CN104016898A - 3,4-disubstituted pyrrole compound as well as preparation method and application thereof - Google Patents
3,4-disubstituted pyrrole compound as well as preparation method and application thereof Download PDFInfo
- Publication number
- CN104016898A CN104016898A CN201410246968.2A CN201410246968A CN104016898A CN 104016898 A CN104016898 A CN 104016898A CN 201410246968 A CN201410246968 A CN 201410246968A CN 104016898 A CN104016898 A CN 104016898A
- Authority
- CN
- China
- Prior art keywords
- pyrroles
- ketone
- phenyl
- methoxy
- pyrrole
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 238000002360 preparation method Methods 0.000 title claims abstract description 113
- -1 3,4-disubstituted pyrrole compound Chemical class 0.000 title claims abstract description 56
- 210000004027 cell Anatomy 0.000 claims abstract description 81
- 150000001875 compounds Chemical class 0.000 claims abstract description 22
- 238000006243 chemical reaction Methods 0.000 claims abstract description 21
- 230000000694 effects Effects 0.000 claims abstract description 18
- 210000004881 tumor cell Anatomy 0.000 claims abstract description 16
- 150000001336 alkenes Chemical class 0.000 claims abstract description 8
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 claims abstract description 8
- 230000005764 inhibitory process Effects 0.000 claims abstract description 5
- 230000035755 proliferation Effects 0.000 claims abstract description 5
- 238000006845 Michael addition reaction Methods 0.000 claims abstract description 4
- 239000002246 antineoplastic agent Substances 0.000 claims abstract description 4
- 229940041181 antineoplastic drug Drugs 0.000 claims abstract description 4
- 238000003379 elimination reaction Methods 0.000 claims abstract description 4
- 238000007363 ring formation reaction Methods 0.000 claims abstract description 4
- CFOAUYCPAUGDFF-UHFFFAOYSA-N tosmic Chemical compound CC1=CC=C(S(=O)(=O)C[N+]#[C-])C=C1 CFOAUYCPAUGDFF-UHFFFAOYSA-N 0.000 claims description 101
- 150000002576 ketones Chemical class 0.000 claims description 57
- LSQARZALBDFYQZ-UHFFFAOYSA-N 4,4'-difluorobenzophenone Chemical compound C1=CC(F)=CC=C1C(=O)C1=CC=C(F)C=C1 LSQARZALBDFYQZ-UHFFFAOYSA-N 0.000 claims description 18
- DRDRZHJTTDSOPK-UHFFFAOYSA-N bis(2-chlorophenyl)methanone Chemical compound ClC1=CC=CC=C1C(=O)C1=CC=CC=C1Cl DRDRZHJTTDSOPK-UHFFFAOYSA-N 0.000 claims description 18
- GNDHXHLGYBJDRD-UHFFFAOYSA-N bis(2-fluorophenyl)methanone Chemical compound FC1=CC=CC=C1C(=O)C1=CC=CC=C1F GNDHXHLGYBJDRD-UHFFFAOYSA-N 0.000 claims description 18
- AZRQQTKALKINGP-UHFFFAOYSA-N dinaphthalen-1-ylmethanone Chemical compound C1=CC=C2C(C(C=3C4=CC=CC=C4C=CC=3)=O)=CC=CC2=C1 AZRQQTKALKINGP-UHFFFAOYSA-N 0.000 claims description 18
- RWCCWEUUXYIKHB-UHFFFAOYSA-N benzophenone Chemical compound C=1C=CC=CC=1C(=O)C1=CC=CC=C1 RWCCWEUUXYIKHB-UHFFFAOYSA-N 0.000 claims description 16
- GUTQMBQKTSGBPQ-UHFFFAOYSA-N dithiophen-2-ylmethanone Chemical compound C=1C=CSC=1C(=O)C1=CC=CS1 GUTQMBQKTSGBPQ-UHFFFAOYSA-N 0.000 claims description 16
- OKISUZLXOYGIFP-UHFFFAOYSA-N 4,4'-dichlorobenzophenone Chemical compound C1=CC(Cl)=CC=C1C(=O)C1=CC=C(Cl)C=C1 OKISUZLXOYGIFP-UHFFFAOYSA-N 0.000 claims description 15
- QBNTVYGGZGPJDZ-UHFFFAOYSA-N bis(3-bromophenyl)methanone Chemical compound BrC1=CC=CC(C(=O)C=2C=C(Br)C=CC=2)=C1 QBNTVYGGZGPJDZ-UHFFFAOYSA-N 0.000 claims description 15
- LFABNOYDEODDFX-UHFFFAOYSA-N bis(4-bromophenyl)methanone Chemical compound C1=CC(Br)=CC=C1C(=O)C1=CC=C(Br)C=C1 LFABNOYDEODDFX-UHFFFAOYSA-N 0.000 claims description 15
- AQLPDLOXKZRZEV-UHFFFAOYSA-N dipyridin-3-ylmethanone Chemical compound C=1C=CN=CC=1C(=O)C1=CC=CN=C1 AQLPDLOXKZRZEV-UHFFFAOYSA-N 0.000 claims description 15
- CLAOXGJAXHTMPM-UHFFFAOYSA-N dipyridin-4-ylmethanone Chemical compound C=1C=NC=CC=1C(=O)C1=CC=NC=C1 CLAOXGJAXHTMPM-UHFFFAOYSA-N 0.000 claims description 15
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 10
- GKQPYCWSUVGAGJ-UHFFFAOYSA-N bis(2-nitrophenyl)methanone Chemical compound [O-][N+](=O)C1=CC=CC=C1C(=O)C1=CC=CC=C1[N+]([O-])=O GKQPYCWSUVGAGJ-UHFFFAOYSA-N 0.000 claims description 9
- QDXRCRVDAMKKDX-UHFFFAOYSA-N bis[4-(aminomethyl)phenyl]methanone Chemical compound C1=CC(CN)=CC=C1C(=O)C1=CC=C(CN)C=C1 QDXRCRVDAMKKDX-UHFFFAOYSA-N 0.000 claims description 9
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 8
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 6
- QPOWUYJWCJRLEE-UHFFFAOYSA-N dipyridin-2-ylmethanone Chemical compound C=1C=CC=NC=1C(=O)C1=CC=CC=N1 QPOWUYJWCJRLEE-UHFFFAOYSA-N 0.000 claims description 6
- 208000032839 leukemia Diseases 0.000 claims description 6
- JWAZRIHNYRIHIV-UHFFFAOYSA-N 2-naphthol Chemical compound C1=CC=CC2=CC(O)=CC=C21 JWAZRIHNYRIHIV-UHFFFAOYSA-N 0.000 claims description 4
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- 239000003795 chemical substances by application Substances 0.000 claims description 4
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- WSBLSUZIPMSRLJ-UHFFFAOYSA-N 1-isocyanoethylsulfonylbenzene Chemical compound [C-]#[N+]C(C)S(=O)(=O)C1=CC=CC=C1 WSBLSUZIPMSRLJ-UHFFFAOYSA-N 0.000 claims description 3
- XNOSMVMRXCUZDN-UHFFFAOYSA-N 3-nitro-4-(3,4,5-trimethoxyphenyl)-1H-pyrrole Chemical class COC1=C(OC)C(OC)=CC(C=2C(=CNC=2)[N+]([O-])=O)=C1 XNOSMVMRXCUZDN-UHFFFAOYSA-N 0.000 claims description 3
- 206010009944 Colon cancer Diseases 0.000 claims description 3
- 241000699802 Cricetulus griseus Species 0.000 claims description 3
- HRAJVYPEPSAHLG-UHFFFAOYSA-N N-[4-(4-nitro-1H-pyrrol-3-yl)phenyl]acetamide Chemical class C1=CC(NC(=O)C)=CC=C1C1=CNC=C1[N+]([O-])=O HRAJVYPEPSAHLG-UHFFFAOYSA-N 0.000 claims description 3
- 206010033128 Ovarian cancer Diseases 0.000 claims description 3
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- XFCTVNAJVQUGEP-UHFFFAOYSA-N ethyl 4-(3,4,5-trimethoxyphenyl)-1H-pyrrole-3-carboxylate Chemical class CCOC(=O)C1=CNC=C1C1=CC(OC)=C(OC)C(OC)=C1 XFCTVNAJVQUGEP-UHFFFAOYSA-N 0.000 claims description 3
- VWDOVYBPDRRKER-UHFFFAOYSA-N ethyl 4-(4-acetamidophenyl)-1H-pyrrole-3-carboxylate Chemical class CCOC(=O)C1=CNC=C1C1=CC=C(NC(C)=O)C=C1 VWDOVYBPDRRKER-UHFFFAOYSA-N 0.000 claims description 3
- GLQKXBIHJPARNA-UHFFFAOYSA-N ethyl 4-pyridin-2-yl-1h-pyrrole-3-carboxylate Chemical class CCOC(=O)C1=CNC=C1C1=CC=CC=N1 GLQKXBIHJPARNA-UHFFFAOYSA-N 0.000 claims description 3
- 201000006585 gastric adenocarcinoma Diseases 0.000 claims description 3
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- 201000001281 rectum adenocarcinoma Diseases 0.000 claims description 3
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- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- 229950011260 betanaphthol Drugs 0.000 claims description 2
- RMMZGPSYPUIIRO-UHFFFAOYSA-N di(thiophen-3-yl)methanone Chemical compound C1=CSC=C1C(=O)C=1C=CSC=1 RMMZGPSYPUIIRO-UHFFFAOYSA-N 0.000 claims description 2
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- 230000000259 anti-tumor effect Effects 0.000 abstract description 5
- PAJALBWYDSQWAV-UHFFFAOYSA-N 1-isocyanosulfonyl-4-methylbenzene Chemical class CC1=CC=C(S(=O)(=O)[N+]#[C-])C=C1 PAJALBWYDSQWAV-UHFFFAOYSA-N 0.000 abstract 1
- 238000000338 in vitro Methods 0.000 abstract 1
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 354
- 239000000047 product Substances 0.000 description 199
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 198
- 238000005481 NMR spectroscopy Methods 0.000 description 187
- 239000007787 solid Substances 0.000 description 98
- 239000002994 raw material Substances 0.000 description 97
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 91
- POUXCZFBIBTXOL-UHFFFAOYSA-N C=CC(=O)C(=O)C(=O)C=C Chemical compound C=CC(=O)C(=O)C(=O)C=C POUXCZFBIBTXOL-UHFFFAOYSA-N 0.000 description 87
- 230000002194 synthesizing effect Effects 0.000 description 87
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- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 238000010025 steaming Methods 0.000 description 1
- 238000011146 sterile filtration Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- BDZBKCUKTQZUTL-UHFFFAOYSA-N triethyl phosphite Chemical compound CCOP(OCC)OCC BDZBKCUKTQZUTL-UHFFFAOYSA-N 0.000 description 1
- 238000006175 van Leusen reaction Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/32—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D207/33—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms with substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D207/333—Radicals substituted by oxygen or sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/32—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D207/33—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms with substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D207/335—Radicals substituted by nitrogen atoms not forming part of a nitro radical
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/34—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/34—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two 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
- C07D207/42—Nitro radicals
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- 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
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- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- 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
- C07D409/06—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 carbon chain containing only aliphatic carbon atoms
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- 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
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
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- Chemical & Material Sciences (AREA)
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- Pyrrole Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a 3,4-disubstituted pyrrole compound. The compound has the following structure shown in a general formula in the specification. A preparation method of the 3,4-disubstituted pyrrole compound comprises a step of performing Michael addition, cyclization and elimination reaction on disubstituted olefin and p-toluenesulfonyl isocyanide. Compared with the prior art, a series of 3,4-disubstituted pyrrole compounds disclosed by the invention have high antitumor activity in vitro; meanwhile, the proliferation inhibition activity to normal cells is inhibited weakly, the excellent tumor cell selectivity is displayed, and the 3,4-disubstituted pyrrole compound can be used as a kind of safe and effective antitumor drugs in the future. The preparation method is convenient to carry out, short in reaction period and high in yield.
Description
Technical field
The present invention relates to organic compound, relate in particular to a kind of 3,4-disubstituted pyrroles compound and its preparation method and application.
Background technology
Tumour be body under various carcinogenic factor effects, the cell of local organization loses the normal regulation to its growth on gene level, causes its clonal abnormality hyperplasia and the abnormality that forms.According to the Chinese tumour registration of < < 2012 annual report > >, show, annual new tumor cases approximately 3,120,000 examples in the whole nation, the average new cancer of people's every days 8550, cancer morbidity is up to 2855.91/10 ten thousand.Although various countries researchist processes and obtains remarkable progress in tumor research and treatment, tumour remains one of mankind's main causes of death at present.In current medical system, oncotherapy often adopt chemotherapy separately or with the method for operative treatment and radiotherapy combined, the huge market requirement is impelled in annual world wide has the antineoplastic compound in a large number with different structure features and action feature to be found, comprising the compound in a large number with pyrroles's mother nucleus structure, their anti-tumor activity has been confirmed and has generally acknowledged, the structure of part of compounds (Journal of Chemistry, 2011,54:8394-8406; Bioorganic & Medicinal Chemistry, 2007,15:17-35; Molecular Pharmacology, 2007,72 (1): 132-140; Journal of Cellular Physiology, 2009,218 (1): 13-21 etc.) as shown in Figure 1.
Due to the specific mechanism of action of antineoplastic compound, these compounds, in killing tumor cell, also seriously affect proper splitting cell conventionally, bring toxic side effects in various degree.For improving sufferer to the tolerance of antineoplastic compound and reducing toxic action, finding can single-minded blocking-up or killing off tumor cells and the antineoplastic compound that do not affect normal cell growth differentiation is a main direction of current tumor research.
Summary of the invention
Object of the present invention, exactly in order to address the above problem, provides a kind of 3,4-disubstituted pyrroles compound and its preparation method and application.
In order to achieve the above object, the present invention has adopted following technical scheme: a kind of 3,4-disubstituted pyrroles compound, has the structure shown in following general formula:
Wherein, R
1=3,4-F
2during Ph, R
2=2-FPhCO, 4-FPhCO, 2-ClPhCO, 4-ClPhCO, 3-BrPhCO, 4-BrPhCO, 3-CH
3oPhCO, 4-CH
3oPhCO, 3-PyridylCO, 4-PyridylCO, 2-ThienylCO, 2-NO
2phCO, PhCO, 1-naphtholCO or 4-biphenylCO;
R
1during=4-CH3CONHPh, R
2=NO
2, CN, COOEt, COCH
3, 2-FPhCO, 4-FPhCO, 2-ClPhCO, 4-ClPhCO, 3-BrPhCO, 4-BrPhCO, 4-CH
3phCO, 2,4-(CH
3)
2phCO, 3-CH
3oPhCO, 4-CH
3oPhCO, 2-pyridylCO, 3-pyridylCO, 4-pyridylCO, 2-thienylCO, PhCO, 1-naphtholCO or 4-biphenylCO;
R
1=3-CH
3during OPh, R
2=2-FPhCO, 4-FPhCO, 2-ClPhCO, 4-ClPhCO, 3-BrPhCO, 4-BrPhCO, 3-CH
3oPhCO, 4-CH
3oPhCO, 3-pyridylCO, 4-pyridylCO, 2-thienylCO, 2-NO
2phCO, PhCO, 1-naphtholCO or 4-biphenylCO;
R
1=3,4-(CH
3o)
2during Ph, R
2=2-FPhCO, 4-FPhCO, 2-ClPhCO, 4-ClPhCO, 3-BrPhCO, 4-BrPhCO, 3-CH
3oPhCO, 4-CH
3oPhCO, 3-pyridylCO, 4-pyridylCO, 2-thienylCO, 2-NO
2phCO, PhCO, 1-naphtholCO or 4-biphenylCO;
R
1=3,4,5-(CH
3o)
3during Ph, R
2=NO
2, CN, COOEt, COCH
3, 2-FPhCO, 4-FPhCO, 2-ClPhCO, 4-ClPhCO, 3-BrPhCO, 4-BrPhCO, 4-CH
3phCO, 2,4-(CH
3)
2phCO, 3-CH
3oPhCO, 4-CH
3oPhCO, 2-pyridylCO, 3-pyridylCO, 4-pyridylCO, 2-thienylCO, 1-naphtholCO or 4-biphenylCO;
R
1during=2-naphthol, R
2=2-FPhCO, 2-ClPhCO, 4-ClPhCO or 2,4-(CH
3)
2phCO;
R
1during=2-pyridyl, R
2=CN, COOEt, 4-CH
3phCO, 2,4-(CH
3)
2phCO, 2-thienylCO, PhCO or 1-naphtholCO.
Above-mentioned 3, the preparation method of 4-disubstituted pyrroles compound, be by disubstituted olefin i with Methyl benzenesulfonyl methyl isocyanide be there is to Michael addition, cyclization and elimination and reacts and obtain, synthetic route is as follows:
In anhydrous response system, add the TosMIC of 1 equivalent disubstituted olefin i and 1.1～1.3 equivalents, add the potassium tert.-butoxide of 1.2～1.4 equivalents as alkaline condensing agent, under low temperature environment, can prepare 3,4-disubstituted pyrroles compound.
In reaction system, add after potassium tert.-butoxide and abundant stirring and dissolving, reaction can be warming up to room temperature and carry out.
Above-mentioned 3, the preparation method of 4-disubstituted pyrroles compound specifically comprises following two steps:
(1) preparation of disubstituted olefin i
R wherein
1group is that starting raw material is introduced by the phenyl aldehyde of various replacements.
The structural formula of the phenyl aldehyde of various replacements as shown in Figure 2.
According to R
2the difference of group, the preparation of i can be divided into following four kinds of situations.
One, work as R
2=NO
2time, take ammonium acetate as condensing agent, the phenyl aldehyde of various replacements (reaction initial concentration 0.1mol/L) is added in Nitromethane 99Min. (simultaneously as reaction solvent), and reflux 4-8h can prepare corresponding replacement nitroolefin, and reaction process is as follows:
But, work as R
2=NO
2, R
1=4-CH
3during CONHPh, reaction solvent is used the Glacial acetic acid that boiling point is higher instead and is more conducive to the carrying out reacting: in Glacial acetic acid, add 4-acetyl-benzaldehyde (reaction initial concentration 0.1mol/L) and appropriate Nitromethane 99Min. reflux, can prepare 1-nitro-2-(4-acetylamino phenyl) ethene under the condensation of ammonium acetate.
Two, work as R
2when=CN or COOEt, with appropriate chloromethyl cyanide and ethyl chloroacetate respectively with the common reflux of triethyl-phosphite (reacting initial concentration 1.5mol/L) directly without γ-ray emission, cooling rear reaction system is purified and is made cyano group and ethoxycarbonyl Horner-Wadsworth-Emmons (HWE) reagent of activation through underpressure distillation respectively, next be jointly dissolved in THF with the phenyl aldehyde of various replacements, under appropriate sodium hydride or potassium tert.-butoxide effect, prepare and replace cyano group alkene and replace ethoxycarbonyl alkene, reaction process is as follows:
Three, work as R
2=COCH
3time, a small amount of sodium Metal 99.5 is joined in anhydrous methanol and prepared containing catalytic amount sodium ethylate (CH
3oNa) methanol solution (or containing the methanol solution that 2-6 drips 10% aqueous sodium hydroxide solution), the phenyl aldehyde of various replacements and proper amount of acetone are added wherein, the reaction initial concentration that makes the phenyl aldehyde of various replacements is 0.1mol/L, and room temperature reaction 2-8h can prepare corresponding replacement ethanoyl alkene;
Four, work as R
2during for substituted benzoyl, preparation method and three similar, adopts the aldol reaction of base catalysis, is about to a small amount of sodium Metal 99.5 and joins in anhydrous methanol and prepare containing catalytic amount CH
3the methanol solution of ONa (or containing the methanol solution that 2-6 drips 10% aqueous sodium hydroxide solution), the phenyl aldehyde of various replacements and proper amount of acetone are added wherein, the reaction initial concentration that makes the phenyl aldehyde of various replacements is 0.1mol/L, room temperature reaction 10min-48h can prepare corresponding disubstituted olefin, its reaction times, reaction process was as follows according to the activity of reaction substrate and sterically hindered difference and there is larger difference:
The structural formula of the substituted acetophenone compound wherein the present invention relates to as shown in Figure 3.
(2) preparation of pyrroles's parent nucleus
THF or the DMSO being dried of take is solvent, and the initial action concentration of disubstituted olefin i is 0.1mol/L.Under the katalysis of appropriate potassium tert.-butoxide, there are Michael addition, cyclization and three steps of elimination with appropriate TosMIC and form pyrrole ring in i, and reaction process is as follows:
Above-mentioned 3, the application of 4-disubstituted pyrroles compound, described 3,4-disubstituted pyrroles compound has proliferation inhibition activity to various tumor cell strains, has the ability of good selective killing tumour cell, can be used for preparing antitumor drug.
Provided by the invention 3,4-disubstituted pyrroles compound has proliferation inhibition activity to 16 kinds of tumor cell lines, especially with comparatively responsive to MGC80-3, DU145, A375, MCF-7, Hela, CHO and CT-26.
16 kinds of tumor cell lines comprise people's gastric adenocarcinoma cells (SGC-7901), gastric carcinoma cells (MGC80-3), National People's Congress's cell lung cancer cell (NCI-H460), Human Prostate Cancer Cells (DU145), human breast cancer cell (MCF-7), human cervical carcinoma cell (Hela), people's malignant melanoma cell (A375), the chronic marrow of people source leukemia (K562), human colon cancer cell (HCT-116), people ties Rectal Adenocarcinoma Cells (HCT-15), human liver cancer cell (Hep G2), human osteosarcoma cell (MG-63), human lung carcinoma cell (A549), mouse leukemia cell (L1210), mouse colonic cell (CT-26) and Chinese hamster ovary cancer cells (CHO), normal cell strain comprises human umbilical vein endothelial cell (HUVEC) and mouse embryo cell (NIH/3T3).
The present invention also finds that 3,4-disubstituted pyrroles compound almost suppresses active to normal cell strain HUVEC and NIH/3T3, has shown selectivity and security that this compounds is good, to being used as antitumor drug safely and effectively.
Described 3,4-disubstituted pyrroles compound comprises (4-(3,4-difluorophenyl)-1H-pyrroles-3-yl) (2-fluorophenyl) ketone, (4-(3,4-difluorophenyl)-1H-pyrroles-3-yl) (4-fluorophenyl) ketone, (4-(3,4-difluorophenyl)-1H-pyrroles-3-yl) (2-chloro-phenyl-) ketone, (4-(3,4-difluorophenyl)-1H-pyrroles-3-yl) (4-chloro-phenyl-) ketone, (4-(3,4-difluorophenyl)-1H-pyrroles-3-yl) (3-bromophenyl) ketone, (4-(3,4-difluorophenyl)-1H-pyrroles-3-yl) (4-bromophenyl) ketone, (4-(3,4-difluorophenyl)-1H-pyrroles-3-yl) (3-p-methoxy-phenyl) ketone, (4-(3,4-difluorophenyl)-1H-pyrroles-3-yl) (4-p-methoxy-phenyl) ketone, (4-(3,4-difluorophenyl)-1H-pyrroles-3-yl) (3-pyridyl) ketone, (4-(3,4-difluorophenyl)-1H-pyrroles-3-yl) (4-pyridyl) ketone, (4-(3,4-difluorophenyl)-1H-pyrroles-3-yl) (2-thienyl) ketone, (4-(3,4-difluorophenyl)-1H-pyrroles-3-yl) (2-nitrophenyl) ketone, (4-(3,4-difluorophenyl)-1H-pyrroles-3-yl) (phenyl) ketone, (4-(3,4-difluorophenyl)-1H-pyrroles-3-yl) (1-naphthyl) ketone, (4-(3,4-difluorophenyl)-1H-pyrroles-3-yl) (4-xenyl) ketone, 3-nitro-4-(4-acetylamino phenyl)-1H-pyrroles, 3-cyano group-4-(4-acetylamino phenyl)-1H-pyrroles, 3-ethoxycarbonyl-4-(4-acetylamino phenyl)-1H-pyrroles, 3-ethanoyl-4-(4-acetylamino phenyl)-1H-pyrroles, (4-(4-acetylamino phenyl)-1H-pyrroles-3-yl) (2-fluorophenyl) ketone, (4-(4-acetylamino phenyl)-1H-pyrroles-3-yl) (4-fluorophenyl) ketone, (4-(4-acetylamino phenyl)-1H-pyrroles-3-yl) (2-chloro-phenyl-) ketone, (4-(4-acetylamino phenyl)-1H-pyrroles-3-yl) (4-chloro-phenyl-) ketone, (4-(4-acetylamino phenyl)-1H-pyrroles-3-yl) (3-bromophenyl) ketone, (4-(4-acetylamino phenyl)-1H-pyrroles-3-yl) (4-bromophenyl) ketone, (4-(4-acetylamino phenyl)-1H-pyrroles-3-yl) (4-aminomethyl phenyl) ketone, (4-(4-acetylamino phenyl)-1H-pyrroles-3-yl) (2,4-3,5-dimethylphenyl) ketone, (4-(4-acetylamino phenyl)-1H-pyrroles-3-yl) (3-p-methoxy-phenyl) ketone, (4-(4-acetylamino phenyl)-1H-pyrroles-3-yl) (4-p-methoxy-phenyl) ketone, (4-(4-acetylamino phenyl)-1H-pyrroles-3-yl) (2-pyridyl) ketone, (4-(4-acetylamino phenyl)-1H-pyrroles-3-yl) (3-pyridyl) ketone, (4-(4-acetylamino phenyl)-1H-pyrroles-3-yl) (4-pyridyl) ketone, (4-(4-acetylamino phenyl)-1H-pyrroles-3-yl) (4-thienyl) ketone, (4-(4-acetylamino phenyl)-1H-pyrroles-3-yl) (phenyl) ketone, (4-(4-acetylamino phenyl)-1H-pyrroles-3-yl) (1-naphthyl) ketone, (4-(4-acetylamino phenyl)-1H-pyrroles-3-yl) (4-xenyl) ketone, (4-(3-p-methoxy-phenyl)-1H-pyrroles-3-yl) (2-fluorophenyl) ketone, (4-(3-p-methoxy-phenyl)-1H-pyrroles-3-yl) (4-fluorophenyl) ketone, (4-(3-p-methoxy-phenyl)-1H-pyrroles-3-yl) (2-chloro-phenyl-) ketone, (4-(3-p-methoxy-phenyl)-1H-pyrroles-3-yl) (4-fluorophenyl) ketone, (4-(3-p-methoxy-phenyl)-1H-pyrroles-3-yl) (3-bromophenyl) ketone, (4-(3-p-methoxy-phenyl)-1H-pyrroles-3-yl) (4-bromophenyl) ketone, (4-(3-p-methoxy-phenyl)-1H-pyrroles-3-yl) (3-p-methoxy-phenyl) ketone, (4-(3-p-methoxy-phenyl)-1H-pyrroles-3-yl) (4-p-methoxy-phenyl) ketone, (4-(3-p-methoxy-phenyl)-1H-pyrroles-3-yl) (3-pyridyl) ketone, (4-(3-p-methoxy-phenyl)-1H-pyrroles-3-yl) (4-pyridyl) ketone, (4-(3-p-methoxy-phenyl)-1H-pyrroles-3-yl) (2-thienyl) ketone, (4-(3-p-methoxy-phenyl)-1H-pyrroles-3-yl) (2-nitrophenyl) ketone, (4-(3-p-methoxy-phenyl)-1H-pyrroles-3-yl) (phenyl) ketone, (4-(3-p-methoxy-phenyl)-1H-pyrroles-3-yl) (1-naphthyl) ketone, (4-(3-p-methoxy-phenyl)-1H-pyrroles-3-yl) (4-xenyl) ketone, (4-(3,4-Dimethoxyphenyl)-1H-pyrroles-3-yl) (2-fluorophenyl) ketone, (4-(3,4-Dimethoxyphenyl)-1H-pyrroles-3-yl) (4-fluorophenyl) ketone, (4-(3,4-Dimethoxyphenyl)-1H-pyrroles-3-yl) (2-chloro-phenyl-) ketone, (4-(3,4-Dimethoxyphenyl)-1H-pyrroles-3-yl) (4-chloro-phenyl-) ketone, (4-(3,4-Dimethoxyphenyl)-1H-pyrroles-3-yl) (3-bromophenyl) ketone, (4-(3,4-Dimethoxyphenyl)-1H-pyrroles-3-yl) (4-bromophenyl) ketone, (4-(3,4-Dimethoxyphenyl)-1H-pyrroles-3-yl) (3-p-methoxy-phenyl) ketone, (4-(3,4-Dimethoxyphenyl)-1H-pyrroles-3-yl) (4-p-methoxy-phenyl) ketone, (4-(3,4-Dimethoxyphenyl)-1H-pyrroles-3-yl) (3-pyridyl) ketone, (4-(3,4-Dimethoxyphenyl)-1H-pyrroles-3-yl) (4-pyridyl) ketone, (4-(3,4-Dimethoxyphenyl)-1H-pyrroles-3-yl) (2-thienyl) ketone, (4-(3,4-Dimethoxyphenyl)-1H-pyrroles-3-yl) (2-nitrophenyl) ketone, (4-(3,4-Dimethoxyphenyl)-1H-pyrroles-3-yl) (phenyl) ketone, (4-(3,4-Dimethoxyphenyl)-1H-pyrroles-3-yl) (1-naphthyl) ketone, (4-(3,4-Dimethoxyphenyl)-1H-pyrroles-3-yl) (4-xenyl) ketone, 3-nitro-4-(3,4,5-trimethoxyphenyl)-1H-pyrroles, 3-cyano group-4-(3,4,5-trimethoxyphenyl)-1H-pyrroles, 3-ethoxycarbonyl-4-(3,4,5-trimethoxyphenyl)-1H-pyrroles, 3-ethanoyl-4-(3,4,5-trimethoxyphenyl)-1H-pyrroles, (4-(3,4,5-trimethoxyphenyl)-1H-pyrroles-3-yl) (2-fluorophenyl) ketone, (4-(3,4,5-trimethoxyphenyl)-1H-pyrroles-3-yl) (4-fluorophenyl) ketone, (4-(3,4,5-trimethoxyphenyl)-1H-pyrroles-3-yl) (2-chloro-phenyl-) ketone, (4-(3,4,5-trimethoxyphenyl)-1H-pyrroles-3-yl) (4-chloro-phenyl-) ketone, (4-(3,4,5-trimethoxyphenyl)-1H-pyrroles-3-yl) (3-bromophenyl) ketone, (4-(3,4,5-trimethoxyphenyl)-1H-pyrroles-3-yl) (4-bromophenyl) ketone, (4-(3,4,5-trimethoxyphenyl)-1H-pyrroles-3-yl) (4-aminomethyl phenyl) ketone, (4-(3,4,5-trimethoxyphenyl)-1H-pyrroles-3-yl) (2,4-3,5-dimethylphenyl) ketone, (4-(3,4,5-trimethoxyphenyl)-1H-pyrroles-3-yl) (3-p-methoxy-phenyl) ketone, (4-(3,4,5-trimethoxyphenyl)-1H-pyrroles-3-yl) (4-p-methoxy-phenyl) ketone, (4-(3,4,5-trimethoxyphenyl)-1H-pyrroles-3-yl) (2-pyridyl) ketone, (4-(3,4,5-trimethoxyphenyl)-1H-pyrroles-3-yl) (3-pyridyl) ketone, (4-(3,4,5-trimethoxyphenyl)-1H-pyrroles-3-yl) (4-pyridyl) ketone, (4-(3,4,5-trimethoxyphenyl)-1H-pyrroles-3-yl) (2-thienyl) ketone, (4-(3,4,5-trimethoxyphenyl)-1H-pyrroles-3-yl) (1-naphthyl) ketone, (4-(3,4,5-trimethoxyphenyl)-1H-pyrroles-3-yl) (4-xenyl) ketone, (4-(2-naphthyl)-1H-pyrroles-3-yl) (2-fluorophenyl) ketone, (4-(2-naphthyl)-1H-pyrroles-3-yl) (2-chloro-phenyl-) ketone, (4-(2-naphthyl)-1H-pyrroles-3-yl) (4-chloro-phenyl-) ketone, (4-(2-naphthyl)-1H-pyrroles-3-yl) (2,4-3,5-dimethylphenyl) ketone, 3-cyano group-4-(2-pyridyl)-1H-pyrroles, 3-ethoxycarbonyl-4-(2-pyridyl)-1H-pyrroles, (4-(2-pyridyl)-1H-pyrroles-3-yl) (4-aminomethyl phenyl) ketone, (4-(2-pyridyl)-1H-pyrroles-3-yl) (2,4-3,5-dimethylphenyl) ketone, (4-(2-pyridyl)-1H-pyrroles-3-yl) (2-thienyl) ketone, (4-(2-pyridyl)-1H-pyrroles-3-yl) (phenyl) ketone and (4-(2-pyridyl)-1H-pyrroles-3-yl) (1-naphthyl) ketone.
The present invention compared with prior art, has following advantage and disadvantage:
1, greatly enriched the kind of 3,4-bit substituent group;
2, the increased kind of tested tumour cell, for find this 3, the antitumor pedigree of 4-disubstituted pyrroles compound provides sufficient basis;
3, increased a kind of normal subject cell NIH/3T3, further confirmed described compound on normal cell without impact conclusion;
4, increased positive control 5 FU 5 fluorouracil, fully to contrast the antitumor application of described compound;
Most importantly, compound of the present invention is obviously better than disclosed polysubstituted pyrrole compound in patent CN 102516149 A to the proliferation inhibition activity of tumour cell.
Accompanying drawing explanation
Fig. 1 is the structural formula of the known antineoplastic compound of part;
Fig. 2 is the structural formula of the phenyl aldehyde of the various replacements that adopt of the present invention;
Fig. 3 is the structural formula of the various substituted acetophenone compounds that adopt of the present invention.
Embodiment
Be below specific embodiments of the invention, technical scheme of the present invention is further described, it is emphasized that the present invention is not limited to these embodiment.In the present invention, abbreviation used and implication thereof are as shown in table 1:
Table 1
| Abbreviation | Chinese implication or full name |
| TosMIC | To Methyl benzenesulfonyl methyl isocyanide |
| THF | Tetrahydrofuran (THF) |
| DMSO | Methyl-sulphoxide |
| t-BuOK | Potassium tert.-butoxide |
| h | Hour |
| eq. | Equivalent |
| rt | Room temperature |
| MTT | 3-(4,5-dimethylthiazole-2)-2,5-phenylbenzene tetrazole bromine salt, tetrazolium bromide |
| IC50 | Half-inhibition concentration (μ mol/L) |
| OD | Absorbancy (Optical Density) |
One, 3,4-disubstituted pyrroles compound synthetic
Embodiment 1
Synthesizing of (4-(3,4-difluorophenyl)-1H-pyrroles-3-yl) (2-fluorophenyl) ketone:
By 1-(2-fluorophenyl)-3-(3,4-difluorophenyl) acrylketone (0.26g, 1.0mmol) with TosMIC (0.21g, 1.1mmol) be dissolved in the THF or DMSO of 10mL drying treatment, under ice bath, stir cooling, slowly or in batches add t-BuOK (0.14g, 1.2mmol), can room temperature reaction after each reactant fully stirs contact.Stopped reaction after 2h, with the excessive t-BuOK of the saturated aqueous ammonium chloride cancellation of ice, reaction solution, with three times (75mL, 25mL * 3) of ethyl acetate extraction, merges organic layer, after saturated common salt water washing once, anhydrous sodium sulphate standing and drying.Pressure reducing and steaming solvent, silica gel column chromatography (sherwood oil: ethyl acetate=1: 2) obtain white (4-(3,4-difluorophenyl)-1H-pyrroles-3-yl) (phenyl) ketone solid (0.19g, 0.64mmol), yield 69.4%.
The experimental data of product is as follows:
1H?NMR(400MHz，DMSO)δ(ppm)：11.82(s，1H，NH)，7.57-7.48(m，3H，-CO-Ar-H)，7.39-7.31(m，2H，-CO-Ar-H+Ar-H)，7.30-7.23(m，2H，Ar-H)，7.19(s，1H，pyrrole-H)，7.16(s，1H，pyrrole-H)；13C?NMR(100MHz，DMSO-d6)δ(ppm)：186.50，159.99，157.53，149.97，149.84，149.26，149.14，147.55，147.43，146.84，146.71，132.46，131.98，131.90，130.31，129.74，129.71，129.43，129.27，125.19，124.16，124.13，122.95，121.36，121.02，117.45，117.28，116.56，116.39，115.98，115.76。
Embodiment 2
Synthesizing of (4-(3,4-difluorophenyl)-1H-pyrroles-3-yl) (4-fluorophenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(4-fluorophenyl)-3-(3,4-difluorophenyl) acrylketone and TosMIC.
Product is micro-yellow solid, yield 83.7%.
The experimental data of product is as follows:
1H?NMR(400MHz，DMSO)δ(ppm)：11.77(s，1H，NH)，7.76(dd，J1＝6.0Hz，J2＝8.4Hz，2H，-CO-Ar-H)，7.48(ddd，J1＝1.6Hz，J2＝8.0Hz，J3＝12Hz，1H，Ar-H)，7.36-7.26(m，4H，Ar-H+-CO-Ar-H+pyrrole-H)，7.25-7.20(m，1H，Ar-H)，7.19(s，1H，pyrrole-H)；13C?NMR(100MHz，DMSO-d6)δ(ppm)：188.79，165.29，162.81，150.08，149.95，149.10，148.97，147.66，147.54，146.68，146.55，136.41，132.77，131.66，131.57，128.57，124.86，123.30，120.41，120.22，117.12，116.94，116.64，116.48，115.19，114.98。
Embodiment 3
Synthesizing of (4-(3,4-difluorophenyl)-1H-pyrroles-3-yl) (2-chloro-phenyl-) ketone
Preparation method is with embodiment 1, and raw material is 1-(2-chloro-phenyl-)-3-(3,4-difluorophenyl) acrylketone and TosMIC.
Product is micro-yellow solid, yield 76.2%.
The experimental data of product is as follows:
1H?NMR(400MHz，DMSO)δ(ppm)：11.81(s，1H，NH)，7.59(dd，J1＝8.0Hz，J2＝12.8Hz，1H，-CO-Ar-H)，7.53-7.44(m，3H，-CO-Ar-H)，7.42(d，J＝6.8Hz，1H，Ar-H)，7.39-7.33(m，2H，Ar-H)，7.16(s，1H，pyrrole-H)，7.02(s，1H，pyrrole-H)；13CNMR(100MHz，DMSO-d6)δ(ppm)：188.48，149.98，149.85，149.30，149.18，147.56，147.43，146.88，146.75，140.52，132.43，130.77，130.59，129.53，128.57，126.80，125.17，122.92，121.30，120.89，117.43，117.25，116.59，116.42。
Embodiment 4
Synthesizing of (4-(3,4-difluorophenyl)-1H-pyrroles-3-yl) (4-chloro-phenyl-) ketone
Preparation method is with embodiment 1, and raw material is 1-(4-chloro-phenyl-)-3-(3,4-difluorophenyl) acrylketone and TosMIC.
Product is faint yellow solid, yield 83.8%.
The experimental data of product is as follows:
1H?NMR(400MHz，DMSO)δ(ppm)：11.79(s，1H，NH)，7.76(d，J＝8.0Hz，2H，-CO-Ar-H)，7.55(d，J＝8.0Hz，2H，-CO-Ar-H)，7.49(dd，J1＝8.0Hz，J2＝12Hz，1H，Ar-H)，7.37-7.27(m，2H，Ar-H+pyrrole-H)，7.26-7.20(m，1H，Ar-H)，7.19(s，1H，pyrrole-H)；13C?NMR(100MHz，DMSO-d6)δ(ppm)：188.93，150.07，149.94，149.14，149.02，147.66，147.53，146.72，146.59，138.57，136.31，132.73，130.74，128.93，128.23，124.96，123.30，120.56，120.07，117.17，117.00，116.64，116.47。
Embodiment 5
Synthesizing of (4-(3,4-difluorophenyl)-1H-pyrroles-3-yl) (3-bromophenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(3-bromophenyl)-3-(3,4-difluorophenyl) acrylketone and TosMIC.
Product is white solid, yield 80.6%.
The experimental data of product is as follows:
1H?NMR(400MHz，DMSO)δ(ppm)：11.80(s，1H，NH)，7.81(s，1H，-CO-Ar-H)，7.78(d，J＝8.0Hz，1H，-CO-Ar-H)，7.72(d，J＝8.0Hz，1H，-CO-Ar-H)，7.50-7.41(m，2H，Ar-H+-CO-Ar-H)，7.36-7.27(m，2H，Ar-H+pyrrole-H)，7.25-7.20(m，1H，Ar-H)，7.19(s，1H，pyrrole-H)；13C?NMR(100MHz，DMSO-d6)δ(ppm)：188.52，150.08，149.95，149.16，149.03，147.66，147.53，146.73，146.61，142.04，134.06，132.68，131.29，130.39，129.13，127.82，124.94，123.35，121.44，120.62，120.00，117.24，117.06，116.64，116.47。
Embodiment 6
Synthesizing of (4-(3,4-difluorophenyl)-1H-pyrroles-3-yl) (4-bromophenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(4-bromophenyl)-3-(3,4-difluorophenyl) acrylketone and TosMIC.
Product is faint yellow solid, yield 92.1%.
The experimental data of product is as follows:
1H?NMR(400MHz，DMSO)δ(ppm)：11.79(s，1H，NH)，7.70(d，J＝8.8Hz，2H，-CO-Ar-H)，7.67(d，J＝8.8Hz，2H，-CO-Ar-H)，7.49(ddd，J1＝2Hz，J2＝8.0Hz，J3＝12.4Hz，1H，Ar-H)，7.36-7.28(m，2H，Ar-H+pyrrole-H)，7.25-7.20(m，1H，Ar-H)，7.18(s，1H，pyrrole-H)；13C?NMR(100MHz，DMSO-d6)δ(ppm)：189.06，150.06，149.94，149.14，149.01，147.65，147.52，146.71，146.59，138.93，132.79，131.18，130.91，128.99，125.29，124.94，123.31，120.58，120.03，117.18，117.00，116.65，116.48。
Embodiment 7
Synthesizing of (4-(3,4-difluorophenyl)-1H-pyrroles-3-yl) (3-p-methoxy-phenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(3-p-methoxy-phenyl)-3-(3,4-difluorophenyl) acrylketone and TosMIC.
Product is faint yellow solid, yield 67.3%.
The experimental data of product is as follows:
1H?NMR(400MHz，DMSO)δ(ppm)：11.79(s，1H，NH)，7.49(ddd，J1＝1.6Hz，J2＝8.0Hz，J3＝12.4Hz，1H，Ar-H)，7.41(t，J＝8.0Hz，1H，-CO-Ar-H)，7.36-7.28(m，3H，-CO-Ar-H+Ar-H+pyrrole-H)，7.26-7.21(m，2H，Ar-H+-CO-Ar-H)，7.17(s，1H，pyrrole-H)，7.16(dd，J1＝2Hz，J2＝8.0Hz，1H，-CO-Ar-H)，3.79(s，3H，-OCH3)；13CNMR(100MHz，DMSO-d6)δ(ppm)：189.85，158.91，150.05，149.93，149.09，148.97，147.64，147.51，146.67，146.54，141.30，132.88，129.25，128.71，124.86，123.31，121.36，120.40，120.31，117.50，117.14，116.97，116.61，116.44，113.60，55.16。
Embodiment 8
Synthesizing of (4-(3,4-difluorophenyl)-1H-pyrroles-3-yl) (4-p-methoxy-phenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(4-p-methoxy-phenyl)-3-(3,4-difluorophenyl) acrylketone and TosMIC.
Product is yellow solid, yield 82.1%.
The experimental data of product is as follows:
1H?NMR(400MHz，DMSO)δ(ppm)：11.68(s，1H，NH)，7.77(d，J＝8.0Hz，2H，-CO-Ar-H)，7.46(ddd，J1＝2Hz，J2＝8.0Hz，J3＝12.4Hz，1H，Ar-H)，7.32-7.23(m，2H，Ar-H+pyrrole-H)，7.22-7.16(m，2H，Ar-H+pyrrole-H)，7.03(d，J＝8.0Hz，2H，-CO-Ar-H)，3.83(s，3H，-OCH3)；13C?NMR(100MHz，DMSO-d6)δ(ppm)：189.09，162.14，150.10，149.97，149.00，148.87，147.68，147.55，146.58，146.45，133.01，132.23，131.27，127.49，124.71，123.14，120.52，120.01，116.89，116.72，116.67，116.50，113.42，55.37。
Embodiment 9
Synthesizing of (4-(3,4-difluorophenyl)-1H-pyrroles-3-yl) (3-pyridyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(3-pyridyl)-3-(3,4-difluorophenyl) acrylketone and TosMIC.
Product is yellow solid, yield 38.3%.
The experimental data of product is as follows:
1H?NMR(400MHz，DMSO)δ(ppm)：11.89(s，1H，NH)，8.73(d，J＝4.8Hz，2H，-CO-Ar-H)，7.60(d，J＝4.8Hz，2H，-CO-Ar-H)，7.54(ddd，J1＝2Hz，J2＝8.0Hz，J3＝12.4Hz，1H，Ar-H)，7.36-7.25(m，3H，Ar-H+pyrrole-H)，7.20(s，1H，pyrrole-H)；13C?NMR(100MHz，DMSO-d6)δ(ppm)：188.76，150.46，150.38，149.93，149.37，149.27，147.61，147.48，146.84，146.73，132.53，130.31，125.11，123.33，122.27，121.11，119.58，117.43，117.26，116.62，116.46。
Embodiment 10
Synthesizing of (4-(3,4-difluorophenyl)-1H-pyrroles-3-yl) (4-pyridyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(4-pyridyl)-3-(3,4-difluorophenyl) acrylketone and TosMIC.
Product is yellow solid, yield 56.1%.
The experimental data of product is as follows:
1H?NMR(400MHz，DMSO)δ(ppm)：11.86(s，1H，NH)，8.86(s，1H，-CO-Ar-H)，8.75(d，J＝4Hz，1H，-CO-Ar-H)，8.08(d，J＝8.0Hz，1H，-CO-Ar-H)，7.54-7.47(m，2H，-CO-Ar-H+Ar-H)，7.37(s，1H，pyrrole-H)，7.35-7.23(m，2H，Ar-H)，7.20(s，1H，pyrrole-H)；13C?NMR(100MHz，DMSO-d6)δ(ppm)：188.46，151.84，150.06，149.94，149.38，149.19，149.06，147.64，147.52，146.77，146.64，136.25，135.43，132.62，129.55，125.03，123.37，123.32，120.80，120.23，117.34，117.17，116.63，116.47。
Embodiment 11
Synthesizing of (4-(3,4-difluorophenyl)-1H-pyrroles-3-yl) (2-thienyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(2-thienyl)-3-(3,4-difluorophenyl) acrylketone and TosMIC.
Product is faint yellow solid, yield 53.9%.
The experimental data of product is as follows:
1H?NMR(400MHz，DMSO)δ(ppm)：11.77(s，1H，NH)，7.96(d，J＝4Hz，1H，-CO-Ar-H)，7.76(d，J＝4Hz，1H，-CO-Ar-H)，7.58(s，1H，pyrrole-H)，7.48(ddd，J1＝2Hz，J2＝8.0Hz，J3＝12.4Hz，1H，Ar-H)，7.37(dd，J1＝8.0Hz，J2＝18Hz，1H，Ar-H)，7.24-7.18(m，3H，-CO-Ar-H+Ar-H+pyrrole-H)；13C?NMR(100MHz，DMSO-d6)δ(ppm)：181.67，150.13，150.00，149.10，148.97，147.71，147.58，146.67，146.55，145.33，133.41，133.06，132.76，128.24，127.21，124.76，122.93，120.35，120.06，116.91，116.74，116.58。
Embodiment 12
Synthesizing of (4-(3,4-difluorophenyl)-1H-pyrroles-3-yl) (2-nitrophenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(2-nitrophenyl)-3-(3,4-difluorophenyl) acrylketone and TosMIC.
Product is faint yellow solid, yield 75.9%.
The experimental data of product is as follows:
1H?NMR(400MHz，DMSO)δ(ppm)：11.82(s，1H，NH)，8.15(d，J＝7.6Hz，1H，-CO-Ar-H)，7.85(t，J＝7.6Hz，1H，-CO-Ar-H)，8.76(t，J＝7.6Hz，1H，-CO-Ar-H)，7.65(d，J＝7.6Hz，1H，-CO-Ar-H)，7.57(ddd，J1＝2Hz，J2＝8.0Hz，J3＝12.4Hz，1H，Ar-H)，7.41-7.31(m，2H，Ar-H)，7.17(s，1H，pyrrole-H)，7.10(s，1H，pyrrole-H)；13C?NMR(100MHz，DMSO-d6)δ(ppm)：187.05，150.02，149.90，149.32，149.19，147.60，147.48，146.89，146.76，146.71，136.79，134.01，132.31，130.61，129.77，129.15，124.96，124.27，122.90，121.31，120.53，117.22，117.05，116.68，116.51。
Embodiment 13
Synthesizing of (4-(3,4-difluorophenyl)-1H-pyrroles-3-yl) (phenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(phenyl)-3-(3,4-difluorophenyl) acrylketone and TosMIC.
Product is white solid, yield 70.8%.
The experimental data of product is as follows:
1H?NMR(400MHz，DMSO)δ(ppm)：11.74(s，1H，NH)，7.75(d，J＝7.6Hz，2H，-CO-Ar-H)，7.60(t，J＝7.6Hz，1H，-CO-Ar-H)，7.52-7.42(m，3H，-CO-Ar-H+Ar-H)，7.35(dd，J1＝8.8Hz，J2＝20.8Hz，1H，Ar-H)，7.27-7.20(m，2H，pyrrole-H+Ar-H)，7.18(s，1H，pyrrole-H)；13C?NMR(100MHz，DMSO-d6)δ(ppm)：190.99，147.90，147.37，139.02，133.15，130.11，129.81，129.70，128.50，127.39，126.63，126.13，125.80，125.30，125.14，124.59，122.14，120.03，112.91，119.57，111.42，55.53，55.27。
Embodiment 14
Synthesizing of (4-(3,4-difluorophenyl)-1H-pyrroles-3-yl) (1-naphthyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(1-naphthyl)-3-(3,4-difluorophenyl) acrylketone and TosMIC.
Product is micro-yellow solid, yield 81.5%.
The experimental data of product is as follows:
1H?NMR(400MHz，DMSO)δ(ppm)：11.83(s，1H，NH)，8.28(m，1H，-CO-Ar-H)，8.18(m，1H，-CO-Ar-H)，7.65-7.40(m，6H，-CO-Ar-H+Ar-H)，7.38-7.28(m，2H，Ar-H+pyrrole-H)，7.27-7.21(m，1H，Ar-H)，7.18(s，1H，pyrrole-H)；13C?NMR(100MHz，DMSO-d6)δ(ppm)：191.05，150.03，149.90，149.31，149.19，147.61，147.48，146.88，146.76，138.82，133.04，132.31，130.11，129.97，129.50，128.11，126.63，126.12，125.98，125.23，125.16，124.96，124.57，122.02，119.75，117.22，117.05，116.68，116.52。
Embodiment 15
Synthesizing of (4-(3,4-difluorophenyl)-1H-pyrroles-3-yl) (4-xenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(4-xenyl)-3-(3,4-difluorophenyl) acrylketone and TosMIC.
Product is white solid, yield 48.3%.
The experimental data of product is as follows:
1H?NMR(400MHz，DMSO)δ(ppm)：11.76(s，1H，NH)，7.85(d，J＝8.0Hz，2H，-CO-Ar-H)，7.80(d，J＝8.0Hz，2H，-CO-Ar-H)，7.75(d，J＝8.0Hz，2H，-CO-Ar-H)，7.54-7.40(m，4H，-CO-Ar-H+Ar-H)，7.37-7.29(m，2H，Ar-H+pyrrole-H)，7.28-7.22(m，1H，Ar-H)，7.20(s，1H，pyrrole-H)；13C?NMR(100MHz，DMSO-d6)δ(ppm)：190.21，150.06，149.93，149.09，148.97，147.64，147.52，146.67，146.54，139.90，132.88，131.52，128.88，128.68，128.13，124.87，123.29，120.39，120.35，117.14，116.96，116.62，116.45。
Embodiment 16
3-nitro-4-(4-acetylamino phenyl)-1H-pyrroles's is synthetic
Preparation method is with embodiment 1, and raw material is 1-acetylaminohydroxyphenylarsonic acid 4-(2-nitroethylene base) benzene and TosMIC.
Product is brown solid, yield 39.1%.
The experimental data of product is as follows:
1H?NMR(300MHz，DMSO-d6)δ(ppm)：12.04(s，1H，pyrrole-NH)，9.96(s，1H，PhNH-)，7.93(dd，J1＝3.0Hz，J2＝1.8Hz，1H，pyrrole?H)，7.56(d，J＝9.0Hz，2H，ArH)，7.32(d，J＝9.0Hz，2H，ArH)，6.93(t，J＝3.0Hz，1H，pyrrole?H)，2.04(s，3H，-COCH3)；13C?NMR(100MHz，DMSO-d6)δ(ppm)：168.20，138.12，133.37，129.31(2C)，127.26，122.72，119.84，119.29，118.40(2C)，23.98。
Embodiment 17
3-cyano group-4-(4-acetylamino phenyl)-1H-pyrroles's is synthetic
Preparation method is with embodiment 1, and raw material is 3-(4-acetylamino phenyl) vinyl cyanide and TosMIC.
Product is white solid, yield 49.7%.
The experimental data of product is as follows:
1H?NMR(400MHz，DMSO-d6)δ(ppm)：11.86(s，1H，pyrrole-NH)，9.98(s，1H，PhNH-)，7.67(dd，J1＝4.0Hz，J2＝2.0Hz，1H，pyrrole?H)，7.62(d，J＝8.0Hz，2H，ArH)，7.56(d，J＝8.0Hz，2H，ArH)，7.24(t，J＝4.0Hz，1H，pyrrole?H)，2.06(s，3H，-COCH3)；13C?NMR(100MHz，DMSO-d6)δ(ppm)：168.18，137.93，128.37，128.00，126.14(2C)，124.93，119.27(2C)，117.54，117.10，89.07，23.95。
Embodiment 18
3-ethoxycarbonyl-4-(4-acetylamino phenyl)-1H-pyrroles's is synthetic
Preparation method is with embodiment 1, and raw material is 3-(4-acetamido phenyl) ethyl propenoate and TosMIC.
Product is white solid, yield 51.6%.
The experimental data of product is as follows:
1H?NMR(300MHz，DMSO-d6)δ(ppm)：11.48(s，1H，pyrrole-NH)，9.87(s，1H，PhNH-)，7.50(d，J＝9.0Hz，2H，ArH)，7.43(t，J＝3.0Hz，1H，pyrrole?H)，7.35(d，J＝9.0Hz，2H，ArH)，6.83(t，J＝3.0Hz，1H，pyrrole?H)，4.08(dd，J1＝12.0Hz，J2＝6.0Hz，2H，-COOCH2-)，1.17(t，J＝6.0Hz，3H，-CH3)，2.03(s，3H，-COCH3)；13C?NMR(100MHz，DMSO-d6)δ(ppm)：168.03，164.13，137.27，129.83，128.98(2C)，125.70，124.84，118.68，118.20(2C)，111.88，58.67，23.96，14.25。
Embodiment 19
3-ethanoyl-4-(4-acetylamino phenyl)-1H-pyrroles's is synthetic
Preparation method is with embodiment 1, and raw material is 4-(4-acetylamino phenyl)-3-butene-2-one and TosMIC.
Product is white solid, yield 78.6%.
The experimental data of product is as follows:
1H?NMR(400MHz，DMSO-d6)δ(ppm)：11.49(s，1H，pyrrole-NH)，9.86(s，1H，PhNH-)，7.66(dd，J1＝4.0Hz，J2＝2.0Hz，1H，pyrrole?H)，7.48(d，J＝8.0Hz，2H，ArH)，7.33(d，J＝8.0Hz，2H，ArH)，6.87(t，J＝4.0Hz，1H，pyrrole?H)，2.31(s，3H，-COCH3)，2.04(s，3H，-NHCOCH3)；13C?NMR(100MHz，DMSO-d6)δ(ppm)：192.53，167.99，137.20，130.30，128.96(2C)，127.36，124.11，121.89，119.41，118.24(2C)，28.24，23.94。
Embodiment 20
Synthesizing of (4-(4-acetylamino phenyl)-1H-pyrroles-3-yl) (2-fluorophenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(2-fluorophenyl)-3-(4-acetylamino phenyl) acrylketone and TosMIC.
Product is white solid, yield 63.9%.
The experimental data of product is as follows:
1H?NMR(300MHz，DMSO-d6)δ(ppm)：11.67(s，1H，pyrrole-NH)，9.90(s，1H，PhNH-)，7.56-7.52(m，1H，ArH)，7.50(d，J＝9.0Hz，2H，ArH)，7.475-7.44(m，1H，ArH)，7.39(d，J＝9.0Hz，2H，ArH)，7.25(t，J＝9.0Hz，2H，ArH)，7.11(t，J＝3.0Hz，1H，pyrrole?H)，7.00(t，J＝3.0Hz，1H，pyrrole?H)，2.04(s，3H，-COCH3)；13C?NMR(100MHz，DMSO-d6)δ(ppm)：186.44，168.04，158.77(1C，JCF＝247.4Hz)，137.36，131.78(1C，JCF＝8.3Hz)，129.88，129.69，129.62(1C，JCF＝8.9Hz)，129.53，128.79(2C)，124.88，124.11(1C，JCF＝3.3Hz)，121.43，119.95，118.28(2C)，115.85(1C，JCF＝21.8Hz)，23.97。
Embodiment 21
Synthesizing of (4-(4-acetylamino phenyl)-1H-pyrroles-3-yl) (4-fluorophenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(4-fluorophenyl)-3-(4-acetylamino phenyl) acrylketone and TosMIC.
Product is white solid, yield 90.6%.
The experimental data of product is as follows:
1H?NMR(300MHz，DMSO-d6)δ(ppm)：11.62(s，1H，pyrrole-NH)，9.86(s，1H，PhNH-)，7.81-7.30(m，2H，ArH)，7.45(d，J＝9.0Hz，2H，ArH)，7.30-7.18(m，5H)，7.03(t，J＝3.0Hz，1H，pyrrole?H)，2.01(s，3H，-COCH3)；13C?NMR(100MHz，DMSO-d6)δ(ppm)：188.94，168.01，163.98(1C，JCF＝249.2Hz)，137.13，136.51(1C，JCF＝2.7Hz)，131.62(2C，JCF＝9.0Hz)，129.91，128.47(2C)，127.87，125.16，120.28，119.21，118.46(2C)，115.03(2C，JCF＝21.6Hz)，23.94。
Embodiment 22
Synthesizing of (4-(4-acetylamino phenyl)-1H-pyrroles-3-yl) (2-chloro-phenyl-) ketone
Preparation method is with embodiment 1, and raw material is 1-(2-chloro-phenyl-)-3-(4-acetylamino phenyl) acrylketone and TosMIC.
Product is white solid, yield 93.9%.
The experimental data of product is as follows:
1H?NMR(300MHz，DMSO-d6)δ(ppm)：11.65(s，1H，pyrrole-NH)，9.90(s，1H，PhNH-)，7.53-7.36(m，8H)，6.99(t，J＝3.0Hz，1H，pyrrole?H)，6.93(dd，J1＝3.0Hz，J2＝1.8Hz，1H，pyrrole?H)，2.03(s，3H，-COCH3)；13C?NMR(100MHz，DMSO-d6)δ(ppm)：188.37，168.07，140.79，137.43，130.43，130.37，129.54(2C)，129.51，128.81(2C)，128.52，126.77，124.89，120.93，120.22，118.30(2C)，23.98。
Embodiment 23
Synthesizing of (4-(4-acetylamino phenyl)-1H-pyrroles-3-yl) (4-chloro-phenyl-) ketone
Preparation method is with embodiment 1, and raw material is 1-(4-chloro-phenyl-)-3-(4-acetylamino phenyl) acrylketone and TosMIC.
Product is white solid, yield 90.0%.
The experimental data of product is as follows:
1H?NMR(300MHz，DMSO-d6)δ(ppm)：11.64(s，1H，pyrrole-NH)，9.87(s，1H，PhNH-)，7.73(d，J＝9.0Hz，2H，ArH)，7.51(d，J＝9.0Hz，2H，ArH)，7.46(d，J＝9.0Hz，2H，ArH)，7.28(d，J＝9.0Hz，2H，ArH)，7.23(t，J＝3.0Hz，1H，pyrrole?H)，7.03(t，J＝3.0Hz，1H，pyrrole?H)，2.01(s，3H，-COCH3)；13C?NMR(100MHz，DMSO-d6)δ(ppm)：189.04，168.01，138.69，137.18，136.20，130.75(2C)，129.83，128.51(2C)，128.25，128.19(2C)，125.17，120.13，119.36，118.44(2C)，23.95。
Embodiment 24
Synthesizing of (4-(4-acetylamino phenyl)-1H-pyrroles-3-yl) (3-bromophenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(3-bromophenyl)-3-(4-acetylamino phenyl) acrylketone and TosMIC.
Product is white solid, yield 77.8%.
The experimental data of product is as follows:
1H?NMR(300MHz，DMSO-d6)δ(ppm)：11.67(s，1H，pyrrole-NH)，9.88(s，1H，PhNH-)，7.76(m，1H，ArH)，7.69(m，1H，ArH)，7.62(m，1H，ArH)，7.44(d，J＝9.0Hz，2H，ArH)，7.40(t，J＝9.0Hz，1H，ArH)，7.26(d，J＝9.0Hz，2H，ArH)，7.25-7.21(m，1H，pyrrole?H)，7.03(t，J＝3.0Hz，1H，pyrrole?H)，2.01(s，3H，-COCH3)；13C?NMR(100MHz，DMSO-d6)δ(ppm)：188.61，168.00，142.16，137.22，134.00，131.28，130.36，129.75，128.54(2C)，128.53，127.86，125.22，121.44，120.00，119.46，118.41(2C)，23.96。
Embodiment 25
Synthesizing of (4-(4-acetylamino phenyl)-1H-pyrroles-3-yl) (4-bromophenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(4-bromophenyl)-3-(4-acetylamino phenyl) acrylketone and TosMIC.
Product is white solid, yield 89.7%.
The experimental data of product is as follows:
1H?NMR(300MHz，DMSO-d6)δ(ppm)：11.64(s，1H，pyrrole-NH)，9.87(s，1H，PhNH-)，7.64(s，4H，ArH)，7.44(d，J＝9.0Hz，2H，ArH)，7.27(d，J＝9.0Hz，2H，ArH)，7，23(t，J＝3.0Hz，1H，pyrrole?H)，7.03(t，J＝3.0Hz，1H，pyrrole?H)，2.01(s，3H，-COCH3)；13C?NMR(100MHz，DMSO-d6)δ(PPm)：189.17，168.01，139.05，137.19，131.14(2C)，130.92(2C)，129.82，128.51(2C)，128.31，125.20，125.17，120.08，119.38，118.43(2C)，23.96。
Embodiment 26
Synthesizing of (4-(4-acetylamino phenyl)-1H-pyrroles-3-yl) (4-aminomethyl phenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(4-aminomethyl phenyl)-3-(4-acetylamino phenyl) acrylketone and TosMIC.
Product is white solid, yield 79.7%.
The experimental data of product is as follows:
1H?NMR(300MHz，DMSO-d6)δ(ppm)：11.55(s，1H，pyrrole-NH)，9.87(s，1H，PhNH-)，7.63(d，J＝6.0Hz，2H，ArH)，7.44(d，J＝6.0Hz，2H，ArH)，7.27(d，J＝6.0Hz，2H，ArH)，7.23(d，J＝6.0Hz，2H，ArH)，7.16(dd，J1＝3.0Hz，J2＝0.9Hz，1H，pyrrole?H)，7.01(t，J＝3.0Hz，1H，pyrrole?H)，2.35(s，3H，-PhCH3)，2.01(s，3H，-COCH3)；13C?NMR(100MHz，DMSO-d6)δ(ppm)：190.05，168.00，141.55，137.31，137.07，130.08，129.14(2C)，128.67(2C)，128.39(2C)，127.58，125.08，120.50，119.05，118.48(2C)，23.94，21.02
Embodiment 27
Synthesizing of (4-(4-acetylamino phenyl)-1H-pyrroles-3-yl) (2,4-3,5-dimethylphenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(2,4-3,5-dimethylphenyl)-3-(4-acetylamino phenyl) acrylketone and TosMIC.
Product is white solid, yield 80.8%.
The experimental data of product is as follows:
1H?NMR(300MHz，DMSO-d6)δ(ppm)：11.52(s，1H，pyrrole-NH)，9.88(s，1H，PhNH-)，7.27(d，J＝9.0Hz，2H，ArH)，7.36(d，J＝9.0Hz，2H，ArH)，7.23(d，J＝9.0Hz，1H，ArH)，7.05(s，1H，ArH)，7.00(d，J＝9.0Hz，1H，ArH)，6.96(s，1H，pyrrole?H)，6.88(t，J＝3.0Hz，1H，pyrrole?H)，2.29(s，3H，PhCH3)，2.20(s，3H，PhCH3)，2.02(s，3H，-COCH3)；13C?NMR(100MHz，DMSO-d6)δ(ppm)：192.19，168.01，138.65，138.50，137.22，135.21，131.10，129.93，129.30，128.68(2C)，127.96，125.45，124.88，121.91，119.66，118.32(2C)，23.96，20.80，19.36。
Embodiment 28
Synthesizing of (4-(4-acetylamino phenyl)-1H-pyrroles-3-yl) (3-p-methoxy-phenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(3-p-methoxy-phenyl)-3-(4-acetylamino phenyl) acrylketone and TosMIC.
Product is yellow solid, yield 62.0%.
The experimental data of product is as follows:
1H?NMR(300MHz，DMSO-d6)δ(ppm)：11.59(s，1H，pyrrole-NH)，9.87(s，1H，PhNH-)，7.44(d，J＝9.0Hz，2H，ArH)，7.35(t，J＝9.0Hz，1H，ArH)，7.29(m，1H，ArH)，7.27(d，J＝9.0Hz，2H，ArH)，7.21(m，1H，ArH)，7.19(t，J＝3.0Hz，1H，pyrrole?H)，7.10(m，1H，ArH)，7.01(t，J＝3.0Hz，1H，pyrrole?H)，3.75(s，3H，PhOCH3)，2.01(s，3H，-COCH3)；13C?NMR(100MHz，DMSO-d6)δ(ppm)：189.94，168.00，158.86，141.42，137.12，130.00，129.20，128.48(2C)，128.06，125.16，121.40，120.36，119.23，118.42(2C)，117.46，113.57，55.13，23.95。
Embodiment 29
Synthesizing of (4-(4-acetylamino phenyl)-1H-pyrroles-3-yl) (4-p-methoxy-phenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(4-p-methoxy-phenyl)-3-(4-acetylamino phenyl) acrylketone and TosMIC.
Product is yellow solid, yield 78.9%.
The experimental data of product is as follows:
1H?NMR(300MHz，DMSO-d6)δ(ppm)：11.52(s，1H，pyrrole-NH)，9.86(s，1H，PhNH-)，7.72(d，J＝9.0Hz，2H，ArH)，7.42(d，J＝9.0Hz，2H，ArH)，7.24(d，J＝9.0Hz，2H，ArH)，7.16(dd，J1＝3.0Hz，J2＝0.9Hz，1H，pyrrole?H)，7.01(t，J＝3.0Hz，1H，pyrrole?H)，6.97(d，J＝9.0Hz，2H，ArH)，3.80(s，3H，PhOCH3)，2.02(s，3H，-COCH3)；13C?NMR(100MHz，DMSO-d6)δ(PPm)：189.28，167.99，162.03，137.00，132.36，131.27(2C)，130.13，128.29(2C)，126.80，124.98，120.60，118.80，118.51(2C)，113.36(2C)，55.34，23.94。
Embodiment 30
Synthesizing of (4-(4-acetylamino phenyl)-1H-pyrroles-3-yl) (2-pyridyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(2-pyridyl)-3-(4-acetylamino phenyl) acrylketone and TosMIC.
Product is yellow solid, yield 50.9%.
The experimental data of product is as follows:
1H?NMR(400MHz，DMSO-d6)δ(ppm)：11.60(s，1H，pyrrole-NH)，9.88(s，1H，PhNH-)，8.65(m，1H，pyridine?H)，7.95(td，J1＝8.0Hz，J2＝2.0Hz，1H，pyridine?H)，7.83(dt，J1＝8.0Hz，J2＝2.0Hz，1H，pyridine?H)，7.74(dd，J1＝8.0Hz，J2＝2.0Hz，1H，pyrrole?H)，7.55(m，1H，pyridine?H)，7.50(d，J＝8.0Hz，2H，PhH)，7.35(d，J＝8.0Hz，2H，PhH)，6.97(t，J＝4.0Hz，1H，pyrrole?H)，2.05(s，3H，-COCH3)；13C?NMR(100MHz，DMSO-d6)δ(ppm)：187.41，168.01，156.82，148.24，137.19，137.07，130.55，130.33，128.82(2C)，125.76，125.67，122.99，119.05，118.98，118.32(2C)，23.95。
Embodiment 31
Synthesizing of (4-(4-acetylamino phenyl)-1H-pyrroles-3-yl) (3-pyridyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(3-pyridyl)-3-(4-acetylamino phenyl) acrylketone and TosMIC.
Product is yellow solid, yield 42.8%.
The experimental data of product is as follows:
1H?NMR(300MHz，DMSO-d6)δ(ppm)：11.71(s，1H，pyrrole-NH)，9.87(s，1H，PhNH-)，8.83(d，J＝3.0Hz，1H，pyridine?H)，8.70(dd，J1＝3.0Hz，J2＝0.9Hz，1H，pyridine?H)，8.05(dt，J1＝6.0Hz，J2＝3.0Hz，1H，pyridine?H)，7.48(m，1H，pyridine?H)，7.46(d，J＝9.0Hz，2H，ArH)，7.31(d，J＝9.0Hz，2H，ArH)，7.31-7.295(m，1H，pyrrole?H)，7.06(t，J＝3.0Hz，1H，pyrrole?H)，2.03(s，3H，-COCH3)。
Embodiment 32
Synthesizing of (4-(4-acetylamino phenyl)-1H-pyrroles-3-yl) (4-pyridyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(4-pyridyl)-3-(4-acetylamino phenyl) acrylketone and TosMIC.
Product is brown solid, yield 66.7%.
The experimental data of product is as follows:
1H?NMR(300MHz，DMSO-d6)δ(ppm)：11.75(s，1H，pyrrole-NH)，9.88(s，1H，PhNH-)，8.70(d，J＝6.0Hz，2H，pyridine?H)，7.57(d，J＝6.0Hz，2H，pyridine?H)，7.48(d，J＝6.0Hz，2H，ArH)，7.34(d，J＝6.0Hz，2H，ArH)，7.27(dd，J1＝3.0Hz，J2＝0.9Hz，1H，pyrrole?H)，7.05(t，J＝3.0Hz，1H，pyrrole?H)，2.04(s，3H，-COCH3)；13C?NMR(100MHz，DMSO-d6)δ(ppm)：188.83，168.06，149.89(2C)，146.88，137.37，129.70，129.60，128.75(2C)，122.29(2C)，119.95，119.66，118.37(2C)，23.96。
Embodiment 33
Synthesizing of (4-(4-acetylamino phenyl)-1H-pyrroles-3-yl) (2-thienyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(2-thienyl)-3-(4-acetylamino phenyl) acrylketone and TosMIC.
Product is yellow solid, yield 71.1%.
The experimental data of product is as follows:
1H?NMR(300MHz，DMSO-d6)δ(ppm)：11.62(s，1H，pyrrole-NH)，9.87(s，1H，PhNH-)，7.93(dd，J1＝3.0Hz，J2＝0.9Hz，1H，thiophenyl?H)，7.71(d，J＝3.0Hz，1H，thiophenyl?H)，7.50(m，1H，thiophenyl?H)，7.47(d，J＝6.0Hz，2H，ArH)，7.28(d，J＝6.0Hz，2H，ArH)，7.20(dd，J1＝3.0Hz，J2＝0.9Hz，1H，pyrrole?H)，7.04(t，J＝3.0Hz，1H，pyrrole?H)，2.03(s，3H，-COCH3)；13C?NMR(100MHz，DMSO-d6)δ(ppm)：181.87，168.03，145.63，137.14，133.19，132.93，129.89，128.31(2C)，128.18，126.64，124.80，120.19，119.17，118.58(2C)，23.95。
Embodiment 34
Synthesizing of (4-(4-acetylamino phenyl)-1H-pyrroles-3-yl) (phenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(phenyl)-3-(4-acetylamino phenyl) acrylketone and TosMIC.
Product is white solid, yield 65.3%.
The experimental data of product is as follows:
1H?NMR(400MHz，DMSO-d6)δ(ppm)：11.58(s，1H，pyrrole-NH)，9.87(s，1H，PhNH-)，7.73(d，J＝8.0Hz，2H，ArH)，7.56(t，d，J＝8.0Hz，1H，ArH)，7.47(d，J＝8.0Hz，2H，ArH)，7.45(d，J＝8.0Hz，2H，ArH)，7.30(d，J＝8.0Hz，2H，ArH)，7.19(t，J＝4.0Hz，1H，pyrrole?H)，7.04(t，J＝4.0Hz，1H，pyrrole?H)，2.04(s，3H，-COCH3)；13C?NMR(100MHz，DMSO-d6)δ(ppm)：190.33，167.99，140.07，137.13，131.41，130.02，128.88(2C)，128.48(2C)，128.08(2C)，128.00，125.19，120.45，119.20，118.46(2C)，23.94。
Embodiment 35
Synthesizing of (4-(4-acetylamino phenyl)-1H-pyrroles-3-yl) (1-naphthyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(1-naphthyl)-3-(4-acetylamino phenyl) acrylketone and TosMIC.
Product is yellow solid, yield 36.8%.
The experimental data of product is as follows:
1H?NMR(400MHz，DMSO-d6)δ(ppm)：11.58(s，1H，pyrrole-NH)，9.90(s，1H，PhNH-)，8/06-7.96(m，3H)，7.62(dd，J1＝8.0Hz，J2＝4.0Hz，1H)，7.57-7.43(m，7H)，7.02(t，J＝4.0Hz，1H，pyrrole?H)，9.69(t，J＝4.0Hz，1H，pyrrole?H)，2.05(s，3H，-COCH3)；13C?NMR(100MHz，DMSO-d6)δ(ppm)：191.43，168.02，138.93，137.32，133.14，130.14，129.97，129.88，129.69，128.81(2C)，128.21，126.63，126.10，126.00，125.33，125.17，124.66，122.29，119.88，118.31(2C)，23.96.
Embodiment 36
Synthesizing of (4-(4-acetylamino phenyl)-1H-pyrroles-3-yl) (4-xenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(4-xenyl)-3-(4-acetylamino phenyl) acrylketone and TosMIC.
Product is yellow solid, yield 64.2%.
The experimental data of product is as follows:
1H?NMR(400MHz，DMSO-d6)δ(ppm)：11.60(s，1H，pyrrole-NH)，9.87(s，1H，PhNH-)，7.83(d，J＝8.0Hz，2H，ArH)，7.77(d，J＝8.0Hz，2H，ArH)，7.74(d，J＝8.0Hz，2H，ArH)，7.51(t，J＝8.0Hz，2H，ArH)，7.46(t，J＝8.0Hz，2H，ArH)，7.42(m，1H，ArH)，7.32(d，J＝8.0Hz，2H，ArH)，7.27(t，J＝4.0Hz，1H，pyrrole?H)，7.06(t，J＝4.0Hz，1H，pyrrole?H)，2.03(s，3H，-COCH3)；13C?NMR(100MHz，DMSO-d6)δ(ppm)：189.84，167.99，142.98，139.19，138.85，137.15，130.04，129.69(2C)，129.02(2C)，128.49(2C)，128.05，127.90，126.84(2C)，126.35(2C)，125.19，120.50，119.20，118.49(2C)，23.94。
Embodiment 37
Synthesizing of (4-(3-p-methoxy-phenyl)-1H-pyrroles-3-yl) (2-fluorophenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(2-fluorophenyl)-3-(3-p-methoxy-phenyl) acrylketone and TosMIC.
Product is faint yellow solid, yield 65.4%.
The experimental data of product is as follows:
1H?NMR(400MHz，DMSO-d6)δ(ppm)：11.71(s，1H，NH)，7.51(m，2H，-CO-Ar-H)，7.26-7.15(m，4H，-CO-Ar-H+Ar-H)，7.08(t，J＝2Hz，1H，Ar-H)，7.04-7.02(m，2H，pyrrole-H+Ar-H)，6.78(m，1H，pyrrole-H)，3.74(s，3H，-OCH3)；13C?NMR(100MHz，DMSO-d6)δ(ppm)：186.49，160.04，158.66，157.58，136.13，131.88，131.79，129.80，129.73，129.69，129.65，129.50，128.51，124.98，124.11，124.08，121.62，121.01，120.40，115.95，115.73，114.25，111.50，54.83。
Embodiment 38
Synthesizing of (4-(3-p-methoxy-phenyl)-1H-pyrroles-3-yl) (4-fluorophenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(4-fluorophenyl)-3-(3-p-methoxy-phenyl) acrylketone and TosMIC.
Product is white solid, yield 72.5%.
The experimental data of product is as follows:
1H?NMR(400MHz，DMSO-d6)δ(ppm)：11.65(s，1H，NH)，7.80(dd，J1＝6.0Hz，J2＝8.4Hz，2H，-CO-Ar-H)，7.28-7.23(m，3H，-CO-Ar-H+Ar-H)，7.17(t，J＝8.0Hz，1H，Ar-H)，7.11(m，1H，pyrrole-H)，6.91-6.90(m，2H，Ar-H+pyrrole-H)，6.74(dd，J1＝2Hz，J2＝8.0Hz，1H，Ar-H)3.70(s，3H，-OCH3)；13C?NMR(100MHz，DMSO-d6)δ(ppm)：188.69，158.77，142.06，141.88，136.32，134.02，132.93，131.34，131.13，130.32，130.06，128.65，128.43，128.35，127.83，127.48，125.31，121.42，120.81，120.25，119.87，113.97，111.39，54.83。
Embodiment 39
Synthesizing of (4-(3-p-methoxy-phenyl)-1H-pyrroles-3-yl) (2-chloro-phenyl-) ketone
Preparation method is with embodiment 1, and raw material is 1-(2-chloro-phenyl-)-3-(3-p-methoxy-phenyl) acrylketone and TosMIC.
Product is faint yellow solid, yield 76.2%.
The experimental data of product is as follows:
1H?NMR(400MHz，DMSO-d6)δ(ppm)：11.71(s，1H，NH)，7.51-7.36(m，4H，-CO-Ar-H)，7.23(t，J＝8.0Hz，1H，Ar-H)，7.11-7.08(m，3H，Ar-H+pyrrole-H)，6.99(m，1H，pyrrole-H)，6.80(dd，J1＝2.4Hz，J2＝8.0Hz，2H，Ar-H)，3.76(s，3H，-OCH3)；13CNMR(100MHz，DMSO-d6)δ(ppm)：188.38，158.67，140.75，136.08，130.47，130.34，129.57，129.51，128.53，128.51，126.77，124.97，121.10，120.99，120.72，114.31，111.53，54.84。
Embodiment 40
Synthesizing of (4-(3-p-methoxy-phenyl)-1H-pyrroles-3-yl) (4-fluorophenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(4-chloro-phenyl-)-3-(3-p-methoxy-phenyl) acrylketone and TosMIC.
Product is faint yellow solid, yield 84.2%.
The experimental data of product is as follows:
1H?NMR(400MHz，DMSO-d6)δ(ppm)：11.70(s，1H，NH)，7.74(d，J＝8.4Hz，2H，-CO-Ar-H)，7.51(d，J＝8.4Hz，2H，-CO-Ar-H)，7.28(t，J＝2.4Hz，1H，Ar-H)，7.18(t，J＝8.0Hz，1H，Ar-H)，7.12(m，1H，pyrrole-H)，6.94-6.90(m，H，Ar-H+pyrrole-H)，6.76(dd，J1＝2.4Hz，J2＝8.0Hz，1H，Ar-H)，3.71(s，3H，-OCH3)；13C?NMR(100MHz，DMSO-d6)δ(ppm)：189.09，158.77，138.61，136.38，136.26，130.76，128.65，128.18，128.14，125.24，120.79，120.35，119.82，113.98，111.23，54.83。
Embodiment 41
Synthesizing of (4-(3-p-methoxy-phenyl)-1H-pyrroles-3-yl) (3-bromophenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(3-bromophenyl)-3-(3-p-methoxy-phenyl) acrylketone and TosMIC.
Product is faint yellow solid, yield 78.0%.
The experimental data of product is as follows:
1H?NMR(400MHz，DMSO-d6)δ(ppm)：11.71(s，1H，NH)，7.80-7.60(m，3H，-CO-Ar-H)，7.49(m，1H，-CO-Ar-H)，7.30(t，J＝2.5Hz，1H，pyrrole-H)，7.18(t，J＝7.6Hz，1H，Ar-H)，7.12(t，J＝7.6Hz，1H，Ar-H)，6.98-6.92(m，2H，Ar-H+pyrrole-H)，6.74(dd，J1＝2.5Hz，J2＝8.0Hz，1H，Ar-H)，3.71(s，3H，-OCH3)；13C?NMR(100MHz，DMSO-d6)δ(ppm)：188.98，165.25，162.77，158.77，136.45，131.68，131.59，128.65，127.75，125.21，120.75，120.50，119.67，115.13，114.91，113.93，111.18，54.81。
Embodiment 42
Synthesizing of (4-(3-p-methoxy-phenyl)-1H-pyrroles-3-yl) (4-bromophenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(4-bromophenyl)-3-(3-p-methoxy-phenyl) acrylketone and TosMIC.
Product is micro-yellow solid, yield 69.8%.
The experimental data of product is as follows:
1H?NMR(400MHz，DMSO-d6)δ(ppm)：11.70(s，1H，NH)，7.70-7.60(m，4H，-CO-Ar-H)，7.30(t，J＝2.3Hz，1H，pyrrole-H)，7.18(t，J＝8.0Hz，1H，Ar-H)，7.12(s，1H，Ar-H)，6.94-6.93(m，2H，Ar-H+pyrrole-H)，6.74(dd，J1＝2.2Hz，J2＝8.0Hz，1H，Ar-H)，3.71(s，3H，-OCH3)；13C?NMR(100MHz，DMSO-d6)δ(ppm)：189.22，158.77，138.96，136.37，131.13，130.93，128.66，128.20，125.26，125.24，120.79，120.30，119.84，113.99，111.23，54.83。
Embodiment 43
Synthesizing of (4-(3-p-methoxy-phenyl)-1H-pyrroles-3-yl) (3-p-methoxy-phenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(3-p-methoxy-phenyl)-3-(3-p-methoxy-phenyl) acrylketone and TosMIC.
Product is faint yellow solid, yield 79.4%.
The experimental data of product is as follows:
1H?NMR(400MHz，DMSO-d6)δ(ppm)：11.62(s，1H，NH)，7.38(t，J＝8.0Hz，1H，-CO-Ar-H)，7.31(d，J＝8.0Hz，1H，-CO-Ar-H)，7.25(m，1H，-CO-Ar-H)，7.21(s，1H，-CO-Ar-H)，7.17-7.10(m，3H，pyrrole-H+Ar-H)，6.98-6.90(m，2H，Ar-H+pyrrole-H)，6.74(dd，J1＝2.4Hz，J2＝8.0Hz，1H，Ar-H)，3.76(s，3H，-OCH3)，3.70(s，3H，-OCH3)；13C?NMR(100MHz，DMSO-d6)δ(ppm)：189.99，158.87，158.75，141.33，136.54，129.20，128.62，127.94，125.23，121.42，120.74，120.60，119.67，117.55，113.95，113.60，111.20，55.12，54.81。
Embodiment 44
Synthesizing of (4-(3-p-methoxy-phenyl)-1H-pyrroles-3-yl) (4-p-methoxy-phenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(4-p-methoxy-phenyl)-3-(3-p-methoxy-phenyl) acrylketone and TosMIC.
Product is faint yellow solid, yield 86.7%.
The experimental data of product is as follows:
1H?NMR(400MHz，DMSO-d6)δ(ppm)：11.59(s，1H，NH)，7.77(d，J＝8.8Hz，2H，-CO-Ar-H)，7.20(d，J＝1.6Hz，1H，pyrrole-H)，7.18(t，J＝8.0Hz，1H，Ar-H)，7.11(d，J＝1.6Hz，1H，pyrrole-H)，6.99(d，J＝8.8Hz，2H，-CO-Ar-H)，6.93-6.90(m，2H，Ar-H)，6.74(dd，J1＝1.6Hz，J2＝8.0Hz，1H，Ar-H)，3.82(s，3H，-OCH3)，3.69(s，3H，-OCH3)；13C?NMR(100MHz，DMSO-d6)δ(ppm)：189.34，162.09，158.80，136.64，132.30，131.28，128.68，126.66，125.01，120.82，120.57，119.26，113.77，113.37，110.98，55.36，54.79。
Embodiment 45
Synthesizing of (4-(3-p-methoxy-phenyl)-1H-pyrroles-3-yl) (3-pyridyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(3-pyridyl)-3-(3-p-methoxy-phenyl) acrylketone and TosMIC.
Product is yellowish solid, yield 90.8%.
The experimental data of product is as follows:
1H?NMR(400MHz，DMSO-d6)δ(ppm)：11.80(s，1H，NH)，8.70(d，J＝5.2Hz，2H，-CO-Ar-H)，7.59(d，J＝5.2Hz，2H，-CO-Ar-H)，7.33(s，1H，pyrrole-H)，7.25(t，J＝8.0Hz，1H，Ar-H)，7.12-7.09(m，3H，Ar-H+pyrrole-H)，6.83(dd，J1＝2Hz，J2＝8.0Hz，1H，Ar-H)，3.70(s，3H，-OCH3)；13C?NMR(100MHz，DMSO-d6)δ(ppm)：189.83，158.78，147.63，146.86，136.13，129.94，127.74，125.27，122.27，119.98，119.05，118.94，113.84，111.07，54.51。
Embodiment 46
Synthesizing of (4-(3-p-methoxy-phenyl)-1H-pyrroles-3-yl) (4-pyridyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(4-pyridyl)-3-(3-p-methoxy-phenyl) acrylketone and TosMIC.
Product is faint yellow solid, yield 86.5%.
The experimental data of product is as follows:
1H?NMR(400MHz，DMSO-d6)δ(ppm)：11.77(s，1H，NH)，8.81(d，J＝1.2Hz，1H，-CO-Ar-H)，8.72(dd，J1＝1.2Hz，J2＝4Hz，1H，-CO-Ar-H)，8.06(d，J＝8.0Hz，1H，-CO-Ar-H)，7.49(dd，J1＝4Hz，J2＝8.0Hz，1H，-CO-Ar-H)，7.33(t，J＝2Hz，1H，pyrrole-H)，7.26(t，J＝8.0Hz，1H，Ar-H)，7.11-7.08(m，3H，Ar-H+pyrrole-H)，6.85(dd，J1＝2.4Hz，J2＝8.0Hz，1H，Ar-H)，3.71(s，3H，-OCH3)；13C?NMR(100MHz，DMSO-d6)δ(ppm)：188.83，158.85，151.71，147.13，136.23，136.17，135.54，128.94，127.96，125.16，123.17，119.98，119.67，119.05，113.94，111.37，54.81。
Embodiment 47
Synthesizing of (4-(3-p-methoxy-phenyl)-1H-pyrroles-3-yl) (2-thienyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(2-thienyl)-3-(3-p-methoxy-phenyl) acrylketone and TosMIC.
Product is white solid, yield 70.8%.
The experimental data of product is as follows:
1H?NMR(400MHz，DMSO-d6)δ(ppm)：11.66(s，1H，NH)，7.92(d，J＝4Hz，1H，-CO-Ar-H)，7.71(d，J＝4Hz，1H，-CO-Ar-H)，7.51(t，J＝4Hz，1H，-CO-Ar-H)，7.20-7.15(m，2H，Ar-H)，7.13(s，1H，pyrrole-H)，6.96-6.92(m，2H，pyrrole-H+Ar-H)，6.77(dd，J1＝2.4Hz，J2＝8.0Hz，1H，Ar-H)，3.72(s，3H，-OCH3)；13C?NMR(100MHz，DMSO-d6)δ(ppm)：181.96，158.84，145.59，136.42，133.30，133.03，128.76，128.19，126.54，124.81，120.59，120.37，119.64，113.83，111.05，54.83。
Embodiment 48
Synthesizing of (4-(3-p-methoxy-phenyl)-1H-pyrroles-3-yl) (2-nitrophenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(2-nitrophenyl)-3-(3-p-methoxy-phenyl) acrylketone and TosMIC.
Product is faint yellow solid, yield 66.9%.
The experimental data of product is as follows:
1H?NMR(400MHz，DMSO-d6)δ(ppm)：11.72(s，1H，NH)，8.12(d，J＝7.6Hz，1H，-CO-Ar-H)，7.82(t，J＝7.6Hz，1H，-CO-Ar-H)，7.73(t，J＝7.6Hz，1H，-CO-Ar-H)，7.62(d，J＝7.6Hz，1H，-CO-Ar-H)，7.26(m，1H，Ar-H)，7.20(t，J＝8.0Hz，1H，Ar-H)，7.13(m，1H，pyrrole-H)，6.94-6.92(m，2H，Ar-H+pyrrole-H)，6.80(dd，J1＝2Hz，J2＝8.0Hz，1H，Ar-H)，3.73(s，3H，-OCH3)；13C?NMR(100MHz，DMSO-d6)δ(ppm)：188.13，158.77，146.79，137.14，136.43，133.96，130.51，129.08，129.01，127.84，125.16，124.07，120.60，120.48，119.65，113.94，111.16，54.79。
Embodiment 49
Synthesizing of (4-(3-p-methoxy-phenyl)-1H-pyrroles-3-yl) (phenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(phenyl)-3-(3-p-methoxy-phenyl) acrylketone and TosMIC.
Product is micro-yellow solid, yield 66.4%.
The experimental data of product is as follows:
1H?NMR(400MHz，DMSO-d6)δ(ppm)：8.61(s，1H，NH)，7.84(dt，J1＝0.8Hz，J2＝7.2Hz，2H，-CO-Ar-H)，7.51(tt，J1＝0.8Hz，J2＝7.2Hz，1H，-CO-Ar-H)，7.40(t，J＝7.2Hz，2H，-CO-Ar-H)，7.26(t，J＝2.8Hz，1H，pyrrole-H)，7.22(t，J＝7.6Hz，1H，Ar-H)，7.02(m，1H，Ar-H)，6.97(t，J＝2Hz，1H，Ar-H)，6.96(t，J＝2.8Hz，1H，pyrrole-H)，6.74(dd，J1＝2.4Hz，J2＝8.0Hz，1H，Ar-H)，3.77(s，3H，-OCH3)；13C?NMR(100MHz，DMSO-d6)δ(ppm)：190.36，158.75，139.95，136.53，131.49，128.92，128.62，128.09，127.94，125.24，120.75，120.62，119.68，113.95，111.17，54.81。
Embodiment 50
Synthesizing of (4-(3-p-methoxy-phenyl)-1H-pyrroles-3-yl) (1-naphthyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(1-naphthyl)-3-(3-p-methoxy-phenyl) acrylketone and TosMIC.
Product is white solid, yield 75.6%.
The experimental data of product is as follows:
1H?NMR(400MHz，DMSO-d6)δ(ppm)：11.67(s，1H，NH)，8.18(m，1H，-CO-Ar-H)，7.99(m，1H，-CO-Ar-H)，7.66-7.46(m，5H，-CO-Ar-H)，7.28(m，1H，pyrrole-H)，7.19(m，1H，Ar-H)，7.12(m，1H，pyrrole-H)，6.97(m，2H，Ar-H)，6.75(m，1H，Ar-H)，3.73(s，3H，-OCH3)；13C?NMR(100MHz，DMSO-d6)δ(ppm)：191.13，158.65，139.03，136.51，133.14，130.13，129.99，129.66，128.21，127.94，126.63，126.10，125.89，125.33，125.17，124.66，122.27，119.88，119.28，113.95，111.17，54.82。
Embodiment 51
Synthesizing of (4-(3-p-methoxy-phenyl)-1H-pyrroles-3-yl) (4-xenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(4-xenyl)-3-(3-p-methoxy-phenyl) acrylketone and TosMIC.
Product is yellowish solid, yield 83.4%.
The experimental data of product is as follows:
1H?NMR(400MHz，DMSO-d6)δ(ppm)：11.66(s，1H，NH)，7.85(d，J＝8.0Hz，2H，-CO-Ar-H)，7.77(d，J＝8.0Hz，2H，-CO-Ar-H)，7.743(d，J＝7.6Hz，2H，-CO-Ar-H)，7.53(t，J＝7.6Hz，2H，-CO-Ar-H)，7.43(t，J＝7.6Hz，1H，-CO-Ar-H)，7.29(m，1H，pyrrole-H)，7.20(m，1H，Ar-H)，7.13(m，1H，pyrrole-H)，6.98(m，2H，Ar-H)，6.76(m，1H，Ar-H)，3.72(s，3H，-OCH3)；13C?NMR(100MHz，DMSO-d6)δ(ppm)：189.87，158.79，143.04，139.17，138.75，136.56，129.73，129.03，128.66，128.07，127.89，126.84，126.36，125.23，120.75，120.66，119.73，113.97，111.15，54.82。
Embodiment 52
Synthesizing of (4-(3,4-Dimethoxyphenyl)-1H-pyrroles-3-yl) (2-fluorophenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(2-fluorophenyl)-3-(3,4-Dimethoxyphenyl) acrylketone and TosMIC.
Product is white solid, yield 53.5%.
The experimental data of product is as follows:
1H?NMR(400MHz，DMSO-d6)δ(ppm)：11.66(s，1H，NH)，7.52(m，2H，-CO-Ar-H)，7.25(m，2H，-CO-Ar-H)，7.13(s，1H，pyrrole-H)，7.08(d，J＝1.6Hz，1H，Ar-H)，7.03-6.99(m，2H，pyrrole-H+Ar-H)，6.85(d，J＝8.0Hz，1H，Ar-H)，3.75(s，3H，-OCH3)，3.73(s，3H，-OCH3)；13C?NMR(100MHz，DMSO-d6)δ(ppm)：186.52，159.98，157.52，147.85，147.32，131.77，131.69，129.80，129.69，127.55，125.10，124.09，121.53，120.74，119.80，115.92，115.70，113.08，111.39，55.52，55.31。
Embodiment 53
Synthesizing of (4-(3,4-Dimethoxyphenyl)-1H-pyrroles-3-yl) (4-fluorophenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(4-fluorophenyl)-3-(3,4-Dimethoxyphenyl) acrylketone and TosMIC.
Product is faint yellow solid, yield 69.3%.
The experimental data of product is as follows:
1H?NMR(400MHz，DMSO-d6)δ(ppm)：11.62(s，1H，NH)，7.80(dd，J1＝6.0Hz，J2＝8.4Hz，2H，-CO-Ar-H)，7.28-7.21(m，3H，-CO-Ar-H+pyrrole-H)，7.06(s，1H，pyrrole-H)，6.96(d，J＝1.6Hz，1H，Ar-H)，6.92(dd，J1＝1.6Hz，J2＝8.0Hz，1H，Ar-H)，6.85(d，J＝8.0Hz，1H，Ar-H)，3.73(s，3H，-OCH3)，3.68(s，3H，-OCH3)；13C?NMR(100MHz，DMSO-d6)δ(ppm)：189.08，165.16，162.69，147.99，147.13，136.60，131.64，131.55，127.92，127.69，125.29，120.45，120.41，119.06，115.07，114.85，112.82，111.53，55.50，55.32。
Embodiment 54
Synthesizing of (4-(3,4-Dimethoxyphenyl)-1H-pyrroles-3-yl) (2-chloro-phenyl-) ketone
Preparation method is with embodiment 1, and raw material is 1-(2-chloro-phenyl-)-3-(3,4-Dimethoxyphenyl) acrylketone and TosMIC.
Product is yellow solid, yield 52.8%.
The experimental data of product is as follows:
1H?NMR(400MHz，DMSO-d6)δ(ppm)：11.65(s，1H，NH)，7.52-7.42(m，3H，-CO-Ar-H)，7.39(t，J＝7.2Hz，1H，-CO-Ar-H)，7.15(d，J＝1.6Hz，1H，Ar-H)，7.08(dd，J1＝1.6Hz，J2＝8.0Hz，1H，Ar-H)，7.03(t，J＝2.4Hz，1H，pyrrole-H)，6.98(t，J＝2.4Hz，1H，pyrrole-H)，6.90(d，J＝8.0Hz，1H，Ar-H)，3.76(s，6H，-OCH3)；13C?NMR(100MHz，DMSO-d6)δ(ppm)：188.41，147.87，147.37，140.86，130.40，130.19，129.53，129.49，128.50，127.50，126.74，125.10，121.00，120.72，120.07，113.09，111.39，55.54，55.32。
Embodiment 55
Synthesizing of (4-(3,4-Dimethoxyphenyl)-1H-pyrroles-3-yl) (4-chloro-phenyl-) ketone
Preparation method is with embodiment 1, and raw material is 1-(4-chloro-phenyl-)-3-(3,4-Dimethoxyphenyl) acrylketone and TosMIC.
Product is yellow solid, yield 77.0%.
The experimental data of product is as follows:
1H?NMR(400MHz，DMSO-d6)δ(ppm)：11.66(s，1H，NH)，7.72(d，J＝8.0Hz，2H，-CO-Ar-H)，7.50(d，J＝8.0Hz，2H，-CO-Ar-H)，7.25(s，1H，pyrrole-H)，7.06(s，1H，pyrrole-H)，6.98(d，J＝1.6Hz，1H，Ar-H)，6.92(dd，J1＝1.6Hz，J2＝8.0Hz，1H，Ar-H)，6.85(d，J＝8.0Hz，1H，Ar-H)，3.73(s，3H，-OCH3)，3.69(s，3H，-OCH3)；13C?NMR(100MHz，DMSO-d6)δ(ppm)：189.19，147.99，147.18，138.80，136.11，130.73，128.13，128.06，127.85，125.32，120.51，120.26，119.21，112.87，111.54，55.53，55.34。
Embodiment 56
Synthesizing of (4-(3,4-Dimethoxyphenyl)-1H-pyrroles-3-yl) (3-bromophenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(3-bromophenyl)-3-(3,4-Dimethoxyphenyl) acrylketone and TosMIC.
Product is yellow solid, yield 73.7%.
The experimental data of product is as follows:
1H?NMR(400MHz，DMSO-d6)δ(ppm)：11.67(s，1H，NH)，7.77(s，1H，-CO-Ar-H)，7.73(d，J＝8.0Hz，1H，-CO-Ar-H)，7.69(d，J＝8.0Hz，1H，-CO-Ar-H)，7.40(t，J＝8.0Hz，1H，-CO-Ar-H)，7.29(t，J＝2.4Hz，1H，pyrrole-H)，7.06(t，J＝2.4Hz，1H，pyrrole-H)，6.95(d，J＝1.6Hz，1H，Ar-H)，6.92(dd，J1＝1.6Hz，J2＝8.0Hz，1H，Ar-H)，6.85(d，J＝8.0Hz，1H，Ar-H)，3.73(s，3H，-OCH3)，3.68(s，3H，-OCH3)；13CNMR(100MHz，DMSO-d6)δ(ppm)：188.79，147.99，147.19，142.23，133.89，131.34，130.27，128.23，127.79，125.39，121.37，120.51，120.19，119.26，112.90，111.55，55.52，55.31。
Embodiment 57
Synthesizing of (4-(3,4-Dimethoxyphenyl)-1H-pyrroles-3-yl) (4-bromophenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(4-bromophenyl)-3-(3,4-Dimethoxyphenyl) acrylketone and TosMIC.
Product is faint yellow solid, yield 62.8%.
The experimental data of product is as follows:
1H?NMR(400MHz，DMSO-d6)δ(ppm)：11.64(s，1H，NH)，7.72(s，4H，-CO-Ar-H)，7.25(t，J＝2.4Hz，1H，pyrrole-H)，7.06(t，J＝2.4Hz，1H，pyrrole-H)，6.98(d，J＝1.6Hz，1H，Ar-H)，6.94(dd，J1＝1.6Hz，J2＝8.0Hz，1H，Ar-H)，6.85(d，J＝8.0Hz，1H，Ar-H)，3.73(s，3H，-OCH3)，3.69(s，3H，-OCH3)；13C?NMR(100MHz，DMSO-d6)δ(ppm)：189.31，147.99，147.19，139.15，131.07，130.91，128.12，127.84，125.32，125.10，120.52，120.21，119.22，112.87，111.54，55.54，55.35。
Embodiment 58
Synthesizing of (4-(3,4-Dimethoxyphenyl)-1H-pyrroles-3-yl) (3-p-methoxy-phenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(3-p-methoxy-phenyl)-3-(3,4-Dimethoxyphenyl) acrylketone and TosMIC.
Product is yellow solid, yield 64.8%.
The experimental data of product is as follows:
1H?NMR(400MHz，DMSO-d6)δ(ppm)：11.59(s，1H，NH)，7.37(t，J＝8.0Hz，1H，-CO-Ar-H)，7.30(d，J＝8.0Hz，1H，-CO-Ar-H)，7.24(t，J＝2.4Hz，1H，pyrrole-H)，7.20(s，1H，-CO-Ar-H)，7.11(d，J＝8.0Hz，1H，-CO-Ar-H)，7.05(t，J＝2.4Hz，1H，pyrrole-H)，6.97(d，J＝1.6Hz，1H，Ar-H)，6.94(dd，J1＝1.6Hz，J2＝8.0Hz，1H，Ar-H)，6.85(d，J＝8.0Hz，1H，Ar-H)，3.76(s，3H，-OCH3)，3.73(s，3H，-OCH3)，3.68(s，3H，-OCH3)；13CNMR(100MHz，DMSO-d6)δ(ppm)：190.10，158.82，147.95，147.12，141.52，129.14，128.03，127.89，125.30，121.37，120.50，120.41，119.06，117.41，113.62，112.88，111.50，55.51，55.31，55.12。
Embodiment 59
Synthesizing of (4-(3,4-Dimethoxyphenyl)-1H-pyrroles-3-yl) (4-p-methoxy-phenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(4-p-methoxy-phenyl)-3-(3,4-Dimethoxyphenyl) acrylketone and TosMIC.
Product is yellow solid, yield 81.1%.
The experimental data of product is as follows:
1H?NMR(400MHz，DMSO-d6)δ(ppm)：11.55(s，1H，NH)，7.75(d，J＝8.4Hz，2H，-CO-Ar-H)，7.19(t，J-1.2Hz，1H，pyrrole-H)，7.05(t，J＝1.2Hz，1H，pyrrole-H)，6.99-6.95(m，3H，-CO-Ar-H+Ar-H)，6.91(dd，J1＝1.6Hz，J2＝8.0Hz，1H，Ar-H)，6.84(d，J＝8.0Hz，1H，Ar-H)，3.81(s，3H，-OCH3)，3.72(s，3H，-OCH3)，3.68(s，3H，-OCH3)；13C?NMR(100MHz，DMSO-d6)δ(ppm)：189.45，161.99，148.00，147.02，132.47，131.25，128.16，126.60，125.07，120.72，120.26，118.63，113.31，112.68，111.58，55.50，55.34，55.30。
Embodiment 60
Synthesizing of (4-(3,4-Dimethoxyphenyl)-1H-pyrroles-3-yl) (3-pyridyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(3-pyridyl)-3-(3,4-Dimethoxyphenyl) acrylketone and TosMIC.
Product is yellow solid, yield 81.9%.
The experimental data of product is as follows:
1H?NMR(400MHz，DMSO-d6)δ(ppm)：11.75(s，1H，NH)，8.69(d，J＝5.2Hz，2H，-CO-Ar-H)，7.57(d，J＝5.2Hz，2H，-CO-Ar-H)，7.29(t，J＝2.2Hz，1H，pyrrole-H)，7.08(t，J＝2.2Hz，1H，pyrrole-H)，7.05(d，J＝1.6Hz，1H，Ar-H)，6.98(dd，J1＝1.6Hz，J2＝8.0Hz，1H，Ar-H)，6.87(d，J＝8.0Hz，1H，Ar-H)，3.74(s，3H，-OCH3)，3.71(s，3H，-OCH3)；13C?NMR(100MHz，DMSO-d6)δ(ppm)：188.92，149.84，147.93，147.34，146.99，129.57，127.59，125.42，122.28，120.70，119.82，119.75，113.05，111.43，55.50，55.37。
Embodiment 61
Synthesizing of (4-(3,4-Dimethoxyphenyl)-1H-pyrroles-3-yl) (4-pyridyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(4-pyridyl)-3-(3,4-Dimethoxyphenyl) acrylketone and TosMIC.
Product is faint yellow solid, yield 87.3%.
The experimental data of product is as follows:
1H?NMR(400MHz，DMSO-d6)δ(ppm)：11.72(s，1H，NH)，8.82(d，J＝1.2Hz，1H，-CO-Ar-H)，8.69(dd，J1＝1.2Hz，J2＝4.8Hz，1H，-CO-Ar-H)，8.04(d，J＝8.0Hz，1H，-CO-Ar-H)，8.04(dd，J1＝4.8Hz，J2＝8.0Hz，1H，-CO-Ar-H)，7.32(t，J＝2.2Hz，1H，pyrrole-H)，7.08(t，J＝2.2Hz，1H，pyrrole-H)，6.99(d，J＝1.6Hz，1H，Ar-H)，6.95(dd，J1＝1.6Hz，J2＝8.0Hz，1H，Ar-H)，6.85(d，J＝8.0Hz，1H，Ar-H)，3.73(s，3H，-OCH3)，3.69(s，3H，-OCH3)；13C?NMR(100MHz，DMSO-d6)δ(ppm)：188.71，151.67，149.39，147.97，147.22，136.19，135.60，128.65，127.69，125.35，123.27，120.63，120.42，119.46，112.98，111.48，55.49，55.34。
Embodiment 62
Synthesizing of (4-(3,4-Dimethoxyphenyl)-1H-pyrroles-3-yl) (2-thienyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(2-thienyl)-3-(3,4-Dimethoxyphenyl) acrylketone and TosMIC.
Product is yellow solid, yield 78.9%.
The experimental data of product is as follows:
1H?NMR(400MHz，DMSO-d6)δ(ppm)：11.61(s，1H，NH)，7.91(d，J＝4.8Hz，1H，-CO-Ar-H)，7.68(d，J＝4Hz，1H，-CO-Ar-H)，7.49(t，J＝2.4Hz，1H，pyrrole-H)，7.19(dd，J1＝4Hz，J2＝4.8Hz1H，-CO-Ar-H)，7.05(t，J＝2.4Hz，1H，pyrrole-H)，7.00(d，J＝1.2Hz，1H，Ar-H)，6.92(dd，J1＝1.2Hz，J2＝8.0Hz，1H，Ar-H)，6.87(d，J＝8.0Hz，1H，Ar-H)，3.74(s，3H，-OCH3)，3.71(s，3H，-OCH3)；13C?NMR(100MHz，DMSO-d6)δ(PPm)：182.02，148.06，147.15，145.71，133.11，132.92，128.14，127.90，126.41，124.93，120.37，120.28，119.02，112.64，111.60，55.50，55.36。
Embodiment 63
Synthesizing of (4-(3,4-p-methoxy-phenyl)-1H-pyrroles-3-yl) (2-nitrophenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(2-nitrophenyl)-3-(3,4-Dimethoxyphenyl) acrylketone and TosMIC.
Product is faint yellow solid, yield 76.0%.
The experimental data of product is as follows:
1H?NMR(400MHz，DMSO-d6)δ(ppm)：11.67(s，1H，NH)，8.10(d，J＝7.6Hz，1H，-CO-Ar-H)，7.80(t，J＝7.6Hz，1H，-CO-Ar-H)，7.72(t，J＝7.6Hz，1H，-CO-Ar-H)，7.60(d，J＝7.6Hz，1H，-CO-Ar-H)，7.12(d，J＝1.6Hz，1H，Ar-H)，7.07(t，J＝2.4Hz，1H，pyrrole-H)，7.05-7.00(m，2H，pyrrole-H+Ar-H)，6.88(d，J＝8.0Hz，1H，Ar-H)，3.75(s，3H，-OCH3)，3.73(s，3H，-OCH3)；13C?NMR(100MHz，DMSO-d6)δ(ppm)：186.99，147.90，147.37，146.78，137.12，133.85，130.41，129.13，129.10，127.39，125.13，124.16，120.66，120.55，120.03，112.91，111.42，55.53，55.27。
Embodiment 64
Synthesizing of (4-(3,4-Dimethoxyphenyl)-1H-pyrroles-3-yl) (phenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(phenyl)-3-(3,4-Dimethoxyphenyl) acrylketone and TosMIC.
Product is faint yellow solid, yield 75.7%.
The experimental data of product is as follows:
1H?NMR(400MHz，DMSO-d6)δ(ppm)：11.59(s，1H，NH)，7.72(d，J＝7.2Hz，2H，-CO-Ar-H)，7.56(t，J＝7.2Hz，1H，-CO-Ar-H)，7.46(t，J＝7.2Hz，2H，-CO-Ar-H)，7.20(t，J＝2.4Hz，1H，pyrrole-H)，7.05(t，J＝2.4Hz，1H，pyrrole-H)，6.99(d，J＝1.6Hz，1H，Ar-H)，6.94(dd，J1＝1.6Hz，J2＝8.0Hz，1H，Ar-H)，6.85(d，J＝8.0Hz，1H，Ar-H)，3.73(s，3H，-OCH3)，3.68(s，3H，-OCH3)；13C?NMR(100MHz，DMSO-d6)δ(ppm)：190.46，147.96，147.11，140.14，131.35，128.89，128.03，128.01，127.89，125.30，120.52，120.43，119.07，112.87，111.50，55.50，55.32。
Embodiment 65
Synthesizing of (4-(3,4-Dimethoxyphenyl)-1H-pyrroles-3-yl) (1-naphthyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(1-naphthyl)-3-(3,4-Dimethoxyphenyl) acrylketone and TosMIC.
Product is faint yellow solid, yield 52.3%.
The experimental data of product is as follows:
1H?NMR(400MHz，DMSO-d6)δ(ppm)：11.63(s，1H，NH)，8.10(m，1H，-CO-Ar-H)，7.93(m，1H，-CO-Ar-H)，7.61-7.40(m，5H，-CO-Ar-H)，7.27(s，1H，pyrrole-H)，7.07(s，1H，pyrrole-H)，7.02(d，J＝2Hz，1H，Ar-H)，6.97(dd，J1＝2Hz，J2＝8.0Hz，1H，Ar-H)，6.89(d，J＝8.0Hz，1H，Ar-H)，3.73(s，3H，-OCH3)，3.70(s，3H，-OCH3)；13C?NMR(100MHz，DMSO-d6)δ(ppm)：190.99，147.90，147.37，139.02，133.15，130.11，129.81，129.70，128.50，127.39，126.63，126.13，125.80，125.30，125.14，124.59，122.14，120.03，112.91，119.57，111.42，55.53，55.27。
Embodiment 66
Synthesizing of (4-(3,4-Dimethoxyphenyl)-1H-pyrroles-3-yl) (4-xenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(4-xenyl)-3-(3,4-Dimethoxyphenyl) acrylketone and TosMIC.
Product is faint yellow solid, yield 64.6%.
The experimental data of product is as follows:
1H?NMR(400MHz，DMSO-d6)δ(ppm)：11.61(s，1H，NH)，7.83(d，J＝8.0Hz，2H，-CO-Ar-H)，7.76(t，J＝8.0Hz，4H，-CO-Ar-H)，7.53(t，J＝7.2Hz，2H，-CO-Ar-H)，7.44(t，J＝7.2Hz，1H，-CO-Ar-H)，7.28(t，J＝1.6Hz，1H，pyrrole-H)，7.08(t，J＝1.6Hz，1H，pyrrole-H)，7.02(d，J＝2Hz，1H，Ar-H)，6.96(dd，J1＝2Hz，J2＝8.0Hz，1H，Ar-H)，6.87(d，J＝8.0Hz，1H，Ar-H)，3.73(s，3H，-OCH3)，3.70(s，3H，-OCH3)；13C?NMR(100MHz，DMSO-d6)δ(ppm)：189.97，148.00，147.15，142.92，139.20，138.94，129.69，129.03，128.03，127.81，126.83，126.31，125.31，120.56，120.46，119.08，112.87，111.55，55.51，55.34。
Embodiment 67
3-nitro-4-(3,4,5-trimethoxyphenyl)-1H-pyrroles's is synthetic
Preparation method is with embodiment 1, and raw material is 1,2,3-trimethoxy-5-(2-nitroethylene base) benzene and TosMIC.
Product is brown solid, yield 48.6%.
The experimental data of product is as follows:
1H?NMR(400MHz，DMSO-d6)δ(ppm)：12.08(s，1H，pyrrole-NH)，7.95(t，J＝2.0Hz，1H，pyrrole?H)，7.01(t，J＝2.0Hz，1H，pyrrole?H)，6.70(s，2H，PhH)，3.77(s，6H，3’，5’-OCH3)，3.69(s，3H，4’-OCH3)；13C?NMR(100MHz，DMSO-d6)δ(ppm)：152.27(2C)，136.67，133.47，128.15，122.72，120.13，119.67，106.75(2C)，59.99，55.87(2C)。
Embodiment 68
3-cyano group-4-(3,4,5-trimethoxyphenyl)-1H-pyrroles's is synthetic
Preparation method is with embodiment 1, and raw material is 3-(3,4,5-trimethoxyphenyl) vinyl cyanide and TosMIC.
Product is yellow solid, yield 52.3%.
The experimental data of product is as follows:
1H?NMR(400MHz，CDCl3)δ(ppm)：8.94(s，1H，pyrrole-NH)，7.38(dd，J1＝2.8Hz，J2＝2.0Hz，1H，pyridine?H)，7.00(t，J＝2.8Hz，1H，pyrrole?H)，6.88(s，2H，PhH)，3.94(s，6H，3’，5’-OCH3)，3.90(s，3H，4’-OCH3)；13C?NMR(100MHz，DMSO-d6)δ(ppm)：153.03(2C)，136.38，128.81，128.35，125.29，117.63，117.58，103.45(2C)，89.26，60.04，55.81(2C)。
Embodiment 69
3-ethoxycarbonyl-4-(3,4,5-trimethoxyphenyl)-1H-pyrroles's is synthetic
Preparation method is with embodiment 1, and raw material is 3-(3,4,5-trimethoxyphenyl) ethyl propenoate and TosMIC.
Product is white solid, yield 61.3%.
The experimental data of product is as follows:
1H?NMR(400MHz，DMSO-d6)δ(ppm)：11.54(s，1H，pyrrole-NH)，7.46(t，J＝4.0Hz，1H，pyrrole?H)，6.98(t，J＝4.0Hz，1H，pyrrole?H)，6.77(s，2H，PhH)，4.14(dd，J1＝12.0Hz，J2＝8.0Hz，2H，-COOCH2-)，3.78(s，6H，3’，5’-OCH3)，3.67(s，3H，4'-OCH3)，1.20(t，J＝8.0Hz，3H，-CH3)；13C?NMR(100MHz，DMSO-d6)δ(ppm)：164.16，152.02(2C)，136.00，130.61，125.81，125.12，119.07，112.02，106.38(2C)，59.97，58.72，55.73(2C)，14.28。
Embodiment 70
3-ethanoyl-4-(3,4,5-trimethoxyphenyl)-1H-pyrroles's is synthetic
Preparation method is with embodiment 1, and raw material is 4-(3,4,5-trimethoxyphenyl)-3-butene-2-one and TosMIC.
Product is yellow solid, yield 87.7%.
The experimental data of product is as follows:
1H?NMR(400MHz，DMSO-d6)δ(ppm)：11.53(s，1H，pyrrole-NH)，7.67(dd，J1＝2.8Hz，J2＝2.0Hz，1H，pyridine?H)，6.98(t，J＝2.8Hz，1H，pyrrole?H)，6.76(s，2H，PhH)，3.76(s，6H，3’，5'-OCH3)，3.67(s，3H，4'-OCH3)，2.33(s，3H，-OCH3)；13C?NMR(100MHz，DMSO-d6)δ(ppm)：192.61，151.98(2C)，135.98，131.00，127.54，124.44，121.94，119.82，106.53(2C)，59.95，55.74(2C)，28.37。
Embodiment 71
Synthesizing of (4-(3,4,5-trimethoxyphenyl)-1H-pyrroles-3-yl) (2-fluorophenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(2-fluorophenyl)-3-(3,4,5-trimethoxyphenyl) acrylketone and TosMIC.
Product is white solid, yield 87.5%.
The experimental data of product is as follows:
1H?NMR(400MHz，DMSO-d6)δ(ppm)：11.70(s，1H，pyrrole-NH)，7.46(d，J＝8.0Hz，1H，ArH)，7.22(t，J＝8.0Hz，2H，ArH)，7.17(t，J＝4.0Hz，1H，pyrrole?H)，7.08(dd，J1＝4.0Hz，J2＝2.0Hz，1H，pyrrole?H)，6.75(s，2H，ArH)，3.74(s，6H，3’，5'-OCH3)，3.64(s，3H，4'-OCH3)；13C?NMR(100MHz，DMSO-d6)δ(ppm)：186.61，158.77(1C，JCF＝247.5Hz)，152.05(2C)，136.05，131.80(1C，JCF＝8.2Hz)，130.31，129.72，129.66(1C，JCF＝3.9Hz)，129.53，125.26，124.03(1C，JCF＝3.4Hz)，121.70，120.14，115.77(1C，JCF＝21.9Hz)，106.39(2C)，59.92，55.70(2C)。
Embodiment 72
Synthesizing of (4-(3,4,5-trimethoxyphenyl)-1H-pyrroles-3-yl) (4-fluorophenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(4-fluorophenyl)-3-(3,4,5-trimethoxyphenyl) acrylketone and TosMIC.
Product is faint yellow solid, yield 81.0%.
The experimental data of product is as follows:
1H?NMR(400MHz，DMSO-d6)δ(ppm)：11.66(s，1H，pyrrole-NH)，7.76(d，J＝4.0Hz，1H，ArH)，7.74(d，J＝4.0Hz，1H，ArH)，7.27(t，J＝4.0Hz，2H，pyrrole?H)，7.22(t，J＝8.0Hz，1H，ArH)，7.12(t，J＝4.0Hz，1H，pyrrole?H)，6.63(s，2H，ArH)，3.69(s，6H，3’，5'-OCH3)，3.62(s，3H，4'-OCH3)；13C?NMR(100MHz，DMSO-d6)δ(ppm)：189.18，163.91(1C，JCF＝249.1Hz)，152.18(2C)，136.59(1C，JCF＝2.9Hz)，135.89，131.58(2C，JCF＝9.0Hz)，130.70，127.67，125.41，120.62，119.42，114.89(2C，JCF＝21.7Hz)，106.15(2C)，59.95，55.70(2C)。
Embodiment 73
Synthesizing of (4-(3,4,5-trimethoxyphenyl)-1H-pyrroles-3-yl) (2-chloro-phenyl-) ketone
Preparation method is with embodiment 1, and raw material is 1-(2-chloro-phenyl-)-3-(3,4,5-trimethoxyphenyl) acrylketone and TosMIC.
Product is white solid, yield 89.9%.
The experimental data of product is as follows:
1H?NMR(400MHz，DMSO-d6)δ(ppm)：11.70(s，1H，pyrrole-NH)，7.50(d，J＝8.0Hz，1H，ArH)，7.44(t，J＝8.0Hz，2H，ArH)，7.37(m，1H，ArH)，7.10(t，J＝4.0Hz，1H，pyrrole?H)，7.03(dd，J1＝4.0Hz，J2＝2.0Hz，1H，pyrrole?H)，6.82(s，2H，ArH)，3.78(s，6H，3’，5’OCH3)，3.67(s，3H，4'-OCH3)；13C?NMR(100MHz，DMSO-d6)δ(ppm)：184.50，152.06(2C)，140.76，136.10，130.43，130.24，130.09，129.55，129.47，128.56，126.70，125.25，121.16，120.45，106.37(2C)，59.94，55.71(2C)。
Embodiment 74
Synthesizing of (4-(3,4,5-trimethoxyphenyl)-1H-pyrroles-3-yl) (4-chloro-phenyl-) ketone
Preparation method is with embodiment 1, and raw material is 1-(4-chloro-phenyl-)-3-(3,4,5-trimethoxyphenyl) acrylketone and TosMIC.
Product is white solid, yield 77.4%.
The experimental data of product is as follows:
1H?NMR(400MHz，DMSO-d6)δ(ppm)：11.69(s，1H，pyrrole-NH)，7.69(d，J＝8.0Hz，1H，ArH)，7.48(t，J＝8.0Hz，2H，ArH)，7.29(t，J＝4.0Hz，1H，pyrrole?H)，7.12(t，J＝4.0Hz，1H，pyrrole?H)，6.64(s，2H，ArH)，3.70(s，6H，3’，5’OCH3)，3.63(s，3H，4'-OCH3)；13C?NMR(100MHz，DMSO-d6)δ(ppm)：189.31，152.17(2C)，138.76，136.09，135.95，130.71(2C)，130.63，128.04(2C)，127.97，125.45，120.50，119.53，106.21(2C)，59.98，55.71(2C)。
Embodiment 75
Synthesizing of (4-(3,4,5-trimethoxyphenyl)-1H-pyrroles-3-yl) (3-bromophenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(3-bromophenyl)-3-(3,4,5-trimethoxyphenyl) acrylketone and TosMIC.
Product is yellow solid, yield 71.5%.
The experimental data of product is as follows:
1H?NMR(300MHz，DMSO-d6)δ(ppm)：11.71(s，1H，pyrrole-NH)，7.69(s，1H，ArH)，7.65(d，J＝9.0Hz，1H，ArH)，7.57(d，J＝9.0Hz，1H，ArH)，7.42(m，1H，ArH0，7.32(dd，J1＝3.0Hz，J2＝1.5Hz，1H，pyrrole?H)，7.10(t，J＝3.0Hz，1H，pyrrole?H)，6.60(s，2H，ArH)，3.68(s，6H，3’，5’-OCH3)，3.61(s，3H，4'-OCH3)；13C?NMR(100MHz，DMSO-d6)δ(ppm)：188.93，152.18(2C)，142.09，135.88，133.85，131.46，130.59，130.19，127.98，127.65，125.53，121.25，120.48，119.48，106.23(2C)，59.86，55.68(2C)。
Embodiment 76
Synthesizing of (4-(3,4,5-trimethoxyphenyl)-1H-pyrroles-3-yl) (4-bromophenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(4-bromophenyl)-3-(3,4,5-trimethoxyphenyl) acrylketone and TosMIC.
Product is faint yellow solid, yield 70.3%.
The experimental data of product is as follows:
1H?NMR(300MHz，DMSO-d6)δ(ppm)：11.69(s，1H，pyrrole-NH)，7.59(s，4H，ArH)，7.28(dd，J1＝3.0Hz，J2＝1.5Hz，1H，pyrrole?H)，7.11(t，J＝3.0Hz，1H，pyrrole?H)，6.63(s，2H，ArH)，3.69(s，6H，3’，5'-OCH3)，3.62(s，3H，4’-OCH3)；13C?NMR(100MHz，DMSO-d6)δ(ppm)：189.44，152.17(2C)，139.10，135.94，130.98(2C)，130.89(2C)，130.62，125.45，125.06，120.43，119.55，106.21(2C)，60.00，55.71(2C)。
Embodiment 77
Synthesizing of (4-(3,4,5-trimethoxyphenyl)-1H-pyrroles-3-yl) (4-aminomethyl phenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(4-aminomethyl phenyl)-3-(3,4,5-trimethoxyphenyl) acrylketone and TosMIC.
Product is white solid, yield 76.0%.
The experimental data of product is as follows:
1H?NMR(300MHz，DMSO-d6)δ(ppm)：11.59(s，1H，pyrrole-NH)，7.61(d，J＝6.0Hz，2H，ArH)，7.23(d，J＝6.0Hz，2H，ArH)，7.20-7.18(m，1H，pyrrole?H)，7.11(t，J＝3.0Hz，1H，pyrrole?H)，6.65(s，2H，ArH)，3.68(s，6H，3’，5’-OCH3)，3.62(s，3H，4’-OCH3)，2.33(s，3H，PhCH3)；13C?NMR(100MHz，DMSO-d6)δ(ppm)：190.31，152.17(2C)，141.46，137.38，135.85，130.85，129.12(2C)，128.54(2C)，127.38，125.31，120.83，119.27，106.06(2C)，59.96，55.69(2C)，20.97。
Embodiment 78
Synthesizing of (4-(3,4,5-trimethoxyphenyl)-1H-pyrroles-3-yl) (2,4-3,5-dimethylphenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(2,4-3,5-dimethylphenyl)-3-(3,4,5-trimethoxyphenyl) acrylketone and TosMIC.
Product is white solid, yield 69.1%.
The experimental data of product is as follows:
1H?NMR(300MHz，DMSO-d6)δ(ppm)：11.57(s，1H，pyrrole-NH)，7.22(d，J＝6.0Hz，1H，ArH)，7.06(t，J＝3.0Hz，1H，pyrrole?H)，7.03(s，1H，ArH)，6.97(t，J＝3.0Hz，1H，pyrrole?H)，6.99-6.94(m，1H，ArH)，6.75(s，2H，ArH)，3.73(s，6H，3’，5'-OCH3)，3.64(s，3H，4’-OCH3)，2.27(s，3H，PhCH3)，2.22(s，3H，PhCH3)；13CNMR(100MHz，DMSO-d6)δ(ppm)：192.25，152.06(2C)，138.62，138.49，135.97，135.17，131.03，130.66，129.09，128.02，125.39，125.22，122.15，119.93，106.27(2C)，59.96，55.69(2C)，20.77，19.36。
Embodiment 79
Synthesizing of (4-(3,4,5-trimethoxyphenyl)-1H-pyrroles-3-yl) (3-p-methoxy-phenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(3-p-methoxy-phenyl)-3-(3,4,5-trimethoxyphenyl) acrylketone and TosMIC.
Product is white solid, yield 79.1%.
The experimental data of product is as follows:
1H?NMR(300MHz，DMSO-d6)δ(ppm)：11.64(s，1H，pyrrole-NH)，7.32(t，J＝9.0Hz，1H，Ar?H)，7.28-7.22(m，2H，ArH)，7.15(dd，J1＝3.0Hz，J2＝1.5Hz，1H，pyrrole?H)，7.10(t，J＝3.0Hz，1H，pyrrole?H)，7.09-7.04(m，1H，ArH)，6.63(s，2H，ArH)，3.72(s，3H，-COPhOCH3)，3.68(s，6H，3’，5'-OCH3)，3.61(s，3H，4’-OCH3)；13C?NMR(100MHz，DMSO-d6)δ(ppm)：190.22，158.79，152.15(2C)，141.47，135.86，130.80，129.09，127.85，125.41，121.33，120.73，119.42，117.45，113.63，106.15(2C)，59.93，55.68(2C)，55.09。
Embodiment 80
Synthesizing of (4-(3,4,5-trimethoxyphenyl)-1H-pyrroles-3-yl) (4-p-methoxy-phenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(4-p-methoxy-phenyl)-3-(3,4,5-trimethoxyphenyl) acrylketone and TosMIC.
Product is white solid, yield 82.8%.
The experimental data of product is as follows:
1H?NMR(400MHz，DMSO-d6)δ(ppm)：11.57(s，1H，pyrrole-NH)，7.72(d，J＝8.0Hz，2H，ArH)，7.21(t，J＝4.0Hz，1H，pyrrole?H)，7.12(t，J＝4.0Hz，1H，pyrrole?H)，6.96(d，J＝8.0Hz，2H，ArH)，6.64(s，2H，ArH)，3.80(s，3H，-COPhOCH3)，3.68(s，6H，3’，5’-OCH3)，3.62(s，3H，4’-OCH3)；13C?NMR(100MHz，DMSO-d6)δ(ppm)：189.54，162.00，152.20(2C)，135.79，132.46，131.24(2C)，130.90，126.64，125.18，120.93，119.03，113.27(2C)，105.96(2C)，59.95，55.68(2C)，55.34。
Embodiment 81
Synthesizing of (4-(3,4,5-trimethoxyphenyl)-1H-pyrroles-3-yl) (2-pyridyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(2-pyridyl)-3-(3,4,5-trimethoxyphenyl) acrylketone and TosMIC.
Product is faint yellow solid, yield 68.3%.
The experimental data of product is as follows:
1H?NMR(400MHz，DMSO-d6)δ(ppm)：11.65(s，1H，pyrrole-NH)，8.62(m，1H，pyridine?H)，7.95(td，J1＝8.0Hz，J2＝2.0Hz，1H，pyridine?H)，7.80(td，J1＝8.0Hz，J2＝0.8Hz，1H，pyridine?H)，7.70(dd，J1＝4.0Hz，J2＝2.0Hz，1H，pyrrole?H)，7.54(m，1H，pyridine?H)，7.06(t，J＝4.0Hz，1H，pyrrole?H)，6.72(s，2H，PhH)，3.75(s，6H，3’，5’OCH3)，3.67(s，3H，4’-OCH3)；13C?NMR(100MHz，DMSO-d6)δ(ppm)：187.75，156.93，152.04(2C)，148.21，137.00，135.92，131.08，130.38，126.07，125.60，123.04，119.38，119.25，106.36(2C)，59.95，55.73(2C)。
Embodiment 82
Synthesizing of (4-(3,4,5-trimethoxyphenyl)-1H-pyrroles-3-yl) (3-pyridyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(3-pyridyl)-3-(3,4,5-trimethoxyphenyl) acrylketone and TosMIC.
Product is faint yellow solid, yield 50.0%.
The experimental data of product is as follows:
1H?NMR(400MHz，DMSO-d6)δ(ppm)：11.77(s，1H，pyrrole-NH)，8.80(s，1H，pyridine?H)，8.68(dd，J1＝8.0Hz，J2＝1.6Hz，1H，pyridine?H)，8.01(dt，J1＝8.0Hz，J2＝2.0Hz，1H，pyridine?H)，7.44(m，1H，pyridine?H)，7.36(dd，J1＝4.0Hz，J2＝1.6Hz，1H，pyrrole?H)，7.15(t，J＝4.0Hz，1H，pyrrole?H)，6.68(s，2H，PhH)，3.71(s，6H，3’，5’-OCH3)，3.64(s，3H，4’-OCH3)；13C?NMR(100MHz，DMSO-d6)δ(ppm)：188.78，152.18(2C)，151.65，149.36，136.16，135.96，135.58，130.46，128.61，125.46，123.21，120.59，119.84，106.30(2C)，59.94，55.73(2C)。
Embodiment 83
Synthesizing of (4-(3,4,5-trimethoxyphenyl)-1H-pyrroles-3-yl) (4-pyridyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(4-pyridyl)-3-(3,4,5-trimethoxyphenyl) acrylketone and TosMIC.
Product is faint yellow solid, yield 36.7%.
The experimental data of product is as follows:
1H?NMR(400MHz，DMSO-d6)δ(ppm)：11.80(s，1H，pyrrole-NH)，8.68(d，J＝8.0Hz，2H，pyridine?H)，7.56(d，J＝8.0Hz，2H，pyridine?H)，7.32(t，J＝4.0Hz，1H，pyrrole?H)，7.16(t，J＝4.0Hz，1H，pyrrole?H)，6.73(s，2H，PhH)，3.73(s，6H，3’，5’-OCH3)，3.65(s，3H，4’-OCH3)；13C?NMR(100MHz，DMSO-d6)δ(ppm)：189.00，152.14(2C)，149.80(2C)，146.93，136.10，130.37，129.56，125.54，122.28(2C)，120.21，119.91，106.37(2C)，59.96，55.76(2C)。
Embodiment 84
Synthesizing of (4-(3,4,5-trimethoxyphenyl)-1H-pyrroles-3-yl) (2-thienyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(2-thienyl)-3-(3,4,5-trimethoxyphenyl) acrylketone and TosMIC.
Product is white solid, yield 79.0%.
The experimental data of product is as follows:
1H?NMR(400MHz，DMSO-d6)δ(ppm)：11.66(s，1H，pyrrole-NH)，7.92(dd，J1＝4.0Hz，J2＝1.2Hz，1H，thiophene?H)，7.65(dd，J1＝4.0Hz，J2＝1.2Hz，1H，thiophene?H)，7.50(dd，J1＝4.0Hz，J2＝2.0Hz，1H，pyrrole?H)，7.18(dd，J1＝4.0Hz，J2＝1.2Hz，1H，thiophene?H)，7.14(t，J＝4.0Hz，1H，pyrrole?H)，6.70(s，2H，ArH)，3.73(s，6H，3’，5’-OCH3)，3.65(s，3H，4’-OCH3)；13C?NMR(100MHz，DMSO-d6)δ(PPm)：182.09，152.25(2C)，145.65，135.92，133.12，132.98，130.70，128.11，126.50，125.03，120.42，119.47，105.98(2C)，59.97，55.73(2C)。
Embodiment 85
Synthesizing of (4-(3,4,5-trimethoxyphenyl)-1H-pyrroles-3-yl) (1-naphthyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(1-naphthyl)-3-(3,4,5-trimethoxyphenyl) acrylketone and TosMIC.
Product is brown solid, yield 89.1%.
The experimental data of product is as follows:
1H?NMR(400MHz，DMSO-d6)δ(ppm)：11.51(s，1H，pyrrole-NH)，7.97(dd，J1＝8.0Hz，J2＝2.8Hz，1H，naphthalene?H)，7.91(d，J＝8.0Hz，1H，naphthalene?H)，7.51-7.46(m，3H，naphthalene?H)，7.40(t，J＝8.0Hz，1H，naphthalene?H)，7.14(t，J＝4.0Hz，1H，pyrrole?H)，7.03(t，J＝4.0Hz，1H，pyrrole?H)，6.57(s，2H，PhH)，3.68(s，6H，3’，5’-OCH3)，3.63(s，3H，4’-OCH3)；13C?NMR(100MHz，DMSO-d6)δ(ppm)：192.13，152.47(2C)，139.19，136.38，133.60，131.11，130.64，130.26，129.81，128.70，127.14，126.82，126.52，126.09，125.80，125.05，123.14，120.46，106.83(2C)，60.36，56.05(2C)。
Embodiment 86
Synthesizing of (4-(3,4,5-trimethoxyphenyl)-1H-pyrroles-3-yl) (4-xenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(4-xenyl)-3-(3,4,5-trimethoxyphenyl) acrylketone and TosMIC.
Product is faint yellow solid, yield 61.7%.
The experimental data of product is as follows:
1H?NMR(300MHz，DMSO-d6)δ(ppm)：11.66(s，1H，pyrrole-NH)，7.79(d，J＝6.0Hz，2H，ArH)，7.72(d，J＝6.0Hz，2H，ArH)，7.70(d，J＝6.0Hz，2H，ArH)，7.48(t，J＝6.0Hz，2H，ArH)，7.40(t，J＝6.0Hz，1H，ArH)，7.30(t，J＝6.0Hz，1H，pyrrole?H)，7.13(t，J＝6.0Hz，1H，pyrrole?H)，6.67(s，2H，ArH)，3.69(s，6H，3’，5’-OCH3)，3.59(s，3H，4’-OCH3)；13C?NMR(100MHz，DMSO-d6)δ(ppm)：190.06，152.19(2C)，142.94，139.20，138.89，135.91，130.79，129.70(2C)，129.01(2C)，128.04，127.80，126.81(2C)，126.25(2C)，125.43，120.76，119.47，106.16(2C)，59.94，55.72(2C)。
Embodiment 87
Synthesizing of (4-(2-naphthyl)-1H-pyrroles-3-yl) (2-fluorophenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(2-fluorophenyl)-3-(2-naphthyl) acrylketone and TosMIC.
Product is brown solid, yield 61.6%.
The experimental data of product is as follows:
1H?NMR(400MHz，DMSO-d6)δ(ppm)：11.81(s，1H，pyrrole-NH)，7.89(dd，J1＝8.0Hz，J2＝2.0Hz，1H，naphthalene?H)，7.82(d，J＝12.0Hz，2H，naphthalene?H)，7.45(t，J＝8.0Hz，2H)，7.43-7.35(m，4H)，7.33(t，J＝4.0Hz，1H，pyrrole?H)，7.14(dd，J1＝4.0Hz，J2＝2.0Hz，1H)，7.12(d，J＝8.0Hz，1H)，7.00(t，J＝4.0Hz，1H，pyrrole?H)；13C?NMR(100MHz，DMSO-d6)δ(ppm)：186.04，158.67JCF＝247.7Hz，133.53，132.95，132.35，131.66JCF＝8.1Hz，129.42JCF＝3.4Hz，129.06JCF＝15.9Hz，128.22，127.78，127.20，126.68，125.96，125.44，125.27，125.08，123.86JCF＝3.4Hz，123.68，122.52，120.92，115.63JCF＝21.7Hz。
Embodiment 88
Synthesizing of (4-(2-naphthyl)-1H-pyrroles-3-yl) (2-chloro-phenyl-) ketone
Preparation method is with embodiment 1, and raw material is 1-(2-chloro-phenyl-)-3-(2-naphthyl) acrylketone and TosMIC.
Product is yellow solid, yield 75.3%.
The experimental data of product is as follows:
1H?NMR(400MHz，DMSO-d6)δ(ppm)：11.80(s，1H，pyrrole-NH)，7.90(d，J＝8.0Hz，1H，naphthalene?H)，7.86(d，J＝8.0Hz，1H，naphthalene?H)，7.82(d，J＝8.0Hz，1H，naphthalene?H)，7.48-7.43(m，2H)，7.50-7.30(m，5H)，7.27(m，1H)，7.17(dd，J1＝4.0Hz，J2＝2.0Hz，1H，pyrrole?H)，6.99(t，J＝4.0Hz，1H，pyrrole?H)；13C?NMR(100MHz，DMSO-d6)δ(ppm)：187.82，140.22，133.51，132.93，132.38，130.37，129.48，129.37，128.82，128.43，127.74，127.19，126.74，126.55，126.30，125.40，125.31，125.06，123.12，122.49，121.25。
Embodiment 89
Synthesizing of (4-(2-naphthyl)-1H-pyrroles-3-yl) (4-chloro-phenyl-) ketone
Preparation method is with embodiment 1, and raw material is 1-(4-chloro-phenyl-)-3-(2-naphthyl) acrylketone and TosMIC.
Product is yellow solid, yield 58.1%.
The experimental data of product is as follows:
1H?NMR(400MHz，DMSO-d6)δ(ppm)：11.81(s，1H，pyrrole-NH)，7.88(dd，J1＝8.0Hz，J2＝2.0Hz，1H，naphthalene?H)，7.80(m，2H，naphthalerne?H)，7.66(d，J＝8.0Hz，2H，PhH)，7.46-7.42(m，2H，naphthalene?H)，7.43(d，J＝8.0Hz，2H，PhH)，7.41(t，J＝4.0Hz，1H，pyfrole?H)，7.35(dd，J1＝8.0Hz，J2＝2.0Hz，2H，naphthalene?H)，7.04(t，J＝4.0Hz，1H，pyrrole?H)；13C?NMR(100MHz，DMSO-d6)δ(ppm)：188.39，138.40，135.96，133.83，133.04，132.24，130.34(2C)，128.03(2C)，127.83，127.25，127.20，126.50，125.79，125.47，125.27，125.19，122.97，122.29，120.64。
Embodiment 90
Synthesizing of (4-(2-naphthyl)-1H-pyrroles-3-yl) (2,4-3,5-dimethylphenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(2,4-3,5-dimethylphenyl)-3-(2-naphthyl) acrylketone and TosMIC.
Product is brown solid, yield 62.4%.
The experimental data of product is as follows:
1H?NMR(400MHz，DMSO-d6)δ(ppm)：11.68(s，1H，pyrrole-NH)，7.89(dd，J1＝8.0Hz，J2＝2.0Hz，1H，naphthalene?H)，7.82(d，J＝8.0Hz，2H)，7.470-7.41(m，2H)，7.39-7.34(m，2H)，7.26(d，J＝8.0Hz，2H)，7.12(dd，J1＝4.0Hz，J2＝2.0Hz，1H，pyrrole?H)，6.99-6.93(m，3H，1pyrrole?H+2ArH)，2.26(s，3H，phCH3)，2.15(s，3H，phCH3)；13C?NMR(100MHz，DMSO-d6)δ(ppm)：191.46，138.52，137.93，135.11，134.05，132.99，132.43，131.00，127.91，127.80，127.76，127.06，126.48，126.12，125.32，125.29，125.24，125.12，124.09，122.61，120.74，20.75，19.25。
Embodiment 91
3-cyano group-4-(2-pyridyl)-1H-pyrroles's is synthetic
Preparation method is with embodiment 1, and raw material is 3-(2-pyridyl) vinyl cyanide and TosMIC.
Product is brown solid, yield 74.4%.
The experimental data of product is as follows:
1H?NMR(400MHz，DMSO-d6)δ(ppm)：12.01(s，1H，pyrrole-NH)，8.56(s，1H，pyridine?H)，7.80(t，J＝8.0Hz，1H，pyridine?H)，7.75(m，2H，pyridine?H)，7.60(t，J＝4.0Hz，1H，pyrrole?H)，7.22(t，J＝4.0Hz，1H，pyrrole?H)；13C?NMR(100MHz，DMSO-d6)δ(ppm)：191.91，149.23，136.75，129.26，124.93，121.41，119.67，119.30，117.27，89.81。
Embodiment 92
3-ethoxycarbonyl-4-(2-pyridyl)-1H-pyrroles's is synthetic
Preparation method is with embodiment 1, and raw material is 3-(2-pyridyl) ethyl propenoate and TosMIC.
Product is brown solid, yield 53.8%.
The experimental data of product is as follows:
1H?NMR(400MHz，DMSO-d6)δ(ppm)：11.62(s，1H，pyrrole-NH)，8.50(m，1H，pyridine?H)，7.77(dt，J1＝8.0Hz，J2＝2.0Hz，1H，pyridine?H)，7.70(dt，J1＝8.0Hz，J2＝2.0Hz，1H，pyridine?H)，7.47(dd，J1＝4.0Hz，J2＝2.0Hz，1H，pyrrole?H)，7.22(t，J＝4.0Hz，1H，pyrrole?H)，7.18(m，1H，pyridine?H)，4.15(dd，J1＝12.0Hz，J2＝4.0Hz，2H，-COOCH2-)，1.20(t，J＝8.0Hz，3H，-CH3)；13C?NMR(100MHz，DMSO-d6)δ(ppm)：164.29，153.49，148.46，135.60，125.96，124.66，123.24，121.19，120.85，112.39，58.98，14.17。
Embodiment 93
Synthesizing of (4-(2-pyridyl)-1H-pyrroles-3-yl) (4-aminomethyl phenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(4-aminomethyl phenyl)-3-(2-pyridyl) acrylketone and TosMIC.
Product is faint yellow solid, yield 71.3%.
The experimental data of product is as follows:
1H?NMR(400MHz，DMSO-d6)δ(ppm)：11.64(s，1H，pyrrole-NH)，8.37(m，1H，pyridine?H)，7.67(d，J＝8.0Hz，2H，PhH)，7.63(td，J1＝8.0Hz，J2＝4.0Hz，1H，pyridine?H)，7.52(dt，J1＝8.0Hz，J2＝0.8Hz，1H，pyridine?H)，7.36(t，J＝4.0Hz，1H，pyrrole?H)，7.26(d，J＝8.0Hz，2H，PhH)，7.20(dd，J1＝4.0Hz，J2＝2.0Hz，1H，pyrrole?H)，7.09(ddd，J1＝7.2Hz，J2＝5.2Hz，J1＝0.8Hz，1H，pyridine?H)，2.36(s，3H，phCH3)；13C?NMR(100MHz，DMSO-d6)δ(ppm)：190.47，153.72，148.56，141.73，137.02，135.66，129.16(2C)，128.63(2C)，126.63，125.09，122.18，121.34，121.04，120.47，21.0l。
Embodiment 94
Synthesizing of (4-(2-pyridyl)-1H-pyrroles-3-yl) (2,4-3,5-dimethylphenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(2,4-3,5-dimethylphenyl)-3-(2-pyridyl) acrylketone and TosMIC.
Product is faint yellow solid, yield 55.9%.
The experimental data of product is as follows:
1H?NMR(400MHz，DMSO-d6)δ(ppm)：11.64(s，1H，pyrrole-NH)，8.43(dd，J1＝4.0Hz，J2＝1.6Hz，1H，pyridine?H)，7.74(d，J＝8.0Hz，1H)，7.66(td，J1＝8.0Hz，J2＝1.6Hz，1H，pyridine?H)，7.32(t，J＝4.0Hz，1H，pyrrole?H)，7.26(d，J＝8.0Hz，1H)，7.14dd，J1＝8.0Hz，J2＝4.0Hz，1H，pyrrole?H)，7.07(s，1H，PhH)，7.02-6.97(m，2H)，2.30(s，3H，phCH3)，2.28(s，3H，phCH3)；13C?NMR(100MHz，DMSO-d6)δ(ppm)：192.59，153.61，148.48，138.94，138.26，135.69，135.54，131.17，128.80，128.29，125.40，124.93，122.81，122.69，121.90，120.68，20.79，19.48
Embodiment 95
Synthesizing of (4-(2-pyridyl)-1H-pyrroles-3-yl) (2-thienyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(2-thienyl)-3-(2-pyridyl) acrylketone and TosMIC.
Product is yellow solid, yield 62.4%.
The experimental data of product is as follows:
1H?NMR(400MHz，DMSO-d6)δ(ppm)：11.71(s，1H，pyrrole-NH)，8.42(m，1H，pyridine?H)，7.94(dd，J1＝4.0Hz，J2＝2.0Hz，1H)，7.70-7.62(m，2H)，7.52-7.46(m，2H)，7.36(t，J＝4.0Hz，1H，pyrrole?H)，7.18(dd，J1＝4.0Hz，J2＝2.0Hz，1H，pyrrole?H)，7.12(m，1H)；13C?NMR(100MHz，DMSO-d6)δ(ppm)：182.38，153.58，148.65，145.57，135.85，133.47，133.16，128.18，126.12，124.78，122.09，121.30，120.91，120.61。
Embodiment 96
Synthesizing of (4-(2-pyridyl)-1H-pyrroles-3-yl) (phenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(phenyl)-3-(2-pyridyl) acrylketone and TosMIC.
Product is faint yellow solid, yield 64.6%.
The experimental data of product is as follows:
1H?NMR(400MHz，DMSO-d6)δ(ppm)：11.70(s，1H，pyrrole-NH)，8.35(dd，J1＝4.0Hz，J2＝1.6Hz，1H，pyridine?H)，7.75(d，J＝8.0Hz，2H，PhH)，7.63(td，J1＝8.0Hz，J2＝1.6Hz，1H，pyridine?H)，7.55(m，2H，PhH)，7.44(t，J＝8.0Hz，2H，pyridine?H)，7.37(t，J＝4.0Hz，1H，pyrrole?H)，7.23(t，J＝4.0Hz，1H，pyrrole?H)，7.09(ddd，J1＝7.2Hz，J2＝5.2Hz，J3＝0.8Hz，1H，pyridine?H)；13C?NMR(100MHz，DMSO-d6)δ(ppm)：190.80，153.66，148.53，139.72，135.66，131.58，128.93(2C)，128.05(2C)，127.04，125.18，122.27，121.25，121.14，120.51。
Embodiment 97
Synthesizing of (4-(2-pyridyl)-1H-pyrroles-3-yl) (1-naphthyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(1-naphthyl)-3-(2-pyridyl) acrylketone and TosMIC.
Product is brown solid, yield 54.3%.
The experimental data of product is as follows:
1H?NMR(400MHz，DMSO-d6)δ(ppm)：11.70(s，1H，pyrrole-NH)，8.36(dd，J1＝4.0Hz，J2＝1.6Hz，1H)，8.13(d，J＝8.0Hz，1H)，8.03(d，J＝8.0Hz，2H)，8.00-7.96(m，1H)，7.83(d，J＝8.0Hz，1H)，7.67(dd，J1＝8.0Hz，J2＝4.0Hz，1H)，7.64(d，J＝8.0Hz，1H)，7.57-7.48(m，3H)，7.36(t，J＝4.0Hz，1H，pyrrole?H)，7.12(dd，J1＝8.0Hz，J2＝4.0Hz，1H)，7.06(t，J＝4.0Hz，1H，pyrrole?H)；13C?NMR(100MHz，DMSO-d6)δ(ppm)：191.97，153.56，148.45，138.71，135.59，133.15，130.25，130.01，129.49，128.18，126.70，126.43，126.10，125.46，125.21，124.55，123.04，122.89，122.06，120.77。
Two, 3, the cell inhibitory effect of 4-disubstituted pyrroles compound is active
1. reagent and material
Cell strain used is totally 16 kinds of tumour cells, comprise people's gastric adenocarcinoma cells (SGC-7901), gastric carcinoma cells (MGC80-3), National People's Congress's cell lung cancer cell (NCI-H460), Human Prostate Cancer Cells (DU145), human breast cancer cell (MCF-7), human cervical carcinoma cell (Hela), people's malignant melanoma cell (A375), the chronic marrow of people source leukemia (K562), human colon cancer cell (HCT-116), people ties Rectal Adenocarcinoma Cells (HCT-15), human liver cancer cell (Hep G2), human osteosarcoma cell (MG-63), human lung carcinoma cell (A549), mouse leukemia cell (L1210), mouse colonic cell (CT-26) and Chinese hamster ovary cancer cells (CHO), and two kinds of normal cell strain human umbilical vein endothelial cells (HUVEC) and mouse embryo cell (NIH/3T3).
Agents useful for same mainly comprises RPMI-1640 substratum (HyClone), DMEM (high sugar) substratum (HyClone), foetal calf serum (HyClone, South America blood relationship), nonessential amino acid (HyClone, Non-Essential Amino Acids Solution), penicillin-Streptomycin sulphate (dual anti-) solution (HyClone), 0.25%trypsin-EDTA pancreatin solution (Gibco), tetrazolium bromide (Sigma), biology DMSO, PBS damping fluid (HyClone), sodium lauryl sulphate (Chemical Reagent Co., Ltd., Sinopharm Group, SDS), isopropylcarbinol (Chemical Reagent Co., Ltd., Sinopharm Group), concentrated hydrochloric acid (Chemical Reagent Co., Ltd., Sinopharm Group), positive control taxol (Sigma) and 5 FU 5 fluorouracil (Sigma).
Consumptive material used mainly comprises aseptic dropper, aseptic pin type filter (Millex), Tissue Culture Dish (Corning) and 96 orifice plates (Corning).
Instrument mainly comprises sterile purification worktable (Shanghai new talent medicine equipment is prepared company limited), CO2gas incubator (Thermo Forma Series II), enzyme-linked immunosorbent assay instrument (Thermo MK3), inverted microscope (Olympus IX71, electronic balance (Metter ToledoAL204) and whizzer (flying pigeon TDL80-23).
2. the configuration of sample and reagent
By 3,4-disubstituted pyrroles compound and positive control (taxol and 5 FU 5 fluorouracil) are dissolved in biology DMSO, the stoste that is configured to 1.0mg/mL is stand-by, before experiment, with serum free medium, is diluted to the sample dope that concentration is respectively 1000mg/mL, 500mg/mL, 200mg/mL, 100mg/mL, 10mg/mL and 1mg/mL; Negative control solution is the culture medium solution that only contains equivalent DMSO.
The preparation of MTT solution: 0.5g MTT solid is dissolved in 100mL PBS solution, and final concentration is 5mg/mL, stand-by after sterile filtration, lucifuge-20 ℃ preservation.
The preparation of three liquid: 10g SDS, 5mL isopropylcarbinol and 0.1mL concentrated hydrochloric acid (36.5%) are dissolved in appropriate distilled water to be mixed with three liquid of 100mL stand-by.
3. mtt assay is measured IC50 value
By frozen cell recovery to be measured, with the substratum that contains 10% foetal calf serum and 1% dual anti-solution, carry out cell cultures, culture dish is placed in 37 ℃ of constant temperature, containing the incubator of 5% carbonic acid gas, the cultivation of cell, changes liquid and goes down to posterity and all according to standard operation, carry out.
The take the logarithm cell of phase growth, through trysinization, blow and beat into after individual cells, being mixed with cell concn is 5 * 10
4the cell suspension of individual/mL, be inoculated in 96 orifice plates, every hole 90 μ L, 96 orifice plates are placed in to cell culture incubator to be cultivated after 24h, add containing different concns 3, the sample solution of 4-disubstituted pyrroles compound, the sample solution that contains different concns positive control taxol and each 10 μ L of negative control solution, make medicine and positive control concentration be respectively 100mg/mL, 50mg/mL, 20mg/mL, 10mg/mL, 1mg/mL and 0.1mg/mL, each concentration arranges 4 multiple holes, continues to cultivate 24h in cell culture incubator.Finish the MTT solution that after cultivating, every hole adds 20 μ L, continue to cultivate 6h.
Finish after MTT cultivation, concerning attached cell, aftertreatment is: abandon the supernatant liquor in 96 orifice plates, the DMSO that adds 100 μ L, after first a ceremonial jade-ladle, used in libation is fully dissolved, enzyme-linked immunosorbent assay instrument detects the OD value under 570nm, make accordingly the typical curve of compound concentration and inhibiting rate, use nonlinear regression analysis to calculate correspondingly IC50 value.Concerning suspension cell, aftertreatment is: directly to three liquid that add 100 μ L in 96 orifice plates, cultivate 12 hours, enzyme-linked immunosorbent assay instrument detects the OD value under 570nm, makes accordingly the typical curve of compound concentration and inhibiting rate, uses nonlinear regression analysis to calculate corresponding IC50 value.
Compound is as shown in table 2 compared with the IC50 value of Sensitive Tumor Cells (μ mol/L) to normal cell and part.
Table 2
Compound and the IC50 value thereof with other sensitive cells strains are as shown in table 3:
Table 3
Note: cell inhibitory effect activity experiment all repeats 3 times;
> 100: illustrate that compound is very little to this cell strain lethal effect;
----: illustrate compound to this cell strain without lethal effect.
In sum, the present invention adopts Van Leusen pyrroles synthesis method, has synthesized 97 3,4-disubstituted pyrroles compound, and reaction has that the time is short, productive rate is high and the advantage such as side reaction is few.Data presentation through mtt assay test compounds cell inhibitory effect activity, 3,4-disubstituted pyrroles compound has excellent cytotoxicity to kinds of tumor cells, and the activity of chemical compound lot is better than 5 FU 5 fluorouracil, even can match in excellence or beauty with taxol, or the active taxol that surpasses.With the better positive drug taxol contrast of activity, advantage of the present invention is as follows:
Embodiment 4,38,40,51,53,55-59,62 and 75 product to the cell inhibitory effect of MGC80-3 active with taxol in the same order of magnitude, wherein embodiment 55,57 and 59 activity are greater than taxol;
Embodiment 55,57,59 and 62 product are greater than taxol to the cell inhibitory effect activity of DU145;
Embodiment 13,15,53,55,56,57,59,62 and 64 product to the cell inhibitory effect of Hep G2 active with taxol in the same order of magnitude, wherein embodiment 13,15,55,56,57,59,62 and 64 activity are greater than taxol;
The product of embodiment 42 to the cell inhibitory effect of MCF-7 active with taxol in the same order of magnitude;
Embodiment 2,38,42,49,51,55,57-59,62,64,66,75 and 76 product to the cell inhibitory effect of CHO active with taxol in the same order of magnitude, wherein embodiment 57,58,59 and 66 activity are greater than taxol;
Embodiment 42,44,53,55-57,59,62,64 and 66 product are greater than taxol to the cell inhibitory effect activity of CT-26.
Meanwhile, these compounds, on almost not impact of normal cell, can infer that 3,4-disubstituted pyrroles compound is being full of prospect aspect antitumor utilization in the future thus.
Claims (8)
1. one kind 3,4-disubstituted pyrroles compound, is characterized in that, this compound has the structure shown in following general formula:
Wherein, R
1=3,4-F
2during Ph, R
2=2-FPhCO, 4-FPhCO, 2-ClPhCO, 4-ClPhCO, 3-BrPhCO, 4-BrPhCO, 3-CH
3oPhCO, 4-CH
3oPhCO, 3-PyridylCO, 4-PyridylCO, 2-ThienylCO, 2-NO
2phCO, PhCO, 1-naphtholCO or 4-biphenylCO;
R
1during=4-CH3CONHPh, R
2=NO
2, CN, COOEt, COCH
3, 2-FPhCO, 4-FPhCO, 2-ClPhCO, 4-ClPhCO, 3-BrPhCO, 4-BrPhCO, 4-CH
3phCO, 2,4-(CH
3)
2phCO, 3-CH
3oPhCO, 4-CH
3oPhCO, 2-pyridylCO, 3-pyridylCO, 4-pyridylCO, 2-thienylCO, PhCO, 1-naphtholCO or 4-biphenylCO;
R
1=3-CH
3during OPh, R
2=2-FPhCO, 4-FPhCO, 2-ClPhCO, 4-ClPhCO, 3-BrPhCO, 4-BrPhCO, 3-CH
3oPhCO, 4-CH
3oPhCO, 3-pyridylCO, 4-pyridylCO, 2-thienylCO, 2-NO
2phCO, PhCO, 1-naphtholCO or 4-biphenylCO;
R
1=3,4-(CH
3o)
2during Ph, R
2=2-FPhCO, 4-FPhCO, 2-ClPhCO, 4-ClPhCO, 3-BrPhCO, 4-BrPhCO, 3-CH
3oPhCO, 4-CH
3oPhCO, 3-pyridylCO, 4-pyridylCO, 2-thienylCO, 2-NO
2phCO, PhCO, 1-naphtholCO or 4-biphenylCO;
R
1=3,4,5-(CH
3o)
3during Ph, R
2=NO
2, CN, COOEt, COCH
3, 2-FPhCO, 4-FPhCO, 2-ClPhCO, 4-ClPhCO, 3-BrPhCO, 4-BrPhCO, 4-CH
3phCO, 2,4-(CH
3)
2phCO, 3-CH
3oPhCO, 4-CH
3oPhCO, 2-pyridylCO, 3-pyridylCO, 4-pyridylCO, 2-thienylCO, 1-naphtholCO or 4-biphenylCO;
R
1during=2-naphthol, R
2=2-FPhCO, 2-ClPhCO, 4-ClPhCO or 2,4-(CH
3)
2phCO;
R
1during=2-pyridyl, R
2=CN, COOEt, 4-CH
3phCO, 2,4-(CH
3)
2phCO, 2-thienylCO, PhCO or 1-naphtholCO.
2. according to claim 13, the preparation method of 4-disubstituted pyrroles compound, is characterized in that, by disubstituted olefin i with Methyl benzenesulfonyl methyl isocyanide be there is to Michael addition, cyclization and elimination and reacts and obtain, synthetic route is as follows:
3. according to claim 23, the preparation method of 4-disubstituted pyrroles compound, it is characterized in that, in anhydrous response system, the TosMIC that adds 1 equivalent disubstituted olefin i and 1.1～1.3 equivalents, add the potassium tert.-butoxide of 1.2～1.4 equivalents as alkaline condensing agent, under low temperature environment, can prepare 3,4-disubstituted pyrroles compound.
4. according to claim 33, the preparation method of 4-disubstituted pyrroles compound, is characterized in that, adds potassium tert.-butoxide and fully after stirring and dissolving, reaction can be warming up to room temperature and carry out in reaction system.
5. according to claim 13, the application of 4-disubstituted pyrroles compound, is characterized in that, described 3,4-disubstituted pyrroles compound has proliferation inhibition activity to various tumor cell strains, has the ability of good selective killing tumour cell, can be used for preparing antitumor drug.
6. application according to claim 5, it is characterized in that, described various tumor cell strains comprises gastric carcinoma cells, Human Prostate Cancer Cells, human cervical carcinoma cell, people's malignant melanoma cell, human breast cancer cell, Chinese hamster ovary cancer cells and mouse colonic cell.
7. application according to claim 5, it is characterized in that, described various tumor cell strains also comprises that people's gastric adenocarcinoma cells, National People's Congress's cell lung cancer cell, human breast cancer cell, the chronic marrow of people source leukemia, human colon cancer cell, people tie Rectal Adenocarcinoma Cells, human liver cancer cell, human osteosarcoma cell, human lung carcinoma cell and mouse leukemia cell.
8. according to claim 13,4-disubstituted pyrroles compound, is characterized in that, described 3, and 4-disubstituted pyrroles compound comprises (4-(3,4-difluorophenyl)-1H-pyrroles-3-yl) (2-fluorophenyl) ketone, (4-(3,4-difluorophenyl)-1H-pyrroles-3-yl) (4-fluorophenyl) ketone, (4-(3,4-difluorophenyl)-1H-pyrroles-3-yl) (2-chloro-phenyl-) ketone, (4-(3,4-difluorophenyl)-1H-pyrroles-3-yl) (4-chloro-phenyl-) ketone, (4-(3,4-difluorophenyl)-1H-pyrroles-3-yl) (3-bromophenyl) ketone, (4-(3,4-difluorophenyl)-1H-pyrroles-3-yl) (4-bromophenyl) ketone, (4-(3,4-difluorophenyl)-1H-pyrroles-3-yl) (3-p-methoxy-phenyl) ketone, (4-(3,4-difluorophenyl)-1H-pyrroles-3-yl) (4-p-methoxy-phenyl) ketone, (4-(3,4-difluorophenyl)-1H-pyrroles-3-yl) (3-pyridyl) ketone, (4-(3,4-difluorophenyl)-1H-pyrroles-3-yl) (4-pyridyl) ketone, (4-(3,4-difluorophenyl)-1H-pyrroles-3-yl) (2-thienyl) ketone, (4-(3,4-difluorophenyl)-1H-pyrroles-3-yl) (2-nitrophenyl) ketone, (4-(3,4-difluorophenyl)-1H-pyrroles-3-yl) (phenyl) ketone, (4-(3,4-difluorophenyl)-1H-pyrroles-3-yl) (1-naphthyl) ketone, (4-(3,4-difluorophenyl)-1H-pyrroles-3-yl) (4-xenyl) ketone, 3-nitro-4-(4-acetylamino phenyl)-1H-pyrroles, 3-cyano group-4-(4-acetylamino phenyl)-1H-pyrroles, 3-ethoxycarbonyl-4-(4-acetylamino phenyl)-1H-pyrroles, 3-ethanoyl-4-(4-acetylamino phenyl)-1H-pyrroles, (4-(4-acetylamino phenyl)-1H-pyrroles-3-yl) (2-fluorophenyl) ketone, (4-(4-acetylamino phenyl)-1H-pyrroles-3-yl) (4-fluorophenyl) ketone, (4-(4-acetylamino phenyl)-1H-pyrroles-3-yl) (2-chloro-phenyl-) ketone, (4-(4-acetylamino phenyl)-1H-pyrroles-3-yl) (4-chloro-phenyl-) ketone, (4-(4-acetylamino phenyl)-1H-pyrroles-3-yl) (3-bromophenyl) ketone, (4-(4-acetylamino phenyl)-1H-pyrroles-3-yl) (4-bromophenyl) ketone, (4-(4-acetylamino phenyl)-1H-pyrroles-3-yl) (4-aminomethyl phenyl) ketone, (4-(4-acetylamino phenyl)-1H-pyrroles-3-yl) (2,4-3,5-dimethylphenyl) ketone, (4-(4-acetylamino phenyl)-1H-pyrroles-3-yl) (3-p-methoxy-phenyl) ketone, (4-(4-acetylamino phenyl)-1H-pyrroles-3-yl) (4-p-methoxy-phenyl) ketone, (4-(4-acetylamino phenyl)-1H-pyrroles-3-yl) (2-pyridyl) ketone, (4-(4-acetylamino phenyl)-1H-pyrroles-3-yl) (3-pyridyl) ketone, (4-(4-acetylamino phenyl)-1H-pyrroles-3-yl) (4-pyridyl) ketone, (4-(4-acetylamino phenyl)-1H-pyrroles-3-yl) (4-thienyl) ketone, (4-(4-acetylamino phenyl)-1H-pyrroles-3-yl) (phenyl) ketone, (4-(4-acetylamino phenyl)-1H-pyrroles-3-yl) (1-naphthyl) ketone, (4-(4-acetylamino phenyl)-1H-pyrroles-3-yl) (4-xenyl) ketone, (4-(3-p-methoxy-phenyl)-1H-pyrroles-3-yl) (2-fluorophenyl) ketone, (4-(3-p-methoxy-phenyl)-1H-pyrroles-3-yl) (4-fluorophenyl) ketone, (4-(3-p-methoxy-phenyl)-1H-pyrroles-3-yl) (2-chloro-phenyl-) ketone, (4-(3-p-methoxy-phenyl)-1H-pyrroles-3-yl) (4-fluorophenyl) ketone, (4-(3-p-methoxy-phenyl)-1H-pyrroles-3-yl) (3-bromophenyl) ketone, (4-(3-p-methoxy-phenyl)-1H-pyrroles-3-yl) (4-bromophenyl) ketone, (4-(3-p-methoxy-phenyl)-1H-pyrroles-3-yl) (3-p-methoxy-phenyl) ketone, (4-(3-p-methoxy-phenyl)-1H-pyrroles-3-yl) (4-p-methoxy-phenyl) ketone, (4-(3-p-methoxy-phenyl)-1H-pyrroles-3-yl) (3-pyridyl) ketone, (4-(3-p-methoxy-phenyl)-1H-pyrroles-3-yl) (4-pyridyl) ketone, (4-(3-p-methoxy-phenyl)-1H-pyrroles-3-yl) (2-thienyl) ketone, (4-(3-p-methoxy-phenyl)-1H-pyrroles-3-yl) (2-nitrophenyl) ketone, (4-(3-p-methoxy-phenyl)-1H-pyrroles-3-yl) (phenyl) ketone, (4-(3-p-methoxy-phenyl)-1H-pyrroles-3-yl) (1-naphthyl) ketone, (4-(3-p-methoxy-phenyl)-1H-pyrroles-3-yl) (4-xenyl) ketone, (4-(3,4-Dimethoxyphenyl)-1H-pyrroles-3-yl) (2-fluorophenyl) ketone, (4-(3,4-Dimethoxyphenyl)-1H-pyrroles-3-yl) (4-fluorophenyl) ketone, (4-(3,4-Dimethoxyphenyl)-1H-pyrroles-3-yl) (2-chloro-phenyl-) ketone, (4-(3,4-Dimethoxyphenyl)-1H-pyrroles-3-yl) (4-chloro-phenyl-) ketone, (4-(3,4-Dimethoxyphenyl)-1H-pyrroles-3-yl) (3-bromophenyl) ketone, (4-(3,4-Dimethoxyphenyl)-1H-pyrroles-3-yl) (4-bromophenyl) ketone, (4-(3,4-Dimethoxyphenyl)-1H-pyrroles-3-yl) (3-p-methoxy-phenyl) ketone, (4-(3,4-Dimethoxyphenyl)-1H-pyrroles-3-yl) (4-p-methoxy-phenyl) ketone, (4-(3,4-Dimethoxyphenyl)-1H-pyrroles-3-yl) (3-pyridyl) ketone, (4-(3,4-Dimethoxyphenyl)-1H-pyrroles-3-yl) (4-pyridyl) ketone, (4-(3,4-Dimethoxyphenyl)-1H-pyrroles-3-yl) (2-thienyl) ketone, (4-(3,4-Dimethoxyphenyl)-1H-pyrroles-3-yl) (2-nitrophenyl) ketone, (4-(3,4-Dimethoxyphenyl)-1H-pyrroles-3-yl) (phenyl) ketone, (4-(3,4-Dimethoxyphenyl)-1H-pyrroles-3-yl) (1-naphthyl) ketone, (4-(3,4-Dimethoxyphenyl)-1H-pyrroles-3-yl) (4-xenyl) ketone, 3-nitro-4-(3,4,5-trimethoxyphenyl)-1H-pyrroles, 3-cyano group-4-(3,4,5-trimethoxyphenyl)-1H-pyrroles, 3-ethoxycarbonyl-4-(3,4,5-trimethoxyphenyl)-1H-pyrroles, 3-ethanoyl-4-(3,4,5-trimethoxyphenyl)-1H-pyrroles, (4-(3,4,5-trimethoxyphenyl)-1H-pyrroles-3-yl) (2-fluorophenyl) ketone, (4-(3,4,5-trimethoxyphenyl)-1H-pyrroles-3-yl) (4-fluorophenyl) ketone, (4-(3,4,5-trimethoxyphenyl)-1H-pyrroles-3-yl) (2-chloro-phenyl-) ketone, (4-(3,4,5-trimethoxyphenyl)-1H-pyrroles-3-yl) (4-chloro-phenyl-) ketone, (4-(3,4,5-trimethoxyphenyl)-1H-pyrroles-3-yl) (3-bromophenyl) ketone, (4-(3,4,5-trimethoxyphenyl)-1H-pyrroles-3-yl) (4-bromophenyl) ketone, (4-(3,4,5-trimethoxyphenyl)-1H-pyrroles-3-yl) (4-aminomethyl phenyl) ketone, (4-(3,4,5-trimethoxyphenyl)-1H-pyrroles-3-yl) (2,4-3,5-dimethylphenyl) ketone, (4-(3,4,5-trimethoxyphenyl)-1H-pyrroles-3-yl) (3-p-methoxy-phenyl) ketone, (4-(3,4,5-trimethoxyphenyl)-1H-pyrroles-3-yl) (4-p-methoxy-phenyl) ketone, (4-(3,4,5-trimethoxyphenyl)-1H-pyrroles-3-yl) (2-pyridyl) ketone, (4-(3,4,5-trimethoxyphenyl)-1H-pyrroles-3-yl) (3-pyridyl) ketone, (4-(3,4,5-trimethoxyphenyl)-1H-pyrroles-3-yl) (4-pyridyl) ketone, (4-(3,4,5-trimethoxyphenyl)-1H-pyrroles-3-yl) (2-thienyl) ketone, (4-(3,4,5-trimethoxyphenyl)-1H-pyrroles-3-yl) (1-naphthyl) ketone, (4-(3,4,5-trimethoxyphenyl)-1H-pyrroles-3-yl) (4-xenyl) ketone, (4-(2-naphthyl)-1H-pyrroles-3-yl) (2-fluorophenyl) ketone, (4-(2-naphthyl)-1H-pyrroles-3-yl) (2-chloro-phenyl-) ketone, (4-(2-naphthyl)-1H-pyrroles-3-yl) (4-chloro-phenyl-) ketone, (4-(2-naphthyl)-1H-pyrroles-3-yl) (2,4-3,5-dimethylphenyl) ketone, 3-cyano group-4-(2-pyridyl)-1H-pyrroles, 3-ethoxycarbonyl-4-(2-pyridyl)-1H-pyrroles, (4-(2-pyridyl)-1H-pyrroles-3-yl) (4-aminomethyl phenyl) ketone, (4-(2-pyridyl)-1H-pyrroles-3-yl) (2,4-3,5-dimethylphenyl) ketone, (4-(2-pyridyl)-1H-pyrroles-3-yl) (2-thienyl) ketone, (4-(2-pyridyl)-1H-pyrroles-3-yl) (phenyl) ketone and (4-(2-pyridyl)-1H-pyrroles-3-yl) (1-naphthyl) ketone.
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| CN107011236A (en) * | 2017-05-31 | 2017-08-04 | 南京佰泰克生物技术有限公司 | A kind of compound and its preparation for improving CIK cell to stomach cancer lethality |
| CN109535068A (en) * | 2018-12-26 | 2019-03-29 | 中国药科大学 | Pyridine replaces chalcone compounds or its pharmaceutical salt and its preparation method and application |
| CN109535068B (en) * | 2018-12-26 | 2022-07-29 | 中国药科大学 | Pyridine substituted chalcone compound or pharmaceutically acceptable salt thereof, and preparation method and application thereof |
| CN113149894A (en) * | 2020-06-22 | 2021-07-23 | 上海长车生物科技有限公司 | (E) Pharmaceutical use of (E) -3-arylheterocyclylprop-2-enoic acid derivatives |
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