 4-pyridine.
R4 is preferably hydrogen, methyl, methoxyl group, fluorine, chlorine, bromine, iodine, 4-p-methoxy-phenyl.
R5 is preferably hydrogen, methyl, methoxyl group, fluorine, chlorine, bromine, iodine, 4-p-methoxy-phenyl.
R6 is preferably HH, OH, OCH 2cH 2o, NOH, FF, OHCH 3, benzene benzylidene, 4-p-methoxy-phenyl benzylidene, 4-trifluoromethyl benzylidene.
Below describe the preparation experiment situation of above-mentioned 51 chemical combination in detail.
Illustrate 1
1-methyl-5-(4-p-methoxy-phenyl) indole dione
Get 5-bromo indole diketone 5.0g (0.022mol), 4-methoxyphenylboronic acid 4.0g (0.027mol), triphenyl phosphorus 7.0g (0.027mol), palladium 0.25g (0.0011mol), anhydrous acetic acid potassium 4.2g (0.031mol), join in microwave reaction bottle, in microwave reaction bottle, add 20mLN, dinethylformamide.Applying argon gas protection, 120 ℃ of reaction 30min in microwave reactor.After TLC detection reaction is complete, add a small amount of water, use dichloromethane extraction three times, merge organic phase, saturated common salt washing three times for organic phase, organic phase anhydrous sodium sulfate drying, desolventizing, sherwood oil are revolved in decompression: ethyl acetate=5:1200-300 order silicagel column purifying.Obtain 5-(4-p-methoxy-phenyl) indole dione, productive rate 55%.
Getting 5-(4-p-methoxy-phenyl) indole dione 0.2g (0.0008mol) joins in 25mL round-bottomed flask, in round-bottomed flask, add 2mLN, dinethylformamide, stirring is fully dissolved it, then adds Anhydrous potassium carbonate 0.33g (0.0024mol), then, slowly drip methyl iodide 0.17g (0.0012mol), under room temperature, react 6h, TLC detects raw material and disappears, stopped reaction.Add 15mL water, use dichloromethane extraction 3 times, merge organic phase, organic phase saturated common salt water washing, anhydrous sodium sulfate drying, with sherwood oil: ethyl acetate=8:1,200-300 order purification by silica gel column chromatography.Obtain 1-methyl-5-(4-p-methoxy-phenyl) indole dione 0.15g81%.
1H-NMR(400MHz,CDCl 3)δ:3.28(3H,s),3.85(3H,s),6.93-6.95(1H,d),6.97-6.99(2H,d),7.45-7.47(2H,m),7.77-7.79(2H,d).
13C-NMR(100MHz,CDCl 3):26.33,55.40,110.23,114.50,114.50,117.87,123.26,127.64,127.64,131.43,136.28,137.09,149.96,158.38,159.59,183.55.
Illustrate 2
1-ethyl-5-(4-p-methoxy-phenyl) indole dione
Getting 5-(4-p-methoxy-phenyl) indole dione 0.2g (0.0008mol) joins in 25mL round-bottomed flask, in round-bottomed flask, add 2mLN, dinethylformamide, stirring is fully dissolved it, then adds Anhydrous potassium carbonate 0.33g (0.0024mol), then, slowly add iodoethane 0.19g (0.0012mol), under room temperature, react 6h, TLC detects raw material and disappears, stopped reaction.Add 15mL water, use dichloromethane extraction 3 times, merge organic phase, organic phase saturated common salt water washing, anhydrous sodium sulfate drying, with sherwood oil: ethyl acetate=8:1,200-300 order purification by silica gel column chromatography.Obtain 1-ethyl-5-(4-p-methoxy-phenyl) indole dione, productive rate 64%.
1H-NMR(400MHz,CDCl 3)δ:1.32-1.35(3H,t),3.78-3.84(2H,m),3.85(3H,s),6.94-6.98(3H,t),7.43-7.46(2H,d),7.74-7.77(2H,t).
13C-NMR(100MHz,CDCl 3):12.60,35.08,55.40,110.33,114.50,114.50,118.06,123.47,127.63,127.63,131.47,136.24,136.90,149.16,158.00,159.57,183.91.
Illustrate 3
1-benzyl-5-(4-p-methoxy-phenyl) indole dione
Method is with specification sheets 2, productive rate 70%.
1HNMR(400MHz,CDCl 3)δ3.83(s,3H),4.95(s,2H),6.80-6.82(d,1H,J＝8.4Hz),6.94-6.96(d,2H,J＝8.4Hz),7.29-7.36(m,5H),7.39-7.41(d,2H,J＝8.4Hz),7.63-7.65(d,1H,J＝8.0Hz),7.78(s,1H).
13C-NMR(100MHz,CDCl 3):44.16,55.38,111.30,114.50,114.50,118.12,123.38,127.47,127.47,127.63,127.63,128.20,129.08,129.08,131.42,134.57,136.23,137.14,149.22,158.41,159.60,183.44.
Illustrate 4
1-(4-chlorobenzyl)-5-(4-p-methoxy-phenyl) indole dione
Method is with specification sheets 2, productive rate 79%.
1H-NMR(400MHz,CDCl 3)δ:3.84(3H,s),4.92(2H,s),6.77-6.79(1H,d),6.95-6.97(2H,d),7.28-7.35(4H,m),7.39-7.42(2H,d),7.65-7.67(1H,m),7.79(1H,d).
13C-NMR(100MHz,CDCl 3):43.52,55.39,111.11,114.52,114.52,118.13,123.52,127.65,127.65,128.87,128.87,129.30,129.30,131.31,133.10,134.16,136.26,137.35,148.86,158.37,159.64,183.18.
Illustrate 5
1-(2-chlorobenzyl)-5-(4-p-methoxy-phenyl) indole dione
Method is with specification sheets 2, productive rate 80%.
1H-NMR(400MHz,CDCl 3)δ:3.84(3H,s),5.08(2H,s),6.80-6.82(1H,d),6.95-6.97(2H,d),7.23-7.26(3H,m),7.41-7.45(3H,m),7.65-7.68(1H,m),7.81-7.82(1H,d).
13C-NMR(100MHz,CDCl 3):43.55,55.39,111.10,114.51,114.51,118.13,123.56,127.61,127.61,128.73,128.73,129.10,129.10,131.24,133.82,134.23,136.41,137.52,148.80,158.37,159.64,183.12
Illustrate 6
1-(3-chlorobenzyl)-5-(4-p-methoxy-phenyl) indole dione
Method is with specification sheets 2, productive rate 76%.
1H-NMR(400MHz,CDCl 3)δ:3.84(3H,s),4.93(2H,s),6.79-6.81(1H,d),6.95-6.97(2H,d),7.24-7.34(4H,m),7.41-7.43(2H,t),7.66-7.69(1H,m),7.81(1H,d).
13C-NMR(100MHz,CDCl 3):43.61,55.39,111.09,114.52,114.52,118.13,123.58,125.56,127.53,127.67,127.67,128.51,130.42,131.32,135.04,136.34,136.64,137.41,148.83,158.37,159.64,183.11.
Illustrate 7
1-(4-luorobenzyl)-5-(4-p-methoxy-phenyl) indole dione
Method is with specification sheets 2, productive rate 77%.
1H-NMR(400MHz,CDCl 3)δ:3.83(3H,s),4.92(2H,s),6.80-6.82(1H,d),6.94-6.96(2H,d),7.02-7.07(2H,t),7.32-7.36(2H,m),7.39-7.41(2H,d),7.65-7.67(1H,m),7.78(1H,d).
13C-NMR(100MHz,CDCl 3):43.47,55.39,111.12,114.51,114.51,115.96,116.17,118.13,123.49,127.64,127.64,129.26,129.35,130.38,130.42,131.33,136.24,137.29,148.95,158.36,159.63,183.28.
Illustrate 8
1-(4-bromobenzyl)-5-(4-p-methoxy-phenyl) indole dione
Method is with specification sheets 2, productive rate 82%.
1H-NMR(400MHz,CDCl 3)δ:3.84(3H,s),4.90(2H,s),6.77-6.79(1H,d),6.95-6.97(2H,d),7.23-7.25(2H,d),7.40-7.42(2H,d),7.48-7.50(2H,d),7.65-7.67(1H,m),7.79-7.80(1H,d).
13C-NMR(100MHz,CDCl 3):43.58,55.39,111.10,114.52,114.52,118.14,122.24,123.55,127.66,127.66,129.17,129.17,131.32,132.26,132.26,133.61,136.27,137.39,148.84,158.36,159.65,183.15.
Illustrate 9
1-(2-bromobenzyl)-5-(4-p-methoxy-phenyl) indole dione
Method is with specification sheets 2, productive rate 76%.
1H-NMR(400MHz,CDCl 3)δ:3.84(3H,s),5.06(2H,s),6.77-6.79(1H,d),6.95-6.97(2H,t),7.16-7.29(3H,m),7.41-7.43(2H,t),7.61-7.68(2H,m),7.81-7.82(1H,d).
13C-NMR(100MHz,CDCl 3):44.14,55.39,111.45,114.52,114.52,118.13,122.87,123.43,127.65,127.65,128.09,128.09,129.63,131.33,133.27,133.36,136.45,137.38,148.95,158.55,159.64,183.16.
Illustrate 10
1-(3-bromobenzyl)-5-(4-p-methoxy-phenyl) indole dione
Method is with specification sheets 2, productive rate 73%.
1H-NMR(400MHz,CDCl 3)δ:3.84(3H,s),4.91(2H,s),6.78-6.80(1H,m),6.95-6.97(2H,m),7.21-7.29(2H,m),7.40-7.50(4H,m),7.66-7.68(1H,m),7.80(1H,s).
13C-NMR(100MHz,CDCl 3):43.55,55.39,111.07,114.53,114.53,118.15,123.17,123.58,126.03,127.67,127.67,130.44,130.67,131.33,131.46,136.33,136.91,137.42,148.82,158.36,159.65,183.09.
Illustrate 11
1-(4-methyl-benzyl)-5-(4-p-methoxy-phenyl) indole dione
Method is with specification sheets 2, productive rate 79%.
1H-NMR(400MHz,CDCl 3)δ:2.33(3H,s),3.84(3H,s),4.91(2H,s),6.81-6.83(1H,d),6.94-6.96(2H,d),7.15-7.17(2H,d),7.23-7.26(2H,d),7.39-7.41(2H,d),7.63-7.65(1H,m),7.77-7.78(1H,d).
13C-NMR(100MHz,CDCl 3):21.13,43.94,55.38,111.33,114.49,114.49,118.12,123.37,127.50,127.50,127.63,127.63,129.73,129.73,131.49,136.22,137.08,138.02,149.29,158.39,159.57,183.57.
Illustrate 12
1-(4-methoxy-benzyl)-5-(4-p-methoxy-phenyl) indole dione
Method is with specification sheets 2, productive rate 90%.
1H-NMR(400MHz,CDCl 3)δ:3.78(3H,s),3.83(3H,s),4.88(2H,s),6.83-6.85(1H,d),6.86-6.88(2H,d),6.93-6.96(2H,t),7.27-7.29(2H,d),7.38-7.40(2H,d),7.63-7.65(1H,m),7.75-7.76(1H,d).
13C-NMR(100MHz,CDCl 3):43.64,55.30,55.38,111.32,114.45,114.45,114.49,114.49,118.12,123.32,126.55,127.61,127.61,128.96,128.96,131.43,136.18,137.04,149.26,158.37,159.50,159.58,183.59.
Illustrate 13
1-(4-cyano group benzyl)-5-(4-p-methoxy-phenyl) indole dione
Method is with specification sheets 2, productive rate 52%.
1H-NMR(400MHz,CDCl 3)δ:3.84(3H,s),5.01(2H,s),6.73-6.75(1H,d),6.96-6.98(2H,m),7.40-7.43(2H,m),7.46-7.48(2H,d),7.66-7.69(3H,m),7.82-7.83(1H,d).
13C-NMR(100MHz,CDCl 3):43.73,55.40,110.84,112.36,114.56,114.56,118.16,118.25,123.73,127.67,127.67,128.06,128.06,131.16,132.92,132.92,136.35,137.68,139.98,148.49,158.37,159.73,182.76.
Illustrate 14
1-(4-trifluoromethyl benzyl)-5-(4-p-methoxy-phenyl) indole dione
Method is with specification sheets 2, productive rate 75%.
1H-NMR(400MHz,CDCl 3)δ:7.624-7.600(2H,t),7.411-7.391(2H,m),7.366-7.350(1H,m),6.979-6.959(1H,d),4.632-4.623(2H,t),4.389-4.377(2H,m),3.940-3.927(2H,d),3.851-3.838(2H,d).
13CNMR(100MHz,CDCl 3)δ43.68,55.40,110.84,112.36,114.56,114.56,118.16,118.25,123.73,127.67,127.67,128.06,128.06,131.16,132.92,132.92,136.35,137.68,139.98,148.49,158.37,159.73,182.76.
Illustrate 15
1-(3,4-dichloro benzyl)-5-(4-p-methoxy-phenyl) indole dione
Method is with specification sheets 2, productive rate 62%.
1H-NMR(400MHz,CDCl 3)δ:3.84(3H,s),4.90(2H,s),6.77-6.79(1H,d),6.96-6.98(2H,d),7.19-7.21(1H,d),7.41-7.45(4H,m),7.68-7.70(1H,m),7.81-7.82(1H,d).
13C-NMR(100MHz,CDCl 3):43.11,55.39,110.89,114.56,114.56,118.19,123.68,126.74,127.67,127.67,129.40,131.12,131.27,132.58,133.35,134.86,136.32,137.60,148.57,158.33,159.72,182.85.
Illustrate 16
1-(3,5-dimethyl benzyl)-5-(4-p-methoxy-phenyl) indole dione
Method is with specification sheets 2, productive rate 83%.
1H-NMR(400MHz,CDCl 3)δ:2.29(6H,s),3.84(3H,s),4.86(2H,s),6.82-6.84(1H,d),6.93-6.96(5H,m),7.40-7.42(2H,m),7.64-7.66(1H,m),7.78(1H,d).
13CNMR(100MHz,CDCl 3)δ21.29,21.29,44.13,55.39,111.37,114.49,114.49,118.11,123.34,125.24,125.24,127.63,127.63,129.85,131.49,134.44,136.28,137.05,138.74,138.74,149.39,158.42,159.57,183.62.
13C-NMR:
Illustrate 17
1-(2-naphthalene benzyl)-5-(4-p-methoxy-phenyl) indole dione
Method is with specification sheets 2, productive rate 87%.
1H-NMR(400MHz,CDCl 3)δ:3.83(3H,s),5.12(2H,s),6.83-6.85(1H,d),6.93-6.95(2H,d),7.38-7.40(2H,d),7.43-7.46(1H,m),7.48-7.50(2H,m),7.59-7.62(1H,m),7.80-7.86(5H,m).
13C-NMR(100MHz,CDCl 3):44.41,55.37,111.36,114.50,114.50,118.17,123.39,125.04,126.39,126.46,126.63,127.62,127.77,127.77,127.80,129.16,131.41,131.99,133.04,133.32,136.23,137.18,149.22,158.51,159.61,183.42.
Illustrate 18
1-(2-benzene oxygen ethyl)-5-(4-p-methoxy-phenyl) indole dione
Method is with specification sheets 2, productive rate 75%.
1H-NMR(400MHz,CDCl 3)δ:3.85(3H,s),4.15-4.17(2H,t),4.26-4.28(2H,t),6.83-6.85(2H,d),6.95-6.99(3H,m),7.21-7.45(4H,m),7.47-7.48(2H,d),7.80(2H,d).
13C-NMR(100MHz,CDCl 3):40.31,55.40,65.72,111.47,114.40,114.40,114.52,114.52,118.03,121.49,123.21,127.67,127.67,129.60,129.60,131.50,136.15,137.07,149.97,158.02,158.63,159.63,183.28.
Illustrate 19
1-(4-bromobenzyl)-5-(4-aminomethyl phenyl) indole dione
Getting 5-bromo indole diketone 5g (0.022mol) joins in 50mL round-bottomed flask, in round-bottomed flask, add 15mLN, dinethylformamide, stirring is fully dissolved it, then adds Anhydrous potassium carbonate 9.2g (0.066mol), then, slowly add 4-bromo benzyl bromo 6.6g (0.026mol), under room temperature, react 6h, TLC detects raw material and disappears, stopped reaction.Add 50mL water, use dichloromethane extraction 3 times, merge organic phase, organic phase saturated common salt water washing, anhydrous sodium sulfate drying, with sherwood oil: ethyl acetate=10:1,200-300 order purification by silica gel column chromatography.Obtain 1-(4-bromobenzyl)-5-bromo indole diketone 8.0g, productive rate 88%.
Get 1-(4-bromobenzyl)-5-bromo indole diketone 0.5g (0.0013mol), 4-methylphenylboronic acid 0.19g (0.0014mol), triphenyl phosphorus 0.34g (0.0013mol), palladium 15mg (0.065mmol), Anhydrous potassium carbonate 0.25g (0.0018mol), join in microwave reaction bottle, in microwave reaction bottle, add 20mLN, dinethylformamide.Applying argon gas protection, 120 ℃ of reaction 30min in microwave reactor.After TLC detection reaction is complete, add a small amount of water, use dichloromethane extraction three times, merge organic phase, saturated common salt washing three times for organic phase, organic phase anhydrous sodium sulfate drying, desolventizing, sherwood oil are revolved in decompression: ethyl acetate=5:1200-300 order silicagel column purifying.Obtain 1-(4-bromobenzyl)-5-(4-aminomethyl phenyl) indole dione 0.28g, productive rate 55%.
1H-NMR(400MHz,CDCl 3)δ:2.39(3H,s),4.91(2H,s),6.78-6.80(1H,d),7.24-7.26(4H,d),7.37-7.39(2H,d),7.49-7.51(2H,d),7.68-7.71(1H,m),7.83-7.84(1H,d).
13C-NMR(100MHz,CDCl 3):18.46,21.12,43.59,58.51,111.11,118.11,122.26,123.86,126.40,129.17,129.17,129.81,129.81,132.27,133.56,135.95,136.59,137.67,137.96,149.11,158.37,183.14.
Illustrate 20
1-(4-bromobenzyl)-5-Phenylindole diketone
Get 1-(4-bromobenzyl)-5-bromo indole diketone 0.5g (0.0013mol), phenylo boric acid 0.17g (0.0014mol), triphenyl phosphorus 0.34g (0.0013mol), palladium 15mg (0.065mmol), Anhydrous potassium carbonate 0.25g (0.0018mol), join in microwave reaction bottle, in microwave reaction bottle, add 20mLN, dinethylformamide.Applying argon gas protection, 120 ℃ of reaction 30min in microwave reactor.After TLC detection reaction is complete, add a small amount of water, use dichloromethane extraction three times, merge organic phase, saturated common salt washing three times for organic phase, organic phase anhydrous sodium sulfate drying, desolventizing, sherwood oil are revolved in decompression: ethyl acetate=5:1200-300 order silicagel column purifying.Obtain 1-(4-bromobenzyl)-5-Phenylindole diketone 0.21g, productive rate 42%.
1H-NMR(400MHz,CDCl 3)δ:4.92(2H,s),6.80-6.82(1H,d),7.23-7.26(2H,d),7.37-7.51(7H,m),7.70-7.73(1H,m),7.85-7.86(1H,d).
13C-NMR(100MHz,CDCl 3):43.62,111.11,118.17,122.28,124.03,126.57,126.57,127.99,129.09,129.09,129.17,129.17,132.29,132.29,133.56,136.77,137.70,138.86,149.37,158.33,183.01.
Illustrate 21
1-(4-bromobenzyl)-5-(4-cyano-phenyl) indole dione
Method is with specification sheets 20, productive rate 36%.
1H-NMR(400MHz,CDCl 3)δ:4.93(2H,s),6.85-6.87(1H,d),7.23-7.26(2H,d),7.49-7.51(2H,d),7.58-7.60(2H,d),7.71-7.75(3H,m),7.86(1H,d).
13C-NMR(100MHz,CDCl 3):43.71,111.47,111.78,118.31,118.46,122.43,124.06,127.17,127.17,129.16,129.16,132.36,132.36,132.91,132.91,133.27,135.44,136.83,143.21,150.34,158.10,182.58.
Illustrate 22
1-(4-bromobenzyl)-5-(4-trifluoromethyl) indole dione
Method is with specification sheets 20, productive rate 52%.
1H-NMR(400MHz,CDCl 3)δ:4.93(2H,s),6.84-6.86(1H,d),7.23-7.26(1H,d),7.49-7.51(2H,d),7.58-7.61(2H,d),7.69-7.72(2H,m),7.74-7.79(1H,m),7.86-7.87(1H,d),8.34-8.36(1H,d).
13C-NMR(100MHz,CDCl 3):43.68,111.38,118.24,122.38,124.14,124.86,126.08,126.89,126.89,129.17,129.17,132.34,132.34,133.35,135.95,136.08,136.93,142.31,150.03,158.18,182.78.
Illustrate 23
1-(4-bromobenzyl)-5-(4-tert-butyl-phenyl) indole dione
Method is with specification sheets 20, productive rate 42%.
1H-NMR(400MHz,CDCl 3)δ:1.35(9H,s),4.91(2H,s),6.79-6.81(1H,d),7.23-7.26(2H,d),7.41-7.51(6H,m),7.70-7.72(1H,m),7.85(1H,d).
13C-NMR(100MHz,CDCl 3):31.30,31.30,31.30,34.62,43.61,111.10,118.14,122.26,123.86,126.07,126.07,126.22,126.22,129.19,129.19,132.28,132.28,133.59,135.90,136.62,137.56,149.15,151.19,158.38,183.12.
Illustrate 24
1-(4-methoxy-benzyl)-5-(4-Trifluoromethoxyphen-l) indole dione
Getting 5-bromo indole diketone 5g (0.022mol) joins in 50mL round-bottomed flask, in round-bottomed flask, add 15mLN, dinethylformamide, stirring is fully dissolved it, then adds Anhydrous potassium carbonate 9.2g (0.066mol), then, slowly add 4-methoxy-benzyl chlorine 4.1g (0.026mol), under room temperature, react 6h, TLC detects raw material and disappears, stopped reaction.Add 50mL water, use dichloromethane extraction 3 times, merge organic phase, organic phase saturated common salt water washing, anhydrous sodium sulfate drying, with sherwood oil: ethyl acetate=10:1,200-300 order purification by silica gel column chromatography.Obtain 1-(4-methoxy-benzyl)-5-bromo indole diketone 7.0g, productive rate 85%.
Get 1-(4-methoxy-benzyl)-5-bromo indole diketone 0.5g (0.0014mol), 4-trifluoromethoxy phenylo boric acid 0.35g (0.0017mol), triphenyl phosphorus 0.38g (0.0014mol), palladium 16mg (0.072mmol), Anhydrous potassium carbonate 0.28g (0.002mol), join in microwave reaction bottle, in microwave reaction bottle, add 2mL1,4-dioxane.Applying argon gas protection, 120 ℃ of reaction 30min in microwave reactor.After TLC detection reaction is complete, add a small amount of water, use dichloromethane extraction three times, merge organic phase, saturated common salt washing three times for organic phase, organic phase anhydrous sodium sulfate drying, desolventizing, sherwood oil are revolved in decompression: ethyl acetate=5:1200-300 order silicagel column purifying.Obtain 1-(4-methoxy-benzyl)-5-(4-Trifluoromethoxyphen-l) indole dione, productive rate 51%.
1HNMR(400MHz,CDCl 3)δ3.81(s,3H),4.94(s,2H),6.91(d,2H,J＝8.8Hz),6.94(d,1H,J＝8.4Hz),7.31-7.33(d,2H,J＝8.8Hz),7.60-7.62(d,2H,J＝8.0Hz),7.72(d,2H,J＝8.8Hz),7.74(d,1H,J＝8.4Hz),7.86(s,1H).
13CNMR(100MHz,CDCl 3)δ43.76,55.32,111.57,114.51,114.51,118.24,123.92,126.04,126.08,126.28,126.85,126.85,128.98,128.98,129.84,130.16,135.74,136.80,142.46,150.47,158.19,159.58,183.20.
Illustrate 25
1-(4-methoxy-benzyl)-5-(4-aminomethyl phenyl) indole dione
Get 1-(4-methoxy-benzyl)-5-bromo indole diketone 0.5g (0.0014mol), 4-methylphenylboronic acid 0.24g (0.0017mol), triphenyl phosphorus 0.38g (0.0014mol), palladium 16mg (0.072mmol), Anhydrous potassium carbonate 0.28g (0.002mol), join in microwave reaction bottle, in microwave reaction bottle, add 2mLN, dinethylformamide.Applying argon gas protection, 120 ℃ of reaction 30min in microwave reactor.After TLC detection reaction is complete, add a small amount of water, use dichloromethane extraction three times, merge organic phase, saturated common salt washing three times for organic phase, organic phase anhydrous sodium sulfate drying, desolventizing, sherwood oil are revolved in decompression: ethyl acetate=5:1200-300 order silicagel column purifying.Obtain 1-(4-methoxy-benzyl)-5-(4-aminomethyl phenyl) indole dione, productive rate 55%.
1H-NMR(400MHz,CDCl 3)δ:2.38(3H,s),3.79(3H,s),4.89(2H,s),6.84-6.89(3H,m),7.23-7.25(2H,d),7.28-7.30(2H,d),7.36-7.38(2H,d),7.67-7.69(1H,m),7.81(1H,d).
13C-NMR(100MHz,CDCl 3):21.10,43.66,55.31,111.30,114.44,114.44,118.12,123.66,126.38,126.38,126.50,128.96,128.96,129.77,129.77,136.08,136.48,137.35,137.83,149.55,158.37,159.49,183.56.
Illustrate 26
1-(4-methoxy-benzyl)-5-Phenylindole diketone
Method is with specification sheets 25, productive rate 83%.
1H-NMR(400MHz,CDCl 3)δ:3.78(3H,s),4.89(2H,s),6.86-6.89(3H,m),7.28-7.31(2H,t),7.35-7.37(1H,m),7.41-7.49(4H,m),7.69-7.71(1H,m),7.82(1H,d).
13C-NMR(100MHz,CDCl 3):43.36,55.32,111.36,114.45,114.45,118.13,123.85,126.47,126.55,126.55,127.90,128.98,128.98,129.08,129.08,136.73,137.37,138.96,149.79,158.35,159.50,183.50.
Illustrate 27
1-(4-methoxy-benzyl)-5-(4-cyano-phenyl) indole dione
Method is with specification sheets 25, productive rate 53%.
1H-NMR(400MHz,CDCl 3)δ:3.79(3H,s),4.91(2H,s),6.88-6.90(2H,m),6.91-6.93(1H,d),7.28-7.30(2H,d),7.57-7.60(2H,m),7.70-7.74(3H,m),7.83-7.84(1H,d).
13C-NMR(100MHz,CDCl 3):43.77,55.32,111.60,111.70,114.50,114.50,118.23,118.55,123.89,126.17,127.13,127.13,128.98,128.98,132.89,132.89,135.10,136.77,143.34,150.76,158.11,159.58,183.06.
Illustrate 28
1-(4-methoxy-benzyl)-5-(4-trifluoromethyl) indole dione
Method is with specification sheets 25, productive rate 56%.
1H-NMR(400MHz,CDCl 3)δ:3.81(3H,s),4.94(2H,s),6.90-6.95(3H,t),7.31-7.33(2H,d),7.60-7.62(2H,d),7.70-7.75(3H,m),7.86(1H,d).
13CNMR(100MHz,CDCl 3)δ43.76,55.32,111.57,114.51,114.51,118.24,123.92,126.04,126.08,126.28,126.85,126.85,128.98,128.98,129.84,130.16,135.74,136.80,142.46,150.47,158.19,159.58,183.20.
Illustrate 29
1-(4-methoxy-benzyl)-5-(4-tert-butyl-phenyl) indole dione
Method is with specification sheets 25, productive rate 62%.
1H-NMR(400MHz,CDCl 3)δ:1.35(9H,s),3.79(3H,s),4.90(2H,s),6.85-6.90(3H,m),7.29-7.31(2H,d),7.41-7.47(4H,m),7.69-7.71(1H,m),7.82-7.83(1H,d).
13CNMR(100MHz,CDCl 3)δ31.31,31.31,31.31,34.61,43.67,55.31,111.32,114.45,114.45,118.12,123.66,126.04,126.04,126.19,126.19,126.52,128.99,128.99,136.02,136.54,137.23,149.58,151.07,158.38,159.49,183.58.
Illustrate 30
1-(4-methoxy-benzyl)-5-(4-hydroxy phenyl) indole dione
Method is with specification sheets 25, productive rate 50%.
1H-NMR(400MHz,CDCl 3)δ:3.79(3H,s),4.89(2H,s),6.83-6.85(1H,d),6.87-6.90(4H,m),7.28-7.30(2H,d),7.35-7.37(2H,d),7.62-7.65(1H,m),7.77(1H,d).
13C-NMR(100MHz,CDCl 3):42.91,55.53,112.03,114.53,114.53,116.23,116.23,118.68,121.99,127.80,127.80,127.92,127.92,129.33,129.76,135.61,136.16,149.16,157.73,158.84,159.18,183.78.
Illustrate 31
1-(4-methoxy-benzyl)-5-(4-ethoxyl phenenyl) indole dione
Method is with specification sheets 25, productive rate 59%.
1H-NMR(400MHz,CDCl 3)δ:1.41-1.45(3H,t),3.78(3H,s),4.03-4.09(2H,m),4.89(2H,s),6.82-6.84(1H,d),6.87-6.89(2H,m),6.93-6.95(2H,m),7.28-7.30(2H,d),7.38-7.40(2H,m),7.63-7.66(1H,m),7.77-7.78(1H,d).
13C-NMR(100MHz,CDCl 3):14.82,43.65,55.31,63.59,111.30,114.44,114.44,115.01,115.01,118.11,123.36,126.53,127.60,127.60,128.96,128.96,131.27,136.17,137.13,149.22,158.37,158.94,159.48,183.62.
Illustrate 32
1-(4-methoxy-benzyl)-5-(4-fluorophenyl) indole dione
Method is with specification sheets 25, productive rate 75%.
1H-NMR(400MHz,CDCl 3)δ:3.79(3H,s),4.90(2H,s),6.86-6.89(3H,m),7.10-7.15(2H,m),7.28-7.30(2H,d),7.42-7.45(2H,m),7.63-7.66(1H,m),7.77-7.78(1H,d).
13C-NMR(100MHz,CDCl 3):43.69,55.32,111.41,114.46,114.46,115.92,116.13,118.13,123.69,126.40,128.18,128.26,128.97,128.97,135.13,135.16,136.39,136.54,149.76,158.27,159.52,183.43.
Illustrate 33
1-(4-methoxy-benzyl)-5-(2-p-methoxy-phenyl) indole dione
Method is with specification sheets 25, productive rate 79%.
1H-NMR(400MHz,CDCl 3)δ:3.79(3H,s),3.80(3H,s),4.89(2H,s),6.82-6.84(1H,d),6.87-6.89(2H,m),6.96-7.03(2H,m),7.21-7.23(1H,m),7.29-7.35(3H,m),7.62-7.65(1H,m),7.80(1H,d).
13C-NMR(100MHz,CDCl 3):43.61,55.32,55.51,110.68,111.22,114.42,114.42,117.49,121.03,126.59,126.64,128.23,129.01,129.01,129.37,130.18,134.52,139.26,149.40,156.26,158.49,159.47,183.56.
Illustrate 34
1-(4-methoxy-benzyl)-5-(3-p-methoxy-phenyl) indole dione
Method is with specification sheets 25, productive rate 80%.
1HNMR(400MHz,CDCl 3)δ3.79(s,3H),3.85(s,3H),4.90(s,2H),6.86(d,2H,J＝7.6Hz),6.91(d,2H,J＝8.0Hz),6.99(t,1H),7.05-7.07(d,1H,J＝7.6Hz),7.29-7.31(d,2H,J＝8.0Hz),7.34-7.36(d,1H,J＝7.6Hz),7.69-7.71(d,1H,J＝8.0Hz),7.82(s,1H). 13CNMR(100MHz,CDCl 3)δ43.70,55.32,55.36,111.33,112.31,113.29,114.46,114.46,118.09,118.98,123.90,126.45,128.98,128.98,130.11,136.77,137.22,140.42,149.89,158.35,159.51,160.14,183.50.
Illustrate 35
1-(4-methoxy-benzyl)-5-(3,4-Dimethoxyphenyl) indole dione
Method is with specification sheets 25, productive rate 69%.
1H-NMR(400MHz,CDCl 3)δ:3.79(3H,s),3.91-3.93(6H,d),4.90(2H,s),6.84-6.93(4H,m),6.97-6.98(1H,d),7.02-7.05(1H,m),7.28-7.30(2H,d),7.66-7.68(2H,m),7.79-7.80(1H,d).
13C-NMR(100MHz,CDCl 3):43.67,55.31,56.01,109.71,111.33,111.60,114.44,114.44,118.08,118.90,123.48,126.47,128.96,128.96,131.86,136.35,137.22,149.08,149.39,149.39,158.35,159.49,183.65.
Illustrate 36
1-(4-methoxy-benzyl)-5-(3,5-Dimethoxyphenyl) indole dione
Method is with specification sheets 25, productive rate 74%.
1HNMR(400MHz,CDCl 3)δ3.81(s,3H),3.85(s,6H),4.92(s,2H),6.48(s,1H),6.61(s,2H),6.87-6.91(m,3H),7.30-7.32(d,2H,J＝8.4Hz),7.70-7.72(d,1H,J＝8.0Hz),7.84(s,1H). 13CNMR(100MHz,CDCl 3)δ43.68,55.32,55.48,55.48,99.71,104.83,104.83,111.32,114.45,114.45,118.00,123.84,126.44,128.99,128.99,136.78,137.20,141.02,149.97,158.35,159.50,161.28,161.28,183.50.
Illustrate 37
1-(4-methoxy-benzyl)-5-(3-thiophene) indole dione
Method is with specification sheets 25, productive rate 72%.
1H-NMR(400MHz,CDCl 3)δ:3.79(3H,s),4.89(2H,s),6.82-6.84(1H,d),6.87-6.89(2H,d),7.27-7.30(3H,m),7.37-7.41(2H,m),7.69-7.72(1H,m),7.82(1H,d).
13C-NMR(100MHz,CDCl 3):43.69,55.32,111.38,114.45,114.45,118.07,120.52,123.09,125.68,126.43,127.01,128.96,128.96,132.15,135.87,140.08,149.43,158.30,159.50,183.52.
Illustrate 38
1-(4-methoxy-benzyl)-5-(4-pyridine) indole dione
Method is with specification sheets 25, productive rate 44%.
1HNMR(400MHz,CDCl 3)δ3.79(s,3H),4.92(s,2H),6.88-6.90(d,2H,J＝8.4Hz),6.93-6.95(d,1H,J＝8.4Hz),7.27(d,2H,J＝8.4Hz),7.44-7.45(d,2H,J＝6.0Hz),7.77-7.79(d,1H,J＝8.4Hz),7.90(s,1H),8.67-8.68(d,2H,J＝6.0Hz). 13CNMR(100MHz,CDCl 3)δ43.79,55.33,111.73,114.51,114.51,118.30,120.92,123.73,126.15,128.98,128.98,133.99,136.63,136.63,146.25,150.40,150.40,151.14,158.12,159.59,183.01.
Illustrate 39
1-(4-methoxy-benzyl)-5-(4-methyl-formiate phenyl) indole dione
Method is with specification sheets 25, productive rate 45%.
1H-NMR(400MHz,CDCl 3)δ:3.79(3H,s),3.93(3H,s),4.91(2H,s),6.87-6.91(3H,m),7.28-7.30(2H,d),7.54-7.56(2H,d),7.73-7.75(1H,m),7.86-7.87(1H,d),8.08-8.11(2H,d).
13C-NMR(100MHz,CDCl 3):43.74,52.24,55.32,111.51,114.49,114.49,118.21,123.96,126.30,126.45,126.45,128.97,128.97,129.51,130.38,130.38,136.05,136.82,143.25,150.40,158.23,159.56,166.67,183.25.
Illustrate 40
1-(4-methoxy-benzyl)-4-(4-p-methoxy-phenyl) indole dione
Getting 4-bromo indole diketone 1g (0.0044mol) joins in 50mL round-bottomed flask, in round-bottomed flask, add 4mLN, dinethylformamide, stirring is fully dissolved it, then adds Anhydrous potassium carbonate 1.83g (0.0132mol), then, slowly add 4-methoxy-benzyl chlorine 0.83g (0.0053mol), under room temperature, react 6h, TLC detects raw material and disappears, stopped reaction.Add 15mL water, use dichloromethane extraction 3 times, merge organic phase, organic phase saturated common salt water washing, anhydrous sodium sulfate drying, with sherwood oil: ethyl acetate=10:1,200-300 order purification by silica gel column chromatography.Obtain 1-(4-methoxy-benzyl)-4-bromo indole diketone 1.5g, productive rate 86%.
Get 1-(4-methoxy-benzyl)-4-bromo indole diketone 0.5g (0.0014mol), 4-methoxyphenylboronic acid 0.26g (0.0017mol), triphenyl phosphorus 0.38g (0.0014mol), palladium 16mg (0.072mmol), Anhydrous potassium carbonate 0.28g (0.002mol), join in microwave reaction bottle, in microwave reaction bottle, add 2mLN, dinethylformamide.Applying argon gas protection, 120 ℃ of reaction 30min in microwave reactor.After TLC detection reaction is complete, add a small amount of water, use dichloromethane extraction three times, merge organic phase, saturated common salt washing three times for organic phase, organic phase anhydrous sodium sulfate drying, desolventizing, sherwood oil are revolved in decompression: ethyl acetate=5:1200-300 order silicagel column purifying.Obtain 1-(4-methoxy-benzyl)-4-(4-p-methoxy-phenyl) indole dione 0.32g, productive rate 59%.
1H-NMR(400MHz,CDCl 3)δ:3.79(3H,s),3.87(3H,s),4.89(2H,s),6.71-6.73(1H,d),6.87-6.89(2H,m),6.96-6.98(2H,m),7.01-7.03(1H,d),7.28-7.30(2H,d),7.42-7.46(1H,t),7.48-7.50(2H,m).
13C-NMR(100MHz,CDCl 3):43.52,55.31,55.34,108.96,113.74,113.74,113.83,114.41,114.41,125.61,126.70,128.33,128.90,128.90,130.40,130.40,137.40,143.22,151.50,158.09,159.44,160.53,182.02.
Illustrate 41
1-(4-methoxy-benzyl)-6-(4-p-methoxy-phenyl) indole dione
Getting 6-bromo indole diketone 1g (0.0044mol) joins in 50mL round-bottomed flask, in round-bottomed flask, add 4mLN, dinethylformamide, stirring is fully dissolved it, then adds Anhydrous potassium carbonate 1.83g (0.0132mol), then, slowly add 4-methoxy-benzyl chlorine 0.83g (0.0053mol), under room temperature, react 6h, TLC detects raw material and disappears, stopped reaction.Add 15mL water, use dichloromethane extraction 3 times, merge organic phase, organic phase saturated common salt water washing, anhydrous sodium sulfate drying, with sherwood oil: ethyl acetate=10:1,200-300 order purification by silica gel column chromatography.Obtain 1-(4-methoxy-benzyl)-6-bromo indole diketone 1.6g, productive rate 88%.
Get 1-(4-methoxy-benzyl)-6-bromo indole diketone 0.5g (0.0014mol), 4-methoxyphenylboronic acid 0.26g (0.0017mol), triphenyl phosphorus 0.38g (0.0014mol), palladium 16mg (0.072mmol), Anhydrous potassium carbonate 0.28g (0.002mol), join in microwave reaction bottle, in microwave reaction bottle, add 2mLN, dinethylformamide.Applying argon gas protection, 120 ℃ of reaction 30min in microwave reactor.After TLC detection reaction is complete, add a small amount of water, use dichloromethane extraction three times, merge organic phase, saturated common salt washing three times for organic phase, organic phase anhydrous sodium sulfate drying, desolventizing, sherwood oil are revolved in decompression: ethyl acetate=5:1200-300 order silicagel column purifying.Obtain 1-(4-methoxy-benzyl)-6-(4-p-methoxy-phenyl) indole dione 0.3g, productive rate 52%.
1HNMR(400MHz,CDCl 3)δ3.78(s,3H),3.86(s,3H),4.91(s,2H),6.87-6.89(d,2H,J＝8.4Hz),6.94(s,1H),6.97-6.99(d,2H,J＝8.8Hz),7.24(d,1H,J＝8.0Hz),7.29-7.31(d,2H,J＝8.8Hz),7.44-7.46(d,2H,J＝8.4Hz),7.62-7.64(d,1H,J＝8.0Hz). 13CNMR(100MHz,CDCl 3)δ43.52,55.31,55.45,108.87,114.45,114.45,114.60,114.60,115.96,121.92,125.86,126.71,128.50,128.50,128.93,128.93,131.79,151.12,151.47,158.95,159.46,160.77,182.52.
Illustrate 42
1-(4-methoxy-benzyl)-7-(4-p-methoxy-phenyl) indole dione
Getting 7-bromo indole diketone 1g (0.0044mol) joins in 50mL round-bottomed flask, in round-bottomed flask, add 4mLN, dinethylformamide, stirring is fully dissolved it, then adds Anhydrous potassium carbonate 1.83g (0.0132mol), then, slowly add 4-methoxy-benzyl chlorine 0.83g (0.0053mol), under room temperature, react 6h, TLC detects raw material and disappears, stopped reaction.Add 15mL water, use dichloromethane extraction 3 times, merge organic phase, organic phase saturated common salt water washing, anhydrous sodium sulfate drying, with sherwood oil: ethyl acetate=10:1,200-300 order purification by silica gel column chromatography.Obtain 1-(4-methoxy-benzyl)-7-bromo indole diketone 1.1g, productive rate 63%.
Get 1-(4-methoxy-benzyl)-7-bromo indole diketone 0.5g (0.0014mol), 4-methoxyphenylboronic acid 0.26g (0.0017mol), triphenyl phosphorus 0.38g (0.0014mol), palladium 16mg (0.072mmol), Anhydrous potassium carbonate 0.28g (0.002mol), join in microwave reaction bottle, in microwave reaction bottle, add 2mLN, dinethylformamide.Applying argon gas protection, 120 ℃ of reaction 30min in microwave reactor.After TLC detection reaction is complete, add a small amount of water, use dichloromethane extraction three times, merge organic phase, saturated common salt washing three times for organic phase, organic phase anhydrous sodium sulfate drying, desolventizing, sherwood oil are revolved in decompression: ethyl acetate=5:1200-300 order silicagel column purifying.Obtain 1-(4-methoxy-benzyl)-7-(4-p-methoxy-phenyl) indole dione 0.16g, productive rate 50%.
1H-NMR(400MHz,CDCl 3)δ:3.73(3H,s),3.861(3H,s),4.65(2H,s),6.51-6.53(2H,d),6.62-6.64(2H,d),6.81-6.83(2H,d),6.98-7.00(2H,d),7.07-7.11(1H,m),7.27-7.30(1H,m),7.62-7.64(1H,m).
13C-NMR(100MHz,CDCl 3)δ:44.71,55.25,55.44,113.49,113.49,113.65,113.65,119.30,123.54,124.42,126.99,127.58,127.58,127.76,129.23,130.72,130.72,142.20,147.24,158.87,159.61,159.99,183.62.
Illustrate 43
1-(4-methoxy-benzyl)-5-(4-p-methoxy-phenyl)-3-oximido indolone
Getting 1-(4-methoxy-benzyl)-5-(4-p-methoxy-phenyl) indole dione 0.2g (0.54mmol) joins in 25mL round-bottomed flask, in round-bottomed flask, add 5mL dehydrated alcohol, stirring is fully dissolved it, add again oxammonium hydrochloride 37mg (0.54mmol), back flow reaction 6h, TLC detects raw material and disappears, stopped reaction.Add 15mL water, use dichloromethane extraction 3 times, merge organic phase, organic phase saturated common salt water washing, anhydrous sodium sulfate drying, with sherwood oil: ethyl acetate=10:1,200-300 order purification by silica gel column chromatography.Obtain 1-(4-methoxy-benzyl)-5-(4-p-methoxy-phenyl)-3-oximido indolone, productive rate 63%.
1HNMR(400MHz,DMSO)δ3.71(s,3H),3.78(s,3H),4.90(s,2H),6.89-6.91(d,2H,J＝7.8Hz),6.99-7.01(d,2H,J＝7.8Hz),7.05-7.07(d,1H,J＝8.0Hz),7.29-7.31(d,2H,J＝8.0Hz),7.49-7.51(d,2H,J＝8.0Hz),7.58-7.60(d,1H,J＝8.0Hz),8.20(s,1H),13.63(s,1H). 13CNMR(100MHz,DMSO)δ42.56,55.52,55.63,110.51,114.57,114.57,114.88,114.88,116.42,125.15,127.94,127.94,128.57,129.19,129.19,130.26,132.54,135.32,142.01,143.96,159.11,159.19,163.68.
Illustrate 44
1-(4-methoxy-benzyl)-5-(4-p-methoxy-phenyl)-3-hydroxyindole ketone
Getting 1-(4-methoxy-benzyl)-5-(4-p-methoxy-phenyl) indole dione 0.2g (0.54mmol) joins in 25mL round-bottomed flask, in round-bottomed flask, add 5mL anhydrous methanol, stirring is fully dissolved it, under ice bath, slowly add sodium borohydride 82mg (2.16mmol), room temperature reaction 6h, TLC detects raw material and disappears, stopped reaction.Add 20mL water, use dichloromethane extraction 3 times, merge organic phase, organic phase saturated common salt water washing, anhydrous sodium sulfate drying, with sherwood oil: ethyl acetate=10:1,200-300 order purification by silica gel column chromatography.Obtain 1-(4-methoxy-benzyl)-5-(4-p-methoxy-phenyl)-3-hydroxyindole ketone, productive rate 33%.
1HNMR(400MHz,CDCl 3)δ3.76(s,3H),3.83(s,3H),4.77-4.90(m,2H),5.20(s,1H),6.77-6.79(d,1H,J＝8.0Hz),6.84-6.86(d,2H,J＝8.4Hz),6.93-6.95(d,2H,J＝8.8Hz),7.26(d,2H,J＝8.4Hz),7.38-7.40(d,1H,J＝8.4Hz),7.43-7.45(d,2H,J＝8.8Hz),7.65(s,1H). 13CNMR(100MHz,CDCl 3)δ43.48,55.27,55.35,70.01,109.74,114.26,114.26,114.28,114.28,123.78,127.36,127.50,127.81,127.95,127.95,128.79,128.79,133.12,136.38,141.79,159.05,159.22,176.97.
Illustrate 45
1-(4-methoxy-benzyl)-5-(4-p-methoxy-phenyl)-3,3-contracting dialdehyde indolone
Getting 1-(4-methoxy-benzyl)-5-(4-p-methoxy-phenyl) indole dione 0.5g (1.34mmol) joins in 50mL round-bottomed flask, in round-bottomed flask, add 25mL toluene, stirring is fully dissolved it, add again p-methyl benzenesulfonic acid 23mg (0.13mmol) and ethylene glycol 0.4g (6.7mmol), back flow reaction 8h, TLC detects raw material and disappears, stopped reaction.Add 20mL water, be extracted with ethyl acetate 3 times, merge organic phase, organic phase saturated common salt water washing, anhydrous sodium sulfate drying, with sherwood oil: ethyl acetate=10:1,200-300 order purification by silica gel column chromatography.Obtain 1-(4-methoxy-benzyl)-5-(4-p-methoxy-phenyl)-3,3-contracting dialdehyde indolone, productive rate 53%.
1HNMR(400MHz,CDCl 3)δ3.77(s,3H),3.83(s,3H),4.35-4.38(m,2H),4.63-4.66(m,2H),4.78(s,2H),6.71-6.73(d,1H,J＝8.0Hz),6.84-6.86(d,2H,J＝8.4Hz),6.92-6.94(d,2H,J＝8.8Hz),7.24(d,2H,J＝8.4Hz),7.41(d,1H,J＝8.0Hz),7.42(d,2H,J＝8.8Hz),7.55(s,1H). 13CNMR(100MHz,CDCl 3)δ43.04,55.27,55.34,65.94,65.94,102.39,109.96,114.22,114.22,114.27,114.27,123.39,124.53,127.28,127.80,127.80,128.64,128.64,129.75,132.99,136.55,142.59,159.06,159.18,173.46.
Illustrate 46
1-(4-methoxy-benzyl)-5-(4-p-methoxy-phenyl)-2-indolinone
Getting 1-(4-methoxy-benzyl)-5-(4-p-methoxy-phenyl) indole dione 0.5g (1.34mmol) joins in 25mL round-bottomed flask, in round-bottomed flask, add 5mL dehydrated alcohol, stirring is fully dissolved it, add again hydrazine hydrate 0.13g (2.68mmol), backflow reaction overnight, TLC detects raw material and disappears, stopped reaction.Add 20mL water, be extracted with ethyl acetate 3 times, merge organic phase, organic phase saturated common salt water washing, anhydrous sodium sulfate drying, with sherwood oil: ethyl acetate=10:1,200-300 order purification by silica gel column chromatography.Obtain 1-(4-methoxy-benzyl)-5-(4-p-methoxy-phenyl)-2-indolinone, productive rate 48%.
1HNMR(400MHz,CDCl 3)δ3.65(s,2H),3.77(s,3H),3.83(s,3H),4.87(s,2H),6.77-6.79(d,1H,J＝8.4Hz),6.84-6.86(d,2H,J＝8.8Hz),6.93-6.95(d,2H,J＝8.8Hz),7.27(d,2H,J＝8.4Hz),7.32-7.35(d,1H,J＝8.4Hz),7.42(d,2H,J＝8.8Hz),7.43(s,1H). 13CNMR(100MHz,CDCl 3)δ35.93,43.33,55.27,55.35,109.22,114.18,114.18,114.26,114.26,123.04,125.08,126.20,127.80,127.80,127.99,128.80,128.80,133.50,133.55,143.22,158.93,159.11,175.06.
Illustrate 47
1-(4-methoxy-benzyl)-5-(4-p-methoxy-phenyl)-(3,3-hydroxymethyl) indolone
Getting 1-(4-methoxy-benzyl)-5-(4-p-methoxy-phenyl) indole dione 0.5g (1.34mmol) joins in 25mL round-bottomed flask, in round-bottomed flask, add 5mL anhydrous tetrahydro furan, stirring is fully dissolved it, under ice bath, add methyl-magnesium-bromide 0.3mL (2.68mmol), room temperature reaction 4h, TLC detects raw material and disappears, stopped reaction.Add the 20mL shrend reaction of going out, be extracted with ethyl acetate 3 times, merge organic phase, organic phase saturated common salt water washing, anhydrous sodium sulfate drying, use sherwood oil: ethyl acetate=10:1,200-300 order purification by silica gel column chromatography.Obtain 1-(4-methoxy-benzyl)-5-(4-p-methoxy-phenyl)-(3,3-hydroxymethyl) indolone, productive rate 52%.
1HNMR(400MHz,CDCl 3)δ1.68(s,3H),3.77(s,3H),3.83(s,3H),4.77-4.93(m,2H),6.77-6.79(d,1H,J＝8.4Hz),6.84-6.86(d,2H,J＝8.8Hz),6.93-6.95(d,2H,J＝8.8Hz),7.23-7.25(d,2H,J＝8.4Hz),7.36-7.38(d,1H,J＝8.0Hz),7.43-7.45(d,2H,J＝8.8Hz),7.59(s,1H). 13CNMR(100MHz,CDCl 3)δ25.14,43.32,55.26,55.35,73.87,109.83,114.26,114.26,114.26,114.26,122.09,127.51,127.78,127.82,127.82,128.64,128.64,131.92,133.19,136.40,140.71,159.02,159.16,178.56.
Illustrate 48
1-(4-methoxy-benzyl)-5-(4-p-methoxy-phenyl)-(3,3-difluoro) indolone
Getting 1-(4-methoxy-benzyl)-5-(4-p-methoxy-phenyl) indole dione 0.5g (1.34mmol) joins in 25mL round-bottomed flask, in round-bottomed flask, add 5mL anhydrous methylene chloride, stirring is fully dissolved it, under ice bath, add DAST0.43g (2.68mmol), room temperature reaction 3h, TLC detects raw material and disappears, stopped reaction.Reaction mixture is poured in mixture of ice and water, be extracted with ethyl acetate 3 times, merge organic phase, organic phase saturated common salt water washing, anhydrous sodium sulfate drying, with sherwood oil: ethyl acetate=8:1,200-300 order purification by silica gel column chromatography.Obtain 1-(4-methoxy-benzyl)-5-(4-p-methoxy-phenyl)-(3,3-difluoro) indolone, productive rate 64%.
1HNMR(400MHz,CDCl 3)δ3.78(s,3H),3.84(s,3H),4.85(s,2H),6.82-6.84(d,1H,J＝8.4Hz),6.86-6.88(d,2H,J＝8.4Hz),6.95-6.97(d,2H,J＝8.8Hz),7.26(d,2H,J＝8.4Hz),7.41-7.43(d,2H,J＝8.4Hz),7.51-7.53(d,1H,J＝8.4Hz),7.72(s,1H). 13CNMR(100MHz,CDCl 3)δ43.61,55.30,55.38,110.83,114.44,114.44,114.44,114.44,120.75,123.10,123.10,126.31,127.83,127.83,128.81,128.81,131.48,132.03,137.27,141.67,159.46,159.48,165.46.
Illustrate 49
1-(4-methoxy-benzyl)-5-(4-p-methoxy-phenyl)-3-benzylidene Phenylindole ketone
Getting 1-(4-methoxy-benzyl)-5-(4-p-methoxy-phenyl)-2-indolinone 0.2g (0.56mmol) joins in 25mL round-bottomed flask, in round-bottomed flask, add 5mL anhydrous methylene chloride, stirring is fully dissolved it, under ice bath, add 2 piperidines and phenyl aldehyde 71mg (0.67mmol), back flow reaction 5h, TLC detects raw material and disappears, stopped reaction.Reaction mixture is poured in mixture of ice and water, be extracted with ethyl acetate 3 times, merge organic phase, organic phase saturated common salt water washing, anhydrous sodium sulfate drying, with sherwood oil: ethyl acetate=12:1,200-300 order purification by silica gel column chromatography.Obtain 1-(4-methoxy-benzyl)-5-(4-p-methoxy-phenyl)-3-benzylidene Phenylindole ketone, productive rate 58%.
1HNMR(400MHz,CDCl 3)δ3.78(s,3H),3.81(s,3H),4.96(s,2H),6.78-6.80(d,1H,J＝8.4Hz),6.85-6.91(m,4H),7.28-7.35(m,5H),7.43-7.45(m,3H),7.46-7.48(d,2H,J＝8.4Hz),7.70(s,1H),7.84(s,1H). 13CNMR(100MHz,CDCl 3)δ43.35,55.28,55.34,109.37,114.19,114.19,114.26,114.26,121.27,121.82,127.28,127.56,127.56,128.09,128.13,128.65,128.65,128.76,128.76,129.34,129.34,129.73,133.40,134.82,134.99,137.73,142.25,158.88,159.09,168.60.
Illustrate 50
1-(4-methoxy-benzyl)-5-(4-p-methoxy-phenyl)-3-(4-p-methoxy-phenyl benzylidene) indolone
Method is with specification sheets 49, productive rate 66%.
1HNMR(400MHz,CDCl 3)δ3.77(s,3H),3.82(s,3H),3.88(s,3H),4.96(s,2H),6.78-6.80(d,1H,J＝8.0Hz),6.85-6.87(d,2H,J＝8.0Hz),6.91-6.93(d,2H,J＝8.4Hz),6.98-7.00(d,2H,J＝8.4Hz),7.25-7.35(m,5H),7.70-7.72(d,2H,J＝8.4Hz),7.89(s,1H),7.97(s,1H). 13CNMR(100MHz,CDCl 3)δ43.32,55.28,55.35,55.46,109.29,114.10,114.10,114.17,114.17,114.27,114.27,120.94,122.11,125.28,127.31,127.64,127.64,127.72,128.25,128.74,128.74,131.55,131.55,133.61,134.76,137.93,142.01,158.85,159.05,160.96,168.93.
Illustrate 51
1-(4-methoxy-benzyl)-5-(4-p-methoxy-phenyl)-3-(4-trifluoromethyl benzylidene) indolone
Method is with specification sheets 49, productive rate 49%.
1HNMR(400MHz,CDCl 3)δ3.77(s,3H),3.85(s,3H),4.93(s,2H),6.79-6.81(d,1H,J＝8.0Hz),6.84-6.86(d,2H,J＝8.4Hz),6.97-6.99(d,2H,J＝8.4Hz),7.29(d,2H,J＝8.4Hz),7.38-7.40(d,1H,J＝8.0Hz),7.47-7.49(d,2H,J＝8.4Hz),7.63(s,1H),7.69-7.71(m,3H),8.35-8.37(d,2H,J＝8.0Hz). 13CNMR(100MHz,CDCl 3)δ43.33,55.28,55.36,109.37,114.21,114.21,114.29,114.29,118.01,121.60,121.88,127.28,127.85,127.85,128.04,128.09,128.81,128.81,128.90,128.90,129.65,129.65,130.15,133.50,134.82,134.99,137.75,142.31,158.90,159.06,168.71.
Two, anti-tumor activity test
1. material and instrument
(1) cell strain
Human liver cancer cell (HepG2), human leukemia cell (K562), human colon cancer cell (HT-29)
(2) reagent and instrument
Dimethyl sulfoxide (DMSO) (Amresco company), MTT dry powder (Amresco company), foetal calf serum (Gibco company), trysinization liquid (Hyclone company), DMEM (Hyclone company); CO2gas incubator (Thermo HERAcell 150), clean bench (HS-840 Zhen Tian cleaning apparatus company limited), electronic balance (PB150Z-S Shimadzu International Trading Company Ltd), microscope (Szx-7 Olympus), enzyme linked immunological tester (Thermo MK3).
(3) solution preparation
The preparation of DMEM nutrient solution:
In 500mL Erlenmeyer flask, add DMEM solution 50mL, dual anti-5mL, foetal calf serum 50mL, 1mg/mL mycillin 20mL, is settled to 500mL after fully dissolving, and places 4 ℃ of preservations of refrigerator after degerming.
The preparation of PBS damping fluid:
In 1000mL Erlenmeyer flask, take sodium-chlor 8g, Repone K 0.2g, disodium hydrogen phosphate dodecahydrate 3.15g, potassium primary phosphate 0.24g, is settled to 1000mL after adding the abundant stirring and dissolving of 800mL pure water, places 4 ℃ of preservations of refrigerator after autoclaving.
The preparation of MTT solution:
Take MTT dry powder 0.5g, be dissolved in 100mLPBS damping fluid, after degerming, place 4 ℃ of preservations of refrigerator.
2. method
The nutrient solution that cell cultures is used is the penicillin-Streptomycin sulphate solution containing 1%, the DMEM cell culture fluid of 10% foetal calf serum, and culture condition is 37 ℃, containing 5%CO 2constant incubator.After cell being counted with blood counting chamber, with DMEM nutrient solution, be diluted to 5x10 4individual/mL; In each hole of 96 orifice plates, add 100 μ L cell suspensions, 37 ℃ of incubations of incubator 24 hours; Wanted test compounds is diluted to 5 kinds of concentration: 6mM, 2mM, 0.2mM, 20 μ M, 2 μ M, according to concentration successively dosing 0.5 μ L/ hole, 37 ℃ of incubations of incubator 48 hours; Adding concentration is the MTT of 5mg/mL, 37 ℃ of incubations of incubator 4 hours; Add DMSO by cytolysis, microplate reader is surveyed the OD value under 490nm and 630nm; Processing data, calculates IC according to OD value 50value.
Table 1 different positions substituted indole ketone compounds anti-tumor activity

Claims (10)

1. a different positions substituted indole ketones derivant, is characterized in that: the general structure of derivative is as follows:
Wherein R1 is a kind of of benzyl or alkylate, R2 is a kind of of hydrogen or halogen or aryl compound, R3 is hydrogen or halogen or aryl or five-membered ring or 6-membered heterocyclic compound, R4 is a kind of of hydrogen or halogen or aryl compound, R5 is a kind of of hydrogen or halogen or aryl compound, and R6 is HH or OH or OCH 2cH 2o or NOH or FF or OHCH 3or benzene benzylidene or 4-p-methoxy-phenyl benzylidene or 4 trifluoromethyl benzylidenes is a kind of.
2. different positions substituted indole ketones derivant according to claim 1, it is characterized in that: described R1 is hydrogen, methyl, ethyl, benzyl, 4-chlorobenzyl, 4-luorobenzyl, 4-methoxy-benzyl, 4-bromobenzyl, 4-cyano group benzyl, 3,4-dichloro benzyl, 3, one of 5-dimethyl benzyl, 2-benzene oxygen ethyl, 2-chlorobenzyl, 3-chlorobenzyl, 2-bromobenzyl, 3-bromobenzyl, 2-naphthalene benzyl.
3. different positions substituted indole ketones derivant according to claim 1, is characterized in that: described R2 is one of hydrogen, methyl, methoxyl group, fluorine, chlorine, bromine, iodine, 4-p-methoxy-phenyl.
4. different positions substituted indole ketones derivant according to claim 1, it is characterized in that: described R3 is hydrogen, methyl, methoxyl group, fluorine, chlorine, bromine, iodine, phenyl, 4-p-methoxy-phenyl, 4-Trifluoromethoxyphen-l, 4-aminomethyl phenyl, 4-cyano-phenyl, 4-trifluoromethyl, 4-hydroxy phenyl, 4-tert-butyl-phenyl, 4-fluorophenyl, 4-methyl-formiate phenyl, 3,4-Dimethoxyphenyl, 3, one of 5-Dimethoxyphenyl, 4-ethoxyl phenenyl, 2-p-methoxy-phenyl, 3-p-methoxy-phenyl, 3-thiophene, 4-pyridine.
5. different positions substituted indole ketones derivant according to claim 1, is characterized in that: described R4 is one of hydrogen, methyl, methoxyl group, fluorine, chlorine, bromine, iodine, 4-p-methoxy-phenyl.
6. different positions substituted indole ketones derivant according to claim 1, is characterized in that: described R5 is one of hydrogen, methyl, methoxyl group, fluorine, chlorine, bromine, iodine, 4-p-methoxy-phenyl.Described R6 is HH, OH, OCH 2cH 2o, NOH, FF, OHCH 3, one of benzene benzylidene, 4-p-methoxy-phenyl benzylidene, 4 trifluoromethyl benzylidenes.
7. different positions substituted indole ketones derivant according to claim 1, it is characterized in that: described derivative is 1-methyl-5-(4-p-methoxy-phenyl) indole dione, or 1-ethyl-5-(4-p-methoxy-phenyl) indole dione, or 1-benzyl-5-(4-p-methoxy-phenyl) indole dione, or 1-(4-chlorobenzyl)-5-(4-p-methoxy-phenyl) indole dione, or 1-(2-chlorobenzyl)-5-(4-p-methoxy-phenyl) indole dione, or 1-(3-chlorobenzyl)-5-(4-p-methoxy-phenyl) indole dione, or 1-(4-luorobenzyl)-5-(4-p-methoxy-phenyl) indole dione, or 1-(4-bromobenzyl)-5-(4-p-methoxy-phenyl) indole dione, or 1-(2-bromobenzyl)-5-(4-p-methoxy-phenyl) indole dione, or 1-(3-bromobenzyl)-5-(4-p-methoxy-phenyl) indole dione, or 1-(4-methyl-benzyl)-5-(4-p-methoxy-phenyl) indole dione, or 1-(4-methoxy-benzyl)-5-(4-p-methoxy-phenyl) indole dione, or 1-(4-cyano group benzyl)-5-(4-p-methoxy-phenyl) indole dione, or 1-(4-trifluoromethyl benzyl)-5-(4-p-methoxy-phenyl) indole dione, or 1-(3, 4-dichloro benzyl)-5-(4-p-methoxy-phenyl) indole dione, or 1-(3, 5-dimethyl benzyl)-5-(4-p-methoxy-phenyl) indole dione, or 1-(2-naphthalene benzyl)-5-(4-p-methoxy-phenyl) indole dione, or 1-(2-benzene oxygen ethyl)-5-(4-p-methoxy-phenyl) indole dione, or 1-(4-bromobenzyl)-5-(4-aminomethyl phenyl) indole dione, or 1-(4-bromobenzyl)-5-Phenylindole diketone, or 1-(4-bromobenzyl)-5-(4-cyano-phenyl) indole dione, or 1-(4-bromobenzyl)-5-(4-trifluoromethyl) indole dione, or 1-(4-bromobenzyl)-5-(4-tert-butyl-phenyl) indole dione, or 1-(4-methoxy-benzyl)-5-(4-Trifluoromethoxyphen-l) indole dione, or 1-(4-methoxy-benzyl)-5-(4-aminomethyl phenyl) indole dione, or 1-(4-methoxy-benzyl)-5-Phenylindole diketone, or 1-(4-methoxy-benzyl)-5-(4-cyano-phenyl) indole dione, or 1-(4-methoxy-benzyl)-5-(4-trifluoromethyl) indole dione, or 1-(4-methoxy-benzyl)-5-(4-tert-butyl-phenyl) indole dione, or 1-(4-methoxy-benzyl)-5-(4-hydroxy phenyl) indole dione, or 1-(4-methoxy-benzyl)-5-(4-ethoxyl phenenyl) indole dione, or 1-(4-methoxy-benzyl)-5-(4-fluorophenyl) indole dione, or 1-(4-methoxy-benzyl)-5-(2-p-methoxy-phenyl) indole dione, or 1-(4-methoxy-benzyl)-5-(3-p-methoxy-phenyl) indole dione, or 1-(4-methoxy-benzyl)-5-(3, 4-Dimethoxyphenyl) indole dione, or 1-(4-methoxy-benzyl)-5-(3, 5-Dimethoxyphenyl) indole dione, or 1-(4-methoxy-benzyl)-5-(3-thiophene) indole dione, or 1-(4-methoxy-benzyl)-5-(4-pyridine) indole dione, or 1-(4-methoxy-benzyl)-5-(4-methyl-formiate phenyl) indole dione, or 1-(4-methoxy-benzyl)-4-(4-p-methoxy-phenyl) indole dione, or 1-(4-methoxy-benzyl)-6-(4-p-methoxy-phenyl) indole dione, or 1-(4-methoxy-benzyl)-7-(4-p-methoxy-phenyl) indole dione, or 1-(4-methoxy-benzyl)-5-(4-p-methoxy-phenyl)-3-oximido indolone, or 1-(4-methoxy-benzyl)-5-(4-p-methoxy-phenyl)-3-hydroxyindole ketone, or 1-(4-methoxy-benzyl)-5-(4-p-methoxy-phenyl)-3, 3-contracting dialdehyde indolone, or 1-(4-methoxy-benzyl)-5-(4-p-methoxy-phenyl)-2-indolinone, or 1-(4-methoxy-benzyl)-5-(4-p-methoxy-phenyl)-(3, 3-hydroxymethyl) indolone, or 1-(4-methoxy-benzyl)-5-(4-p-methoxy-phenyl)-(3, 3-difluoro) indolone, or 1-(4-methoxy-benzyl)-5-(4-p-methoxy-phenyl)-3-benzylidene Phenylindole ketone, or 1-(4-methoxy-benzyl)-5-(4-p-methoxy-phenyl)-3-(4-p-methoxy-phenyl benzylidene) indolone, or 1-(4-methoxy-benzyl)-5-(4-p-methoxy-phenyl)-3-(4-trifluoromethyl benzylidene) indolone.
8. a preparation method for the different positions substituted indole ketones derivant as described in one of claim 1 to 7, is characterized in that: route is as follows:
Described R1 is a kind of of benzyl or alkylate, described R2 is a kind of of hydrogen or halogen or aryl compound, described R3 is hydrogen or halogen or aryl or five-membered ring or 6-membered heterocyclic compound, described R4 is a kind of of hydrogen or halogen or aryl compound, described R5 is a kind of of hydrogen or halogen or aryl compound, and described R6 is HH or OH or OCH 2cH 2o or NOH or FF or OHCH 3or benzene benzylidene or 4-p-methoxy-phenyl benzylidene or 4 trifluoromethyl benzylidenes is a kind of.
9. the application of the different positions substituted indole ketones derivant as described in one of claim 1 to 7 in preparing antitumor drug.
10. the application of different positions substituted indole ketones derivant according to claim 9 in preparing antitumor drug, is characterized in that: described antitumor drug is the antitumor drug for the treatment of people liver cancer, human leukemia, human colon carcinoma.
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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105037243A (en) * 2015-06-28 2015-11-11 贵州大学 Paclitaxel side-chain phenyl serine derivative, and preparation method and application thereof
CN106167461A (en) * 2016-07-20 2016-11-30 天津科技大学 A kind of new type water-solubility Isatine derivatives and preparation method and application
CN109574907A (en) * 2017-12-22 2019-04-05 天津科技大学 A kind of indole ketone compound and the preparation method and application thereof
CN111018772A (en) * 2019-11-21 2020-04-17 天津科技大学 5-sulfonamide substituted isatin derivatives with anti-tumor activity

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000033834A1 (en) * 1998-12-04 2000-06-15 Neurosearch A/S Use of isatin derivatives as ion channel activating agents
WO2000064872A1 (en) * 1999-04-23 2000-11-02 Vertex Pharmaceuticals Incorporated INHIBITORS OF c-JUN N-TERMINAL KINASES (JNK)
WO2003069350A2 (en) * 2002-02-12 2003-08-21 Sunesis Pharmaceuticals, Inc. Small molecule modulators of apoptosis
CN102149384A (en) * 2008-08-14 2011-08-10 加拿大贝达药业有限公司 Heterocyclic amide derivatives as EP4 receptor antagonists
CN102892766A (en) * 2010-04-06 2013-01-23 大学健康网络 Kinase inhibitors and method of treating cancer with same
US20130225637A1 (en) * 2012-02-24 2013-08-29 David A. Horne Isatin derivatives, pharmaceutical compositions thereof, and methods of use thereof

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000033834A1 (en) * 1998-12-04 2000-06-15 Neurosearch A/S Use of isatin derivatives as ion channel activating agents
WO2000064872A1 (en) * 1999-04-23 2000-11-02 Vertex Pharmaceuticals Incorporated INHIBITORS OF c-JUN N-TERMINAL KINASES (JNK)
WO2003069350A2 (en) * 2002-02-12 2003-08-21 Sunesis Pharmaceuticals, Inc. Small molecule modulators of apoptosis
CN102149384A (en) * 2008-08-14 2011-08-10 加拿大贝达药业有限公司 Heterocyclic amide derivatives as EP4 receptor antagonists
CN102892766A (en) * 2010-04-06 2013-01-23 大学健康网络 Kinase inhibitors and method of treating cancer with same
US20130225637A1 (en) * 2012-02-24 2013-08-29 David A. Horne Isatin derivatives, pharmaceutical compositions thereof, and methods of use thereof

Non-Patent Citations (13)

* Cited by examiner, † Cited by third party
Title
AHMEDKAMAL,等: "Synthesis and anticancer activity of oxindole derived imidazo[1,5-a]pyrazines", 《EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY》, vol. 46, no. 6, 23 March 2011 (2011-03-23), pages 2427 - 2435, XP028200029, DOI: doi:10.1016/j.ejmech.2011.03.027 *
ALDO ANDREANI,等: "Cytotoxic activities of substituted 3-(3,4,5-trimethoxybenzylidene)-1,3-dihydroindol-2-ones and studies on their mechanisms of action", 《EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY》, vol. 64, 3 April 2013 (2013-04-03), pages 603 - 612, XP028566300, DOI: doi:10.1016/j.ejmech.2013.03.033 *
KAILIN HAN,等: "Design, synthesis and in vitro cytotoxicity evaluation of 5-(2-carboxyethenyl)isatin derivatives as anticancer agents", 《BIOORGANIC & MEDICINAL CHEMISTRY LETTERS》, vol. 24, no. 2, 15 January 2014 (2014-01-15), pages 591 - 594 *
RN：20870-90-0: "《STN Registry数据库》", 16 November 1984, article "CAS RN：20870-90-0" *
RN：552333-04-7: "《STN Registry数据库》", 22 July 2003, article "CAS RN：552333-04-7" *
RN：552333-05-8: "《STN Registry数据库》", 22 July 2003, article "CAS RN：552333-05-8" *
RN：552333-13-8: "《STN Registry数据库》", 22 July 2003, article "CAS RN：552333-13-8" *
RN：881608-86-2: "《STN Registry数据库》", 24 April 2006, article "CAS RN：881608-86-2" *
RN：881609-28-5: "《STN Registry数据库》", 24 April 2006, article "CAS RN：881609-28-5" *
RN：884855-66-7: "《STN Registry数据库》", 18 May 2006, article "CAS RN：884855-66-7" *
RN：913240-15-0: "《STN Registry数据库》", 15 November 2006, article "CAS RN：913240-15-0" *
YICHIN LIU,等: "Discovery of Inhibitors that Elucidate the Role of UCH-L1 Activity in the H1299 Lung Cancer Cell Line", 《CHEMISTRY & BIOLOGY》, vol. 10, no. 9, 30 September 2003 (2003-09-30), pages 837 - 846, XP003005216, DOI: doi:10.1016/j.chembiol.2003.08.010 *
肖锋,等: "3-取代吲哚酮类化合物的合成及抗癌活性研究", 《有机化学》, vol. 29, no. 3, 31 March 2009 (2009-03-31), pages 459 - 461 *

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