CN105585562B - 1- (benzofuran -5- bases) -3- aryl -2- (triazol-1-yl) propenone and its application as anticarcinogen - Google Patents
1- (benzofuran -5- bases) -3- aryl -2- (triazol-1-yl) propenone and its application as anticarcinogen Download PDFInfo
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- CN105585562B CN105585562B CN201410572524.8A CN201410572524A CN105585562B CN 105585562 B CN105585562 B CN 105585562B CN 201410572524 A CN201410572524 A CN 201410572524A CN 105585562 B CN105585562 B CN 105585562B
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- bases
- ketone
- propylene
- triazol
- dimethyl
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- IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical compound C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 title claims abstract description 60
- -1 triazol-1-yl Chemical group 0.000 title claims description 5
- 239000003005 anticarcinogenic agent Substances 0.000 title description 3
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 claims abstract description 91
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 claims abstract description 29
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 29
- 229910052805 deuterium Inorganic materials 0.000 claims abstract description 29
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 29
- 239000001257 hydrogen Substances 0.000 claims abstract description 29
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 21
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 17
- 239000000460 chlorine Substances 0.000 claims abstract description 17
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims abstract description 16
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims abstract description 16
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims abstract description 16
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims abstract description 16
- 229910052794 bromium Inorganic materials 0.000 claims abstract description 16
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 16
- 239000011737 fluorine Substances 0.000 claims abstract description 16
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 16
- 239000000126 substance Substances 0.000 claims abstract description 13
- 150000002576 ketones Chemical class 0.000 claims abstract description 7
- 150000003839 salts Chemical class 0.000 claims abstract description 7
- 125000003626 1,2,4-triazol-1-yl group Chemical group [*]N1N=C([H])N=C1[H] 0.000 claims description 59
- 125000000217 alkyl group Chemical group 0.000 claims description 51
- 238000002360 preparation method Methods 0.000 claims description 43
- 125000003545 alkoxy group Chemical group 0.000 claims description 28
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 7
- 201000005296 lung carcinoma Diseases 0.000 claims description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
- MFYLRNKOXORIPK-UHFFFAOYSA-N (3-nitrophenyl)-phenylmethanone Chemical class [O-][N+](=O)C1=CC=CC(C(=O)C=2C=CC=CC=2)=C1 MFYLRNKOXORIPK-UHFFFAOYSA-N 0.000 claims description 6
- ZYMCBJWUWHHVRX-UHFFFAOYSA-N (4-nitrophenyl)-phenylmethanone Chemical class C1=CC([N+](=O)[O-])=CC=C1C(=O)C1=CC=CC=C1 ZYMCBJWUWHHVRX-UHFFFAOYSA-N 0.000 claims description 6
- 125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 claims description 6
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 6
- 238000006243 chemical reaction Methods 0.000 claims description 6
- UJHSIDUUJPTLDY-UHFFFAOYSA-N (2-nitrophenyl)-phenylmethanone Chemical class [O-][N+](=O)C1=CC=CC=C1C(=O)C1=CC=CC=C1 UJHSIDUUJPTLDY-UHFFFAOYSA-N 0.000 claims description 5
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 5
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 5
- 150000001875 compounds Chemical class 0.000 claims description 5
- 206010008342 Cervix carcinoma Diseases 0.000 claims description 3
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 claims description 3
- 201000010881 cervical cancer Diseases 0.000 claims description 3
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical class OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 claims description 2
- 229910002651 NO3 Inorganic materials 0.000 claims description 2
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 claims description 2
- 229910019142 PO4 Inorganic materials 0.000 claims description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 2
- 229940077388 benzenesulfonate Drugs 0.000 claims description 2
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 claims description 2
- 229940001447 lactate Drugs 0.000 claims description 2
- 229940049920 malate Drugs 0.000 claims description 2
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 claims description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 2
- 239000010452 phosphate Substances 0.000 claims description 2
- 229940086735 succinate Drugs 0.000 claims description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 claims description 2
- 229950004288 tosilate Drugs 0.000 claims description 2
- 125000001376 1,2,4-triazolyl group Chemical class N1N=C(N=C1)* 0.000 claims 4
- 150000001336 alkenes Chemical class 0.000 claims 3
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 claims 2
- QSLPNSWXUQHVLP-UHFFFAOYSA-N $l^{1}-sulfanylmethane Chemical compound [S]C QSLPNSWXUQHVLP-UHFFFAOYSA-N 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 229940079593 drug Drugs 0.000 claims 1
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 claims 1
- NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 abstract description 4
- 239000002246 antineoplastic agent Substances 0.000 abstract description 3
- 229940041181 antineoplastic drug Drugs 0.000 abstract description 3
- 125000003118 aryl group Chemical group 0.000 abstract 2
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 abstract 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 132
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 115
- 125000001425 triazolyl group Chemical group 0.000 description 114
- 238000005160 1H NMR spectroscopy Methods 0.000 description 67
- 125000001140 1,4-phenylene group Chemical group [H]C1=C([H])C([*:2])=C([H])C([H])=C1[*:1] 0.000 description 49
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 29
- 210000004027 cell Anatomy 0.000 description 28
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- 0 CCOC1=C(*C(C)(C)C2)C2=CC(C(C([n]2[n+]cnc2)=Cc(cc2)ccc2Cl)=*)=CC1 Chemical compound CCOC1=C(*C(C)(C)C2)C2=CC(C(C([n]2[n+]cnc2)=Cc(cc2)ccc2Cl)=*)=CC1 0.000 description 6
- 150000003851 azoles Chemical class 0.000 description 6
- 230000002401 inhibitory effect Effects 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 5
- 239000000523 sample Substances 0.000 description 5
- 206010006187 Breast cancer Diseases 0.000 description 4
- 208000026310 Breast neoplasm Diseases 0.000 description 4
- 230000000259 anti-tumor effect Effects 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- FDPIMTJIUBPUKL-UHFFFAOYSA-N pentan-3-one Chemical compound CCC(=O)CC FDPIMTJIUBPUKL-UHFFFAOYSA-N 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 150000003852 triazoles Chemical group 0.000 description 4
- 206010028980 Neoplasm Diseases 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 201000011510 cancer Diseases 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- FGIUAXJPYTZDNR-UHFFFAOYSA-N potassium nitrate Chemical compound [K+].[O-][N+]([O-])=O FGIUAXJPYTZDNR-UHFFFAOYSA-N 0.000 description 3
- SULYEHHGGXARJS-UHFFFAOYSA-N 2',4'-dihydroxyacetophenone Chemical compound CC(=O)C1=CC=C(O)C=C1O SULYEHHGGXARJS-UHFFFAOYSA-N 0.000 description 2
- UJMGZPCKYHBCKU-UHFFFAOYSA-N 2,2-dimethyl-2,3-dihydrobenzofuran Chemical class C1=CC=C2OC(C)(C)CC2=C1 UJMGZPCKYHBCKU-UHFFFAOYSA-N 0.000 description 2
- QGZCUOLOTMJILH-UHFFFAOYSA-N 2h-tetrazol-2-ium;bromide Chemical compound [Br-].C1=N[NH+]=NN1 QGZCUOLOTMJILH-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- 206010060862 Prostate cancer Diseases 0.000 description 2
- 230000000118 anti-neoplastic effect Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 235000002639 sodium chloride Nutrition 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 210000004881 tumor cell Anatomy 0.000 description 2
- KJUGUADJHNHALS-UHFFFAOYSA-N 1H-tetrazole Substances C=1N=NNN=1 KJUGUADJHNHALS-UHFFFAOYSA-N 0.000 description 1
- WJGPNUBJBMCRQH-UHFFFAOYSA-N 2,2-dimethyl-2,3-dihydro-1-benzofuran-7-ol Chemical compound C1=CC(O)=C2OC(C)(C)CC2=C1 WJGPNUBJBMCRQH-UHFFFAOYSA-N 0.000 description 1
- AZKSAVLVSZKNRD-UHFFFAOYSA-M 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide Chemical compound [Br-].S1C(C)=C(C)N=C1[N+]1=NC(C=2C=CC=CC=2)=NN1C1=CC=CC=C1 AZKSAVLVSZKNRD-UHFFFAOYSA-M 0.000 description 1
- 208000010507 Adenocarcinoma of Lung Diseases 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 108020005199 Dehydrogenases Proteins 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- ZRYZBQLXDKPBDU-UHFFFAOYSA-N O=Cc(cc1)ccc1Br Chemical compound O=Cc(cc1)ccc1Br ZRYZBQLXDKPBDU-UHFFFAOYSA-N 0.000 description 1
- 108010019160 Pancreatin Proteins 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 241000594182 Sarcophaga sigma Species 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- ZETIVVHRRQLWFW-UHFFFAOYSA-N [O-][N+](c1cccc(C=O)c1)=O Chemical compound [O-][N+](c1cccc(C=O)c1)=O ZETIVVHRRQLWFW-UHFFFAOYSA-N 0.000 description 1
- XJLXINKUBYWONI-DQQFMEOOSA-N [[(2r,3r,4r,5r)-5-(6-aminopurin-9-yl)-3-hydroxy-4-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2s,3r,4s,5s)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate Chemical compound NC(=O)C1=CC=C[N+]([C@@H]2[C@H]([C@@H](O)[C@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](OP(O)(O)=O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 XJLXINKUBYWONI-DQQFMEOOSA-N 0.000 description 1
- 208000009956 adenocarcinoma Diseases 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 150000003935 benzaldehydes Chemical class 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 239000012888 bovine serum Substances 0.000 description 1
- 230000031709 bromination Effects 0.000 description 1
- 238000005893 bromination reaction Methods 0.000 description 1
- 208000019065 cervical carcinoma Diseases 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 238000004737 colorimetric analysis Methods 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
- 229940125898 compound 5 Drugs 0.000 description 1
- 150000001907 coumarones Chemical class 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- HBEDSQVIWPRPAY-UHFFFAOYSA-N dihydro-benzofuran Natural products C1=CC=C2OCCC2=C1 HBEDSQVIWPRPAY-UHFFFAOYSA-N 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 210000004251 human milk Anatomy 0.000 description 1
- 235000020256 human milk Nutrition 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 238000012417 linear regression Methods 0.000 description 1
- 201000005249 lung adenocarcinoma Diseases 0.000 description 1
- 210000003470 mitochondria Anatomy 0.000 description 1
- 238000003541 multi-stage reaction Methods 0.000 description 1
- GVOISEJVFFIGQE-YCZSINBZSA-N n-[(1r,2s,5r)-5-[methyl(propan-2-yl)amino]-2-[(3s)-2-oxo-3-[[6-(trifluoromethyl)quinazolin-4-yl]amino]pyrrolidin-1-yl]cyclohexyl]acetamide Chemical compound CC(=O)N[C@@H]1C[C@H](N(C)C(C)C)CC[C@@H]1N1C(=O)[C@@H](NC=2C3=CC(=CC=C3N=CN=2)C(F)(F)F)CC1 GVOISEJVFFIGQE-YCZSINBZSA-N 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- KLAKIAVEMQMVBT-UHFFFAOYSA-N p-hydroxy-phenacyl alcohol Natural products OCC(=O)C1=CC=C(O)C=C1 KLAKIAVEMQMVBT-UHFFFAOYSA-N 0.000 description 1
- 229940055695 pancreatin Drugs 0.000 description 1
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 1
- 230000008635 plant growth Effects 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000012488 sample solution Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 150000003536 tetrazoles Chemical class 0.000 description 1
- DPJRMOMPQZCRJU-UHFFFAOYSA-M thiamine hydrochloride Chemical compound Cl.[Cl-].CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N DPJRMOMPQZCRJU-UHFFFAOYSA-M 0.000 description 1
- 229910021642 ultra pure water Inorganic materials 0.000 description 1
- 239000012498 ultrapure water Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Plural Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention relates to 1 ketone of shown in chemical structural formula I or II 1 (5 base of benzofuran) 3 aryl 2 (1,2,4 triazole, 1 base) 2 propylene or its salt：Wherein, R is selected from：Hydrogen, deuterium, C1~C2Alkyl, C3~C4Alkyl；X1、X5It is selected from：Hydrogen, deuterium, C1~C2Alkyl, C3~C4Alkyl, hydroxyl, C1~C2Alkoxy, C3~C4Alkoxy, fluorine, chlorine, bromine or nitro；X3It is selected from：Hydrogen, deuterium, C1~C2Alkyl, C3~C4Alkyl, hydroxyl, C1~C2Alkoxy, C3~C4Alkoxy, fluorine, chlorine, bromine or nitro；X2、X4It is selected from：Hydrogen, deuterium, C1~C2Alkyl, C3~C4Alkyl or nitro；The application of 1 (5 base of benzofuran) 3 aryl 2 (1,2,4 triazole, 1 base) 2 propylene, 1 ketone or its salt in preparing anticancer drug.
Description
Technical field
The present invention relates to a new class of compounds and its preparation method and application, specifically (Z/E) -1- (benzofuran -5-
Base) -3- aryl -2- (1,2,4- triazol-1-yl) -2- propylene -1- ketone and preparation method thereof and its as preparing anticancer drug
Using.
Background technology
Chen Wen etc. [Org.Biomol.Chem., 2011,9,4250-4255] have synthesized coumaran imidazole salts
Class compound 1, and it is tested to a variety of human tumor cells such as human breast cancer cell (MCF-7), human lung carcinoma cells (A549)
The IC of cytotoxicity, wherein compound 1a to human breast cancer cell (MCF-7) and human lung carcinoma cell (A549)50Respectively 7.95 μM
With 12.35 μM.Nagaraju etc. [Bioorg.Med.Chem.Lett., 2012,22,4314-4317] is described in compound 2
On the basis of, the benzofuran propenone derivatives 3 and 4 synthesized as starting material by 2,4-dihydroxyacetophenone, and test
Its inhibitory activity to a variety of cancer cells such as Human Prostate Cancer Cells (PC-3), human lung carcinoma cells (NCI-H460), part chemical combination
Object has inhibitory activity to prostate gland cancer cell (PC-3) and lung carcinoma cell (NCI-H460).Tao Weifeng [Nankai University, master's opinion
Text, 2002] synthesis of propenone (5) and propenyl (6) containing pyridyl group and triazolyl is described, compound 5, which has, centainly kills
Bacterium activity, compound 6 have plant growth regulation.
Chinese patent describes the preparation of 4- (benzofuran -5- bases) -2- benzyl imino thiazoles and its as antineoplastic
The application [ZL 201010533786.5] of object, 4- (benzofuran -5- bases) -2- benzyls imino thiazoles and its as antineoplastic
The application [ZL201010533786.5,2012.7.25 are authorized] of object and 2- (2,2- dimethyl -2,3- Dihydrobenzofuranes -5-
Base) morpholine and the preparation method and application thereof [ZL201210106643.5,2014.7.23 are authorized].
It is etherified the present invention is directed to be raw material using benzofuranol, the multistep reactions synthesis 1- (benzofuran -5- such as acylated
Base) -3- aryl -2- (1,2,4- triazol-1-yl) -2- propylene -1- ketone, and research and develop its antitumor activity.
Invention content
The object of the present invention is to provide 1- shown in chemical structural formula I or II (benzofuran -5- bases) -3- aryl -2- (1,
2,4- triazol-1-yls) -2- propylene -1- ketone or its salt：
Wherein, R is selected from：Hydrogen, deuterium, C1~C2Alkyl, C3~C4Straight chained alkyl or branched alkyl；X1、X5It is selected from：Hydrogen, deuterium, C1
~C2Alkyl, C3~C4Straight chained alkyl or branched alkyl, hydroxyl, C1~C2Alkoxy, C3~C4Unbranched alkoxy or branch alcoxyl
Base, fluorine, chlorine, bromine or nitro；X3It is selected from：Hydrogen, deuterium, C1~C2Alkyl, C3~C4Straight chained alkyl or branched alkyl, hydroxyl, C1~C2
Alkoxy, C3~C4Unbranched alkoxy or branched alkoxy, fluorine, chlorine, bromine or nitro；X2、X4It is selected from：Hydrogen, deuterium, C1~C2Alkyl,
C3~C4Straight chained alkyl or branched alkyl or nitro；Its salt is selected from：Hydrochloride, hydrobromate, sulfate, nitrate, phosphate,
Mesylate, benzene sulfonate, tosilate, malate, lactate, succinate or butene dioic acid salt；Shown in formula I
- 1- (benzofuran -5- bases) -3- aryl -2- (1,2,4- triazol-1-yl) -2- propylene -1- ketone be (Z) -1- (2,2- diformazans
Base -2,3- Dihydrobenzofuranes -5- bases) -3- aryl -2- (1,2,4- triazol-1-yl) -2- propylene -1- ketone；Shown in formula II-
1- (benzofuran -5- bases) -3- aryl -2- (1,2,4- triazol-1-yl) -2- propylene -1- ketone is (E) -1- (2,2- dimethyl -
2,3- Dihydrobenzofuranes -5- bases) -3- aryl -2- (1,2,4- triazol-1-yl) -2- propylene -1- ketone.
The object of the present invention is to provide 1- shown in chemical structural formula III or IV (benzofuran -5- bases) -3- aryl -2-
(1,2,4- triazol-1-yl) -2- propylene -1- ketone：
Wherein, X1、X5It is selected from：Hydrogen, deuterium, C1~C2Alkyl, C3~C4Straight chained alkyl or branched alkyl, hydroxyl, C1~C2Alcoxyl
Base, C3~C4Unbranched alkoxy or branched alkoxy, fluorine, chlorine, bromine or nitro；X3It is selected from：Hydrogen, deuterium, C1~C2Alkyl, C3~C4Directly
Alkyl group or branched alkyl, hydroxyl, C1~C2Alkoxy, C3~C4Unbranched alkoxy or branched alkoxy, fluorine, chlorine, bromine or nitre
Base；X2、X4It is selected from：Hydrogen, deuterium, C1~C2Alkyl, C3~C4Straight chained alkyl or branched alkyl or nitro.
The object of the present invention is to provide 1- shown in chemical structural formula V or VI (benzofuran -5- bases) -3- aryl -2-
(1,2,4- triazol-1-yl) -2- propylene -1- ketone：
Wherein, X1、X5It is selected from：Hydrogen, deuterium, C1~C2Alkyl, C3~C4Straight chained alkyl or branched alkyl, hydroxyl, C1~C2Alcoxyl
Base, C3~C4Unbranched alkoxy or branched alkoxy, fluorine, chlorine, bromine or nitro；X3It is selected from：Hydrogen, deuterium, C1~C2Alkyl, C3~C4Directly
Alkyl group or branched alkyl, hydroxyl, C1~C2Alkoxy, C3~C4Unbranched alkoxy or branched alkoxy, fluorine, chlorine, bromine or nitre
Base；X2、X4It is selected from：Hydrogen, deuterium, C1~C2Alkyl, C3~C4Straight chained alkyl or branched alkyl or nitro.
The object of the present invention is to provide 1- shown in chemical structural formula VII or VIII (benzofuran -5- bases) -3- aryl -2-
(1,2,4- triazol-1-yl) -2- propylene -1- ketone：
Wherein, X1、X5It is selected from：Hydrogen, deuterium, C1~C2Alkyl, C3~C4Straight chained alkyl or branched alkyl, hydroxyl, C1~C2Alcoxyl
Base, C3~C4Unbranched alkoxy or branched alkoxy, fluorine, chlorine, bromine or nitro；X3It is selected from：Hydrogen, deuterium, C1~C2Alkyl, C3~C4Directly
Alkyl group or branched alkyl, hydroxyl, C1~C2Alkoxy, C3~C4Unbranched alkoxy or branched alkoxy, fluorine, chlorine, bromine or nitre
Base；X2、X4It is selected from：Hydrogen, deuterium, C1~C2Alkyl, C3~C4Straight chained alkyl or branched alkyl or nitro.
The present invention provides 1- (benzofuran -5- bases) -3- aryl -2- (1,2,4- tri- shown in chemical structural formula I or II
Azoles -1- bases) -2- propylene -1- ketone preparation method, it is characterised in that it preparation reaction it is as follows：
Wherein, R is selected from：Hydrogen, deuterium, C1~C2Alkyl, C3~C4Straight chained alkyl or branched alkyl；X1、X5It is selected from：Hydrogen, deuterium, C1
~C2Alkyl, C3~C4Straight chained alkyl or branched alkyl, hydroxyl, C1~C2Alkoxy, C3~C4Unbranched alkoxy or branch alcoxyl
Base, fluorine, chlorine, bromine or nitro；X3It is selected from：Hydrogen, deuterium, C1~C2Alkyl, C3~C4Straight chained alkyl or branched alkyl, hydroxyl, C1~C2
Alkoxy, C3~C4Unbranched alkoxy or branched alkoxy, fluorine, chlorine, bromine or nitro；X2、X4It is selected from：Hydrogen, deuterium, C1~C2Alkyl,
C3~C4Straight chained alkyl or branched alkyl or nitro.
The present invention provides 1- (benzofuran -5- bases) -3- aryl -2- (1,2,4- tri- shown in chemical structural formula I~VIII
Azoles -1- bases) -2- propylene -1- ketone application in preparations of anti-tumor drugs.
The present invention has the following advantages that compared with prior art：The present invention provides 1- (benzo furans shown in chemical formula I~VIII
Mutter -5- bases) -3- aryl -2- (1,2,4- triazol-1-yl) -2- propylene -1- ketone has anti-human cervical cancer cell (Hela), human milk
The activity of adenocarcinoma cell (MCF-7) and human lung carcinoma cell (A549).
Specific implementation mode
Following embodiment is intended to illustrate invention rather than limitation of the invention further.
Embodiment 1
(Z/E) -1- (7- methoxyl group -2,2- dimethyl -2,3- Dihydrobenzofuranes -5- bases) -3- aryl -2- (1,2,4-
Triazol-1-yl) -2- propylene -1- ketone preparation
The bromo- 1- of 0.14mol 2- (7- methoxyl group -2,2- dimethyl -2,3- Dihydrobenzofuranes -5- bases) ethyl ketone (C1),
0.16mol 1,2,4- triazole, 4mmol PEG600,0.54mol potassium carbonate, 100mL ethyl acetate backflows 1.5h.Reaction solution is taken out
It filters to obtain brown liquid, under condition of ice bath, 0.15mol nitric acid is added dropwise and obtains white precipitate, filters to obtain white solid, adds 500mL acetic acid
Ethyl ester dissolves, and 30%NaOH dissolvings are added dropwise, and adjusts pH to 7, stirring to solution to clarify, liquid separation takes organic phase, is evaporated under reduced pressure to
31.2g white solids 1- (7- methoxyl group -2,2- dimethyl -2,3- Dihydrobenzofuranes -5- bases) -2- (1,2,4- triazole) ethyl ketone
(D1), yield 80.1%, 152~155 DEG C of fusing point,1H NMR (400MHz, CDCl3)δ：1.57 (s, 6H, 2 × CH3), 3.11 (s,
2H, CCH2), 3.93 (s, 3H, OCH3), 5.64 (s, 2H, CH2), 7.45 (s, 1H, C6H2), 7.47 (s, 1H, C6H2), 8.04 (s,
1H, triazole ring 3-H), 8.39 (s, 1H, triazole ring 5-H).
3.5mmol 1- (7- methoxyl group -2,2- dimethyl -2,3- Dihydrobenzofuranes -5- bases) -2- (1,2,4- triazole)
Piperidines is added in ethyl ketone (D1), 5.2mmol benzaldehydes and 30mL chloroforms, stirring, and flow back 6h.After reaction, reaction solution is through water
It washes, saturated common salt washing, dry, precipitation, column chromatography for separation obtains product (E)-A1 and (Z)-A1, yield 60.3%.(E)-A1:It is molten
175~177 DEG C of point,1H NMR (400MHz, CDCl3)δ:1.56 (s, 6H, 2 × CH3), 3.08 (s, 2H, CH2), 3.90 (s, 3H,
OCH3), 6.95 (s, 1H, C6H24-H), 6.97 (s, 1H, C6H26-H), 7.29~7.39 (m, 5H, C6H5), 7.51 (s, 1H, C=
CH), 8.17 (s, 1H, triazole ring 3-H), 8.20 (s, 1H, triazole ring 5-H)；(Z)-A1:62~64 DEG C of fusing point,1H NMR
(400MHz, CDCl3)δ:1.48 (s, 6H, 2 × CH3), 2.93 (s, 2H, CH2), 3.85 (s, 3H, OCH3), 7.22~7.26 (m,
2H, C6H24,6-H), 7.29~7.46 (m, 5H, C6H5), 7.55 (s, 1H, C=CH), 8.07 (s, 1H, triazole ring 3-H), 8.29
(s, 1H, triazole ring 5-H).
Embodiment 2
(Z/E) -1- (7- methoxyl group -2,2- dimethyl -2,3- Dihydrobenzofuranes -5- bases) -3- (4- aminomethyl phenyls) -2-
The preparation of (1,2,4- triazol-1-yl) -2- propylene -1- ketone
Operation reacts 5h, yield 67.3% with embodiment 1.(E)-A2:158~159 DEG C of fusing point,1H NMR (400MHz,
CDCl3)δ:1.56 (s, 6H, 2 × CH3), 2.34 (s, 3H, CH3), 3.07 (s, 2H, CH2), 3.89 (s, 3H, OCH3), 6.82 (d,
J=8.0Hz, 2H, C6H43,5-H), 7.10 (d, J=8.0Hz, 2H, C6H42,6-H), 7.28 (s, 1H, C6H24-H), 7.37 (s,
1H, C6H26-H), 7.50 (s, 1H, C=CH), 8.14 (s, 1H, triazole ring 3-H), 8.18 (s, 1H, triazole ring 5-H)；(Z)-A2:
110~113 DEG C of fusing point,1H NMR (400MHz, CDCl3)δ:1.48 (s, 6H, 2 × CH3), 2.33 (s, 3H, CH3), 2.97 (s,
2H, CH2), 3.88 (s, 3H, OCH3), 7.02 (d, J=8.0Hz, 2H, C6H43,5-H), 7.19 (d, J=8.0Hz, 2H, C6H42,
6-H), 7.40 (s, 1H, C6H24-H), 7.47 (s, 1H, C6H26-H), 7.48 (s, 1H, C=CH), 8.05 (s, 1H, triazole ring 3-
H), 8.26 (s, 1H, triazole ring 5-H).
Embodiment 3
(Z/E) -1- (7- methoxyl group -2,2- dimethyl -2,3- Dihydrobenzofuranes -5- bases) -3- (4- hydroxy phenyls) -2-
The preparation of (1,2,4- triazol-1-yl) -2- propylene -1- ketone
Operation reacts 5h, yield 36.8% with embodiment 1.(E)-A3:194~196 DEG C of fusing point,1H NMR (400MHz,
CDCl3)δ:1.55 (s, 6H, 2 × CH3), 2.96 (s, 2H, CH2), 3.82 (s, 3H, OCH3), 6.73 (s, 4H, C6H4), 7.28
(s, 1H, C6H2), 7.37 (s, 1H, C6H2), 7.53 (s, 1H, C=CH), 8.26 (s, 2H, triazole rings)；(Z)-A3:Fusing point 180
DEG C,1H NMR (400MHz, CDCl3)δ:1.57 (s, 6H, 2 × CH3), 3.09 (s, 2H, CH2), 3.90 (s, 3H, OCH3), 6.73
(s, 4H, C6H4), 7.28 (s, 1H, C6H2), 7.37 (s, 1H, C6H2), 7.53 (s, 1H, CCH), 8.29 (s, 2H, triazole rings).
Embodiment 4
(Z/E) -1- (7- methoxyl group -2,2- dimethyl -2,3- Dihydrobenzofuranes -5- bases) -3- (2- methoxyphenyls) -
The preparation of 2- (1,2,4- triazol-1-yl) -2- propylene -1- ketone
Operation reacts 5h, yield 29.0% with embodiment 1.(E)-A4:126~128 DEG C of fusing point,1H NMR (400MHz,
CDCl3)δ:1.56 (s, 6H, 2 × CH3), 3.08 (s, 2H, CH2), 3.80 (s, 3H, OCH3), 3.91 (s, 3H, OCH3), 6.62~
6.82 (m, 2H, C6H2), 6.89~7.41 (m, 4H, C6H4), 7.80 (s, 1H, C=CH), 8.15 (s, 1H, triazole ring 3-H),
8.22 (s, 1H, triazole ring 5-H)；(Z)-A4:68~70 DEG C of fusing point,1H NMR (400MHz, CDCl3)δ:1.54 (s, 6H, 2 ×
CH3), 2.90 (s, 2H, CH2), 3.80 (s, 3H, OCH3), 3.93 (s, 3H, OCH3), 6.72~6.82 (m, 2H, C6H2), 6.89
~7.41 (m, 4H, C6H4), 7.72 (s, 1H, C=CH), 8.08 (s, 1H, triazole ring 3-H), 8.12 (s, 1H, triazole ring 5-H).
Embodiment 5
(Z/E) -1- (7- methoxyl group -2,2- dimethyl -2,3- Dihydrobenzofuranes -5- bases) -3- (4- fluorophenyls) -2-
The preparation of (1,2,4- triazol-1-yl) -2- propylene -1- ketone
Operation reacts 5h, yield 43.0% with embodiment 1.(E)-A5:155~156 DEG C of fusing point,1H NMR (400MHz,
CDCl3)δ:1.56 (s, 6H, 2 × CH3), 3.11 (s, 2H, CH2), 3.96 (s, 3H, OCH3), 6.94 (d, J=8.0Hz, 2H,
C6H43,5-H), 7.18 (d, J=8.0Hz, 2H, C6H42,6-H), 7.27 (s, 1H, C=CH), 7.52 (s, 1H, C6H24-H),
7.65 (s, 1H, C6H26-H), 7.70 (s, 1H, triazole ring 3-H), 8.24 (s, 1H, triazole ring 5-H)；(Z)-A5:Fusing point 124~
126 DEG C,1H NMR (400MHz, CDCl3)δ:1.55 (s, 6H, 2 × CH3), 3.06 (s, 2H, CH2), 3.91 (s, 3H, OCH3),
6.98 (d, J=8.0Hz, 2H, C6H43,5-H), 7.20 (d, J=8.0Hz, 2H, C6H42,6-H), 7.46 (s, 1H, C=CH),
7.50 (s, 1H, C6H24-H), 7.96 (s, 1H, C6H26-H), 8.19 (s, 1H, triazole ring 3-H), 8.40 (s, 1H, triazole ring 5-
H)。
Embodiment 6
(Z/E) -1- (7- methoxyl group -2,2- dimethyl -2,3- Dihydrobenzofuranes -5- bases) -3- (2- chlorphenyls) -2-
The preparation of (1,2,4- triazol-1-yl) -2- propylene -1- ketone
Operation reacts 5h, yield 20.0% with embodiment 1.(E)-A6:65~68 DEG C of fusing point,1H NMR (400MHz,
CDCl3)δ:1.56 (s, 6H, 2 × CH3), 3.09 (s, 2H, CH2), 3.92 (s, 3H, OCH3), 6.74~7.15 (m, 4H, C6H4),
7.39 (s, 1H, C6H24-H), 7.74 (s, 1H, C6H26-H), 7.75 (s, 1H, C=CH), 8.08 (s, 1H, triazole ring 3-H),
8.22 (s, 1H, triazole ring 5-H).(Z)-A6:Liquid,1H NMR (400MHz, CDCl3)δ:1.47 (s, 6H, 2 × CH3), 2.93
(s, 2H, CH2), 3.84 (s, 3H, OCH3), 7.20~7.39 (m, 4H, C6H4), 7.41 (s, 1H, C=CH), 7.65 (s, 1H,
C6H24-H), 7.79 (s, 1H, C6H26-H), 8.11 (s, 1H, triazole ring 3-H), 8.36 (s, 1H, triazole ring 5-H).
Embodiment 7
(Z/E) -1- (7- methoxyl group -2,2- dimethyl -2,3- Dihydrobenzofuranes -5- bases) -3- (4- chlorphenyls) -2-
The preparation of (1,2,4- triazol-1-yl) -2- propylene -1- ketone
Operation reacts 6h, yield 69.0% with embodiment 1.(E)-A7:131~134 DEG C of fusing point,1H NMR (400MHz,
CDCl3)δ:1.56 (s, 6H, 2 × CH3), 3.07 (s, 2H, CH2), 3.89 (s, 3H, OCH3), 6.89 (d, J=8.0Hz, 2H,
C6H43,5-H), 7.28 (d, J=8.0Hz, 2H, C6H42,6-H), 7.35 (s, 1H, C6H24-H), 7.45 (s, 1H, C6H26-H),
7.50 (s, 1H, CCH), 8.17~8.18 (m, 2H, triazole rings 3,5-H)；(Z)-A7:85~88 DEG C of fusing point,1H NMR
(400MHz, CDCl3)δ:1.50 (s, 6H, 2 × CH3), 2.95 (s, 2H, CH2), 3.87 (s, 3H, OCH3), 7.19 (d, J=
8.0Hz, 2H, C6H43,5-H), 7.25 (d, J=8.0Hz, 2H, C6H42,6-H), 7.30 (s, 1H, C6H24-H), 7.35 (s, 1H,
C6H26-H), 7.46 (s, 1H, CCH), 8.07 (s, 1H, triazole ring 3-H), 8.25 (s, 1H, triazole ring 5-H).
Embodiment 8
(Z/E) -1- (7- methoxyl group -2,2- dimethyl -2,3- Dihydrobenzofuranes -5- bases) -3- (2,4- dichlorophenyl) -
The preparation of 2- (1,2,4- triazol-1-yl) -2- propylene -1- ketone
Operation reacts 5h, yield 21.4% with embodiment 1.(E)-A8:187~189 DEG C of fusing point,1H NMR (400MHz,
CDCl3)δ:1.57 (s, 6H, 2 × CH3), 3.08 (s, 2H, CH2), 3.91 (s, 3H, OCH3), 6.65 (d, J=8.4Hz, 1H,
C6H36-H), 7.10 (dd, J=8.4Hz, J=2.0Hz, 1H, C6H35-H), 7.41 (s, 1H, C6H24-H), 7.47 (d, J=
2.0Hz, 1H, C6H33-H), 7.56 (s, 1H, C6H26-H), 7.70 (s, 1H, C=CH), 8.06 (s, 1H, triazole ring 3-H),
8.22 (s, 1H, triazole ring 5-H)；(Z)-A8:90~92 DEG C of fusing point,1H NMR (400MHz, CDCl3)δ:1.50 (s, 6H, 2 ×
CH3), 2.96 (s, 2H, CH2), 3.86 (s, 3H, OCH3), 6.75 (d, J=8.4Hz, 1H, C6H36-H), 7.02 (dd, J=
8.4Hz, J=2.0Hz, 1H, C6H35-H), 7.36 (d, J=2.0Hz, 1H, C6H33-H), 7.61 (s, 1H, C6H24-H), 7.78
(s, 1H, C6H26-H), 7.82 (s, 1H, C=CH), 8.09 (s, 1H, triazole ring 3-H), 8.30 (s, 1H, triazole ring 5-H).
Embodiment 9
(Z/E) -1- (7- methoxyl group -2,2- dimethyl -2,3- Dihydrobenzofuranes -5- bases) -3- (4- bromophenyls) -2-
The preparation of (1,2,4- triazol-1-yl) -2- propylene -1- ketone
Operation reacts 5h, yield 43.3% with embodiment 1.(E)-A9:157~160 DEG C of fusing point,1H NMR (400MHz,
CDCl3)δ:1.57 (s, 6H, 2 × CH3), 3.09 (s, 2H, CH2), 3.90 (s, 3H, OCH3), 6.82 (s, 1H, C6H24-H),
6.82 (s, 1H, C6H26-H), 7.29~7.45 (m, 4H, C6H4), 7.47 (s, 1H, C=CH), 8.25 (s, 1H, triazole ring 3-
H), 8.30 (s, 1H, triazole ring 5-H)；(Z)-A9:70~73 DEG C of fusing point,1H NMR (400MHz, CDCl3)δ:1.56 (s, 6H, 2
×CH3), 2.95 (s, 2H, CH2), 3.88 (s, 3H, OCH3), 7.16 (s, 1H, C6H24-H), 7.18 (s, 1H, C6H26-H),
7.35~7.47 (m, 4H, C6H4), 7.49 (s, 1H, C=CH), 8.09 (s, 1H, triazole ring 3-H), 8.28 (s, 1H, triazole ring 5-
H)。
Embodiment 10
(Z/E) -1- (7- methoxyl group -2,2- dimethyl -2,3- Dihydrobenzofuranes -5- bases) -3- (2- nitrobenzophenones) -2-
The preparation of (1,2,4- triazol-1-yl) -2- propylene -1- ketone
Operation reacts 7h, yield 21.7% with embodiment 1.(E)-A10:165~168 DEG C of fusing point,1H NMR (400MHz,
CDCl3)δ:1.56 (s, 6H, 2 × CH3), 3.09 (s, 2H, CH2), 3.94 (s, 3H, OCH3), 7.18~7.81 (m, 4H, C6H4),
7.87 (d, J=1.2Hz, 1H, C6H24-H), 8.13 (d, J=1.2Hz, 1H, C6H26-H), 8.42 (s, 1H, C=CH), 10.17
(s, 1H, triazole ring 3-H), 10.42 (s, 1H, triazole ring 5-H)；(Z)-A10：Liquid,1H NMR (400MHz, CDCl3)δ:1.57
(s, 6H, 2 × CH3), 3.07 (s, 2H, CH2), 3.90 (s, 3H, OCH3), 7.21~7.89 (m, 4H, C6H4), 7.78 (s, 1H,
C6H24-H), 8.13 (s, 1H, C6H26-H), 10.21 (s, 1H, triazole ring 3-H), 10.80 (s, 1H, triazole ring 5-H).
Embodiment 11
(Z/E) -1- (7- methoxyl group -2,2- dimethyl -2,3- Dihydrobenzofuranes -5- bases) -3- (3- nitrobenzophenones) -2-
The preparation of (1,2,4- triazol-1-yl) -2- propylene -1- ketone
Operation reacts 5h, yield 43.8% with embodiment 1.(E)-A11:154~155 DEG C of fusing point,1H NMR (400MHz,
CDCl3)δ:1.56 (s, 6H, 2 × CH3), 3.08 (s, 2H, CH2), 3.89 (s, 3H, OCH3), 7.21~7.47 (m, 4H, C6H4),
7.48~7.51 (m, 2H, C6H24,6-H), 7.96 (s, 1H, C=CH), 8.17 (s, 1H, triazole ring 3-H), 8.22 (s, 1H, three
Azoles ring 5-H)；(Z)-A11:75~78 DEG C of fusing point,1H NMR (400MHz, CDCl3)δ:1.48 (s, 6H, 2 × CH3), 2.96 (s,
2H, CH2), 3.87 (s, 3H, OCH3), 7.35~7.45 (m, 4H, C6H4), 7.60~7.63 (m, 2H, C6H24,6-H), 8.10
(s, 1H, C=CH), 8.20 (s, 1H, triazole ring 3-H), 8.27 (s, 1H, triazole ring 5-H).
Embodiment 12
(Z/E) -1- (7- methoxyl group -2,2- dimethyl -2,3- Dihydrobenzofuranes -5- bases) -3- (4- nitrobenzophenones) -2-
The preparation of (1,2,4- triazol-1-yl) -2- propylene -1- ketone
Operation reacts 8h, yield 22.6% with embodiment 1.(E)-A12:85~88 DEG C of fusing point,1H NMR (400MHz,
CDCl3)δ:1.56 (s, 6H, 2 × CH3), 3.07 (s, 2H, CH2), 3.89 (s, 3H, OCH3), 7.17~7.34 (m, 4H, C6H4),
7.36 (s, 1H, C6H24-H), 7.48 (s, 1H, C6H26-H), 8.10 (s, 1H, C=CH), 8.17 (s, 1H, triazole ring 3-H),
8.20 (s, 1H, triazole ring 5-H)；(Z)-A12:78~80 DEG C of fusing point,1H NMR (400MHz, CDCl3)δ:1.50 (s, 6H, 2 ×
CH3), 2.96 (s, 2H, CH2), 3.89 (s, 3H, OCH3), 7.46~7.48 (m, 4H, C6H4), 7.63 (s, 1H, C6H24-H),
8.09 (s, 1H, C6H26-H), 8.12 (s, 1H, C=CH), 8.15 (s, 1H, triazole ring 3-H), 8.24 (s, 1H, triazole ring 5-H).
Embodiment 13
(Z/E) -1- (7- ethyoxyl -2,2- dimethyl -2,3- Dihydrobenzofuranes -5- bases) -3- (4- aminomethyl phenyls) -2-
The preparation of (1,2,4- triazol-1-yl) -2- propylene -1- ketone
(Z/E) -1- (7- ethyoxyl -2,2- dimethyl -2,3- Dihydrobenzofuranes -5- bases) -2- (1,2,4- triazole) second
Ketone (D2) is operated by 1 method of embodiment.Yield 86.0%, 169~171 DEG C of fusing point,1H NMR (400MHz, CDCl3)δ:1.46
(t, J=8.0Hz, 3H, CH3), 1.57 (s, 6H, 2 × CH3), 3.10 (s, 2H, CH2), 4.18 (q, J=8.0Hz, 2H, CH2),
5.6 (s, 2H, CH2), 7.27 (s, 1H, C6H24-H), 7.44 (s, 1H, C6H26-H), 8.01 (s, 1H, triazole ring 3-H), 8.26
(s, 1H, triazole ring 5-H).
A13 is prepared by embodiment 1, reacts 6h, yield 48.0%, (E)-A13:154~156 DEG C of fusing point,1H NMR
(400MHz, CDCl3)δ:1.44 (t, J=7.2Hz, 3H, CH3), 1.55 (s, 6H, 2 × CH3), 3.06 (s, 2H, CH2), 4.13
(q, J=7.2Hz, 2H, CH2), 6.65 (s, 1H, C6H24-H), 6.72 (s, 1H, C6H26-H), 7.28~7.37 (m, 5H,
C6H5), 7.50 (s, 1H, C=CH), 8.15 (s, 1H, triazole ring 3-H), 8.18 (s, 1H, triazole ring 5-H)；(Z)-A13:Fusing point
53~55 DEG C,1H NMR (400MHz, CDCl3)δ:1.44 (t, J=7.2Hz, 3H, CH3), 1.55 (s, 6H, 2 × CH3), 3.06
(s, 2H, CH2), 4.13 (q, J=7.2Hz, 2H, CH2), 6.94 (s, 1H, C6H24-H), 6.96 (s, 1H, C6H26-H), 7.30~
7.37 (m, 5H, C6H5), 7.50 (s, 1H, C=CH), 8.09 (s, 1H, triazole ring 3-H), 8.20 (s, 1H, triazole ring 5-H).
Embodiment 14
(Z/E) -1- (7- ethyoxyl -2,2- dimethyl -2,3- Dihydrobenzofuranes -5- bases) -3- (4- aminomethyl phenyls) -2-
The preparation of (1,2,4- triazol-1-yl) -2- propylene -1- ketone
Operation reacts 5h, yield 43.1% with embodiment 1.(E)-A14:115~118 DEG C of fusing point,1H NMR (400MHz,
CDCl3)δ:1.47 (t, J=6.8Hz, 3H, CH3), 1.57 (s, 6H, 2 × CH3), 2.35 (s, 3H, CH3), 3.08 (s, 2H,
CH2), 4.14 (q, J=6.8Hz, 2H, CH2), 6.85 (d, J=6.0Hz, 2H, C6H43,5-H), 7.13 (d, J=6.0Hz, 2H,
C6H42,6-H), 7.30 (s, 1H, C6H24-H), 7.38 (s, 1H, C6H26-H), 7.56 (s, 1H, C=CH), 8.32 (s, 1H, three
Azoles ring 3-H), 8.38 (s, 1H, triazole ring 5-H)；(Z)-A14:98~100 DEG C of fusing point,1H NMR (400MHz, CDCl3)δ:1.45
(t, J=6.8Hz, 3H, CH3), 1.56 (s, 6H, 2 × CH3), 2.35 (s, 3H, CH3), 3.07 (s, 2H, CH2), 4.14 (q, J=
8.0Hz, 2H, CH2), 6.82 (d, J=8.0Hz, 2H, C6H43,5-H), 7.11 (d, J=6.0Hz, 2H, C6H42,6-H), 7.29
(s, 1H, C6H24-H), 7.36 (s, 1H, C6H26-H), 7.52 (s, 1H, C=CH), 8.23 (s, 1H, triazole ring 3-H), 8.24
(s, 1H, triazole ring 5-H).
Embodiment 15
(Z/E) -1- (7- ethyoxyl -2,2- dimethyl -2,3- Dihydrobenzofuranes -5- bases) -3- (2- methoxyphenyls) -
The preparation of 2- (1,2,4- triazol-1-yl) -2- propylene -1- ketone
Operation reacts 7h, yield 20.8% with embodiment 1.(E)-A15:50~53 DEG C of fusing point,1H NMR (400MHz,
CDCl3)δ:1.40 (t, J=6.8Hz, 3H, CH3), 1.47 (s, 6H, 2 × CH3), 3.07 (s, 2H, CH2), 3.80 (s, 3H,
CH3), 4.13 (q, J=6.8Hz, 2H, CH2), 6.78~6.91 (m, 2H, C6H24,6-H), 7.33~7.40 (m, 4H, C6H4),
7.80 (s, 1H, CCH), 8.08 (s, 1H, triazole ring 3-H), 8.21 (s, 1H, triazole ring 5-H)；(Z)-A15:Fusing point 127~130
DEG C,1H NMR (400MHz, CDCl3)δ:1.44 (t, J=6.8Hz, 3H, CH3), 1.56 (s, 6H, 2 × CH3), 2.90 (s, 2H,
CH2), 3.80 (s, 3H, CH3), 4.04 (q, J=6.8Hz, 2H, CH2), 6.01~6.76 (m, 2H, C6H2, 7.14 4,6-H)~
7.20 (m, 4H, C6H4), 7.72 (s, 1H, CCH), 8.16 (s, 1H, triazole ring 3-H), 8.38 (s, 1H, triazole ring 5-H).
Embodiment 16
(Z/E) -1- (7- ethyoxyl -2,2- dimethyl -2,3- Dihydrobenzofuranes -5- bases) -3- (4- fluorophenyls) -2-
The preparation of (1,2,4- triazol-1-yl) -2- propylene -1- ketone
Operation reacts 5h, yield 53.3% with embodiment 1.(E)-A16:140~143 DEG C of fusing point,1H NMR (400MHz,
CDCl3)δ:1.45 (t, J=6.8Hz, 3H, CH3), 1.56 (s, 6H, 2 × CH3), 3.07 (s, 2H, CH2), 4.13 (q, J=
6.8Hz, 2H, CH2), 6.93~7.02 (m, 4H, C6H4), 7.28 (s, 1H, C6H24-H), 7.35 (s, 1H, C6H26-H), 7.49
(s, 1H, C=CH), 8.21 (s, 2H, triazole rings 3,5-H)；(Z)-A16:54~58 DEG C of fusing point,1H NMR (400MHz, CDCl3)
δ:1.42 (t, J=6.8Hz, 3H, CH3), 1.50 (s, 6H, 2 × CH3), 2.94 (s, 2H, CH2), 4.10 (q, J=6.8Hz, 2H,
CH2), 6.92~7.00 (m, 4H, C6H4), 7.29 (s, 1H, C6H24-H), 7.31 (s, 1H, C6H26-H), 7.44 (s, 1H, C=
CH), 8.14 (s, 1H, triazole ring 3-H), 8.40 (s, 1H, triazole ring 5-H).
Embodiment 17
(Z/E) -1- (7- ethyoxyl -2,2- dimethyl -2,3- Dihydrobenzofuranes -5- bases) -3- (2- chlorphenyls) -2-
The preparation of (1,2,4- triazol-1-yl) -2- propylene -1- ketone
Operation reacts 6.5h, yield 35.3% with embodiment 1.(E)-A17:148~150 DEG C of fusing point,1H NMR
(400MHz, CDCl3)δ:1.40 (t, J=6.8Hz, 3H, CH3), 1.47 (s, 6H, 2 × CH3), 2.92 (s, 2H, CH2), 4.08
(q, J=6.8Hz, 2H, CH2), 7.00~7.18 (m, 2H, C6H24,6-H), 7.22~7.38 (m, 4H, C6H4), 7.77 (s, 1H,
C=CH), 8.10 (s, 1H, triazole ring 3-H), 8.33 (s, 1H, triazole ring 5-H)；(Z)-A17:59~62 DEG C of fusing point,1H NMR
(400MHz, DMSO-d6)δ：1.44 (t, J=6.1Hz, 3H, CH3), 1.55 (s, 6H, 2 × CH3), 3.07 (s, 2H, CH2),
3.70 (q, J=7.0Hz, 2H, CH2), 6.74 (d, J=7.8Hz, 1H, C6H24-H), 7.11 (d, J=4.2Hz, 1H, C6H26-
H), 7.28~7.44 (m, 4H, C6H4), 7.65 (s, 1H, C=CH), 8.10 (s, 1H, triazole 3-H), 8.29 (s, 1H, triazole 5-
H)。
Embodiment 18
(Z/E) -1- (7- ethyoxyl -2,2- dimethyl -2,3- Dihydrobenzofuranes -5- bases) -3- (4- chlorphenyls) -2-
The preparation of (1,2,4- triazol-1-yl) -2- propylene -1- ketone
Operation reacts 4h, yield 38.9% with embodiment 1.(E)-A18:125~128 DEG C of fusing point,1H NMR (400MHz,
CDCl3)δ:1.43 (t, J=6.8Hz, 3H, CH3), 1.56 (s, 6H, 2 × CH3), 3.07 (s, 2H, CH2), 4.10 (q, J=
6.8Hz, 2H, CH2), 6.89 (s, 1H, C6H24-H), 6.90 (s, 1H, C6H26-H), 7.19~7.34 (m, 4H, C6H4), 7.85
(s, 1H, C=CH), 8.22 (s, 1H, triazole ring 3-H), 8.25 (s, 1H, triazole ring 5-H)；(Z)-A18:50~52 DEG C of fusing point,1H NMR (400MHz, CDCl3)δ:1.43 (t, J=6.8Hz, 3H, CH3), 1.50 (s, 6H, 2 × CH3), 2.94 (s, 2H, CH2),
4.10 (q, J=6.8Hz, 2H, CH2), 7.22 (s, 2H, C6H24,6-H), 7.45 (d, J=8.0Hz, 2H, C6H43,5-H), 7.54
(d, J=8.0Hz, 2H, C6H42,6-H), 7.83 (s, 1H, C=CH), 8.11 (s, 1H, triazole ring 3-H), 8.31 (s, 1H, triazoles
Ring 5-H).
Embodiment 19
(Z/E) -1- (7- ethyoxyl -2,2- dimethyl -2,3- Dihydrobenzofuranes -5- bases) -3- (2,4- dichlorophenyl) -
The preparation of 2- (1,2,4- triazol-1-yl) -2- propylene -1- ketone
Operation reacts 7h, yield 24.3% with embodiment 1.(E)-A19:126~129 DEG C of fusing point,1H NMR (400MHz,
CDCl3)δ:1.25~1.28 (m, 3H, CH3), 1.33 (s, 6H, 2 × CH3), 2.92 (s, 2H, CH2), 4.08~4.10 (m, 2H,
CH2), 7.11~7.12 (m, 2H, C6H24,6-H), 7.35~7.40 (m, 3H, C6H3), 7.52 (s, 1H, C=CH), 8.12 (s,
1H, triazole ring 3-H), 8.24 (s, 1H, triazole ring 5-H).
Embodiment 20
(Z/E) -1- (7- ethyoxyl -2,2- dimethyl -2,3- Dihydrobenzofuranes -5- bases) -3- (4- bromophenyls) -2-
The preparation of (1,2,4- triazol-1-yl) -2- propylene -1- ketone
Operation reacts 5h, yield 54.1% with embodiment 1.(E)-A20:153~156 DEG C of fusing point,1H NMR (400MHz,
CDCl3)δ:1.43 (t, J=7.2Hz, 3H, CH3), 1.56 (s, 6H, 2 × CH3), 3.07 (s, 2H, CH2), 4.12 (q, J=
6.8Hz, 2H, CH2), 6.80 (s, 1H, C6H24-H), 6.82 (s, 1H, C6H26-H), 7.28 (s, 1H, C=CH), 7.35~7.46
(m, 4H, C6H4), 8.19~8.22 (m, 2H, triazole rings 3,5-H)；(Z)-A20:48~51 DEG C of fusing point,1H NMR (400MHz,
CDCl3)δ:1.43 (t, J=7.2Hz, 3H, CH3), 1.51 (s, 6H, 2 × CH3), 2.94 (s, 2H, CH2), 4.10 (q, J=
6.8Hz, 2H, CH2), 7.16 (s, 1H, C6H24-H), 7.18 (s, 1H, C6H26-H), 7.34~7.50 (m, 4H, C6H4), 7.49
(s, 1H, C=CH), 8.10 (s, 1H, triazole ring 3-H), 8.30 (s, 1H, triazole ring 5-H).
Embodiment 21
(Z/E) -1- (7- ethyoxyl -2,2- dimethyl -2,3- Dihydrobenzofuranes -5- bases) -3- (2- nitrobenzophenones) -2-
The preparation of (1,2,4- triazol-1-yl) -2- propylene -1- ketone
Operation reacts 4h, yield 38.5% with embodiment 1.(E)-A21:100~103 DEG C of fusing point,1H NMR (400MHz,
CDCl3)δ:1.41 (t, J=6.9Hz, 3H, CH3), 1.56 (s, 6H, 2 × CH3), 3.08 (s, 2H, CH2), 4.15~4.21 (m,
2H, CH2), 6.96 (d, J=6.3Hz, 1H, C6H24-H), 7.12 (s, 1H, C6H26-H), 7.18 (s, 1H, C=CH), 7.30 (d,
J=7.6Hz, 1H, C6H4), 7.53~7.41 (m, 3H, C6H4), 7.87 (s, 1H, triazole ring 3-H), 8.10 (s, 1H, triazole rings
5-H)；(Z)-A21:58~60 DEG C of fusing point,1H NMR (400MHz, CDCl3)δ:1.47 (t, J=7.0Hz, 3H, CH3), 1.56
(s, 6H, 2 × CH3), 3.08 (s, 2H, CH2), 4.16 (t, J=8.0Hz, 2H, CH2), 6.75 (d, J=4.0Hz, 1H, C6H24-
H), 6.96~7.07 (m, 1H, C6H26-H), 7.12~7.49 (m, 4H, C6H4), 7.87 (s, 1H, C=CH), 8.10 (d, J=
8.0Hz, 1H, C6H4), 8.45 (d, J=8.0Hz, 1H, triazole ring 3-H), 8.46 (s, 1H, triazole ring 5-H).
Embodiment 22
(Z/E) -1- (7- ethyoxyl -2,2- dimethyl -2,3- Dihydrobenzofuranes -5- bases) -3- (3- nitrobenzophenones) -2-
The preparation of (1,2,4- triazol-1-yl) -2- propylene -1- ketone
Operation reacts 5h, yield 32.5% with embodiment 1.(E)-A22:115~118 DEG C of fusing point,1H NMR (400MHz,
CDCl3)δ:1.41 (t, J=7.0Hz, 3H, CH3), 1.53 (s, 6H, 2 × CH3), 3.04 (d, J=5.2Hz, 2H, CH2), 4.00
~4.17 (m, 2H, CH2), 6.85 (d, J=8.4Hz, 2H, C6H24-H), 7.19 (s, 1H, CH=C), 7.32~7.44 (m, 4H,
C6H4), 8.16 (s, 2H, triazole rings 3,5-H)；(Z)-A22:62~65 DEG C of fusing point,1H NMR (400MHz, CDCl3)δ:1.41
(t, J=7.0Hz, 3H, CH3), 1.49 (s, 6H, 2 × CH3), 2.93 (s, 2H, CH2), 4.10 (q, J=7.1Hz, 2H, CH2),
7.15~7.25 (m, 2H, C6H24,6-H), 7.34 (s, 1H, C6H42-H), 7.44~7.49 (m, 3H, C6H4), 8.07 (s, 1H, C
=CH), 8.19 (s, 1H, triazole ring 3-H), 8.25 (s, 1H, triazole ring 5-H).
Embodiment 23
(Z/E) -1- (7- ethyoxyl -2,2- dimethyl -2,3- Dihydrobenzofuranes -5- bases) -3- (4- nitrobenzophenones) -2-
The preparation of (1,2,4- triazol-1-yl) -2- propylene -1- ketone
Operation reacts 5h, yield 34.7% with embodiment 1.(E)-A23:162~166 DEG C of fusing point,1H NMR (400MHz,
CDCl3)δ:1.42 (t, J=7.0Hz, 3H, CH3), 1.53 (s, 6H, 2 × CH3), 3.04 (s, 2H, CH2), 4.11 (q, J=
7.0Hz, 2H, CH2), 7.14 (s, 1H, C6H24-H), 7.16 (s, 1H, C6H26-H), 7.27 (s, 1H, C6H4), 7.33 (s, 1H,
C6H4), 7.42 (s, 1H, C6H4), 8.11~8.17 (m, 2H, C6H4), 8.20 (s, 1H, triazole ring 5-H)；(Z)-A23:Fusing point 63
~66 DEG C,1H NMR (400MHz, CDCl3)δ:1.47 (t, J=7.0Hz, 3H, CH3), 1.56 (s, 6H, 2 × CH3), 3.08 (s,
2H, CH2), 4.13 (s, 2H, CH2), 7.17 (d, J=8.8Hz, 2H, C6H2), 7.30 (s, 1H, C6H4), 7.36 (s, 1H, C6H4),
7.46 (d, J=4.2Hz, 1H, C6H4), 8.13~8.20 (m, 3H, C6H4, triazole ring 5-H), 8.24 (s, 1H, triazole ring 5-H).
Embodiment 24
(Z/E) -1- (7- propoxyl group -2,2- dimethyl -2,3- Dihydrobenzofuranes -5- bases) -3- phenyl -2- (1,2,4-
Triazol-1-yl) -2- propylene -1- ketone preparation
1- (7- propoxyl group -2,2- dimethyl -2,3- Dihydrobenzofuranes -5- bases) -2- (1,2,4- triazole) ethyl ketone (D3)
Preparation by 1 method of embodiment operate, yield 85.3%, 147~149 DEG C of fusing point,1H NMR (400MHz, CDCl3)δ:1.03
(t, J=8.0Hz, 3H, CH3), 1.26 (s, 6H, 2 × CH3), 1.87~1.92 (m, 2H, CH2), 3.09 (s, 2H, CH2), 4.03
~4.07 (m, 2H, CH2), 5.66 (s, 2H, CH2), 7.44 (s, 2H, C6H24-H), 7.51 (s, 2H, C6H26-H), 8.09 (s,
1H, triazole ring 3-H), 8.51 (s, 1H, triazole ring 5-H).
A24 is prepared by embodiment 1, reaction 6h, yield 41.8%, 106~109 DEG C of fusing point,1H NMR (400MHz, CDCl3)
δ:1.03 (t, J=8.0Hz, 3H, CH3), 1.56 (s, 6H, 2 × CH3), 1.83~1.88 (m, 2H, CH2), 3.09 (s, 2H,
CH2), 4.05 (t, J=8.0Hz, 2H, CH2), 7.15~7.23 (m, 2H, C6H2), 7.45~7.62 (m, 5H, C6H5), 8.08
(s, 1H, CCH), 8.11 (s, 1H, triazole ring 3-H), 8.50 (s, 1H, triazole ring 5-H).
Embodiment 25
(Z/E) -1- (7- propoxyl group -2,2- dimethyl -2,3- Dihydrobenzofuranes -5- bases) -3- (4- aminomethyl phenyls) -2-
The preparation of (1,2,4- triazol-1-yl) -2- propylene -1- ketone
Operation reacts 6h, yield 44.3% with embodiment 1.A25:116~118 DEG C of fusing point,1H NMR (400MHz,
CDCl3)δ:1.04 (t, 3H, J=7.2Hz, CH3), 1.58 (s, 6H, 2 × CH3), 1.83~1.88 (m, 2H, CH2), 3.11 (s,
2H, CH2), 4.08 (t, J=7.2Hz, 2H, CH2), 6.61~7.07 (m, 2H, C6H2), 7.45~7.64 (m, 4H, C6H4),
7.70 (s, 1H, C=CH), 8.22 (s, 1H, triazole ring 3-H), 8.30 (s, 1H, triazole ring 5-H).
Embodiment 26
(Z/E) -1- (7- propoxyl group -2,2- dimethyl -2,3- Dihydrobenzofuranes -5- bases) -3- (2- methoxyphenyls) -
The preparation of 2- (1,2,4- triazol-1-yl) -2- propylene -1- ketone
Operation reacts 5h, yield 59.5% with embodiment 1.(E)-A26:192~193 DEG C of fusing point,1H NMR (400MHz,
CDCl3)δ:1.02 (t, J=7.2Hz, 3H, CH3), 1.56 (s, 6H, 2 × CH3), 1.83~1.88 (m, 2H, CH2), 3.07 (s,
2H, CH2), 3.80 (s, 3H, OCH3), 4.04 (t, J=7.2Hz, 2H, CH2), 6.63~6.81 (m, 2H, C6H2), 6.89~
7.40 (m, 4H, C6H4), 7.82 (s, 1H, C=CH), 8.21 (s, 1H, triazole ring 3-H), 8.34 (s, 1H, triazole ring 5-H)；
(Z)-A26:58~60 DEG C of fusing point,1H NMR (400MHz, CDCl3)δ:0.99 (t, J=7.2Hz, 3H, CH3), 1.47 (s, 6H, 2
×CH3), 1.78~1.82 (m, 2H, CH2), 2.89 (s, 2H, CH2), 3.81 (s, 3H, OCH3), 3.92 (t, J=7.2Hz, 2H,
CH2), 6.72~6.80 (m, 2H, C6H2), 6.91~7.44 (m, 4H, C6H4), 7.41 (s, 1H, C=CH), 8.11 (s, 1H, three
Azoles ring 3-H), 8.42 (s, 1H, triazole ring 5-H).
Embodiment 27
(Z/E) -1- (7- propoxyl group -2,2- dimethyl -2,3- Dihydrobenzofuranes -5- bases) -3- (4- fluorophenyls) -2-
The preparation of (1,2,4- triazol-1-yl) -2- propylene -1- ketone
Operation reacts 7h, yield 52.9% with embodiment 1.(E)-A27:152~155 DEG C of fusing point,1H NMR (400MHz,
CDCl3)δ:1.02 (t, J=7.2Hz, 2H, CH3), 1.56 (s, 6H, 2 × CH3), 1.84~1.88 (m, 2H, CH2), 3.07 (s,
2H, CH2), 4.03 (t, J=7.2Hz, 2H, CH2), 6.94~7.00 (m, 2H, C6H2), 7.02~7.36 (m, 4H, C6H4),
7.53 (s, 1H, C=CH), 8.31 (s, 1H, triazole ring 3-H), 8.41 (s, 1H, triazole ring 5-H)；(Z)-A27:Fusing point 85~88
DEG C,1H NMR (400MHz, CDCl3)δ:1.01 (t, J=7.6Hz, 2H, CH3), 1.56 (s, 6H, 2 × CH3), 1.79~1.84
(m, 2H, CH2), 2.93 (s, 2H, CH2), 3.98 (t, J=7.2Hz, 2H, CH2), 6.92~6.96 (m, 2H, C6H2), 7.30~
7.44 (m, 4H, C6H4), 7.52 (s, 1H, C=CH), 8.10 (s, 1H, triazole ring 3-H), 8.30 (s, 1H, triazole ring 5-H).
Embodiment 28
(Z/E) -1- (7- propoxyl group -2,2- dimethyl -2,3- Dihydrobenzofuranes -5- bases) -3- (2- chlorphenyls) -2-
The preparation of (1,2,4- triazol-1-yl) -2- propylene -1- ketone
Operation reacts 7h, yield 30.0% with embodiment 1.(E)-A28:62~64 DEG C of fusing point,1H NMR (400MHz,
CDCl3)δ:1.02 (t, J=7.2Hz, 3H, CH3), 1.56 (s, 6H, 2 × CH3), 1.83~1.88 (m, 2H, CH2), 3.07 (s,
2H, CH2), 4.04 (t, J=7.2Hz, 2H, CH2), 6.74~7.14 (m, 2H, C6H2), 7.30~7.46 (m, 4H, C6H4),
7.65 (s, 1H, CCH), 8.09 (s, 1H, triazole ring 3-H), 8.23 (s, 1H, triazole ring 5-H)；(Z)-A28:Fusing point 142~144
DEG C,1H NMR (400MHz, CDCl3)δ:1.00 (t, J=7.2Hz, 3H, CH3), 1.47 (s, 6H, 2 × CH3), 1.77~1.83
(m, 2H, CH2), 2.92 (s, 2H, CH2), 3.95 (t, J=7.2Hz, 2H, CH2), 7.03~7.15 (m, 2H, C6H2), 7.21~
7.38 (m, 4H, C6H4), 7.79 (s, 1H, C=CH), 8.12 (s, 1H, triazole ring 3-H), 8.37 (s, 1H, triazole ring 5-H).
Embodiment 29
(Z/E) -1- (7- propoxyl group -2,2- dimethyl -2,3- Dihydrobenzofuranes -5- bases) -3- (4- chlorphenyls) -2-
The preparation of (1,2,4- triazol-1-yl) -2- propylene -1- ketone
Operation reacts 6h, yield 65.4% with embodiment 1.(E)-A29:155~158 DEG C of fusing point,1H NMR (400MHz,
CDCl3)δ:1.01 (t, J=7.2Hz, 2H, CH3), 1.54 (s, 6H, 2 × CH3), 1.78~1.86 (m, 2H, CH2), 3.05 (s,
2H, CH2), 4.01 (t, J=7.2Hz, 2H, CH2), 6.89 (d, J=8.0Hz, 2H, C6H43,5-H), 7.27 (d, J=8.0Hz,
2H, C6H42,6-H) 7.28 (s, 1H, C=CH), 7.34 (s, 1H, C6H24-H), 7.44 (s, 1H, C6H26-H), 8.18 (s, 2H,
Triazole ring 3,5-H)；(Z)-A29:115~118 DEG C of fusing point,1H NMR (400MHz, CDCl3)δ:1.23 (t, J=7.2Hz, 2H,
CH3), 1.56 (s, 6H, 2 × CH3), 1.98~2.05 (m, 2H, CH2), 2.96 (s, 2H, CH2), 4.10 (t, J=7.2Hz, 2H,
CH2), 6.95 (d, J=8.0Hz, 2H, C6H43,5-H), 7.27 (d, J=8.0Hz, 2H, C6H42,6-H), 7.28 (s, 1H,
CCH), 7.34 (s, 1H, C6H24-H), 7.47 (s, 1H, C6H26-H), 8.12 (s, 2H, triazole ring 3,5-H).
Embodiment 30
(Z/E) -1- (7- propoxyl group -2,2- dimethyl -2,3- Dihydrobenzofuranes -5- bases) -3- (2,4- dichlorophenyl) -
The preparation of 2- (1,2,4- triazol-1-yl) -2- propylene -1- ketone
Operation reacts 7h, yield 21.0% with embodiment 1.(E)-A30:122~126 DEG C of fusing point,1H NMR (400MHz,
CDCl3)δ:1.02 (t, 3H, J=7.2Hz, CH3), 1.55 (s, 6H, 2 × CH3), 1.83~1.88 (m, 2H, CH2), 3.07 (s,
2H, CH2), 4.04 (t, J=7.2Hz, 2H, CH2), 6.65~6.70 (m, 1H, C6H2, 4-H), 7.10~7.12 (m, 1H,
C6H26-H), 7.36 (d, J=2.0Hz, 1H, C6H35-H), 7.41 (s, 1H, C6H33-H), 7.47 (d, J=2.0Hz, 1H,
C6H36-H), 7.57 (s, 1H, C=CH), 8.09 (s, 1H, triazole ring 3-H), 8.28 (s, 1H, triazole ring 5-H).
Embodiment 31
(Z/E) -1- (7- propoxyl group -2,2- dimethyl -2,3- Dihydrobenzofuranes -5- bases) -3- (4- bromophenyls) -2-
The preparation of (1,2,4- triazol-1-yl) -2- propylene -1- ketone
Operation reacts 6h, yield 55.5% with embodiment 1.(E)-A31:156~159 DEG C of fusing point,1H NMR (400MHz,
CDCl3)δ:1.02 (t, J=7.2Hz, 3H, CH3), 1.56 (s, 6H, 2 × CH3), 1.82~1.86 (m, 2H, CH2), 3.07 (s,
2H, CH2), 4.02 (s, 2H, CH2), 6.84 (s, 2H, C6H2), 7.25~7.46 (m, 4H, C6H4), 7.52 (s, 1H, C=CH),
8.26 (s, 2H, triazole rings 3,5-H)；(Z)-A31:80~84 DEG C of fusing point,1H NMR (400MHz, CDCl3)δ:1.01 (t, J=
7.2Hz, 3H, CH3), 1.50 (s, 6H, 2 × CH3), 1.79~1.82 (m, 2H, CH2), 2.93 (s, 2H, CH2), 3.98 (t, J=
7.2Hz, 2H, CH2), 6.79~6.81 (m, 1H, C6H24-H), 7.16 (d, J=8.2Hz, 2H, C6H43,5-H), 7.33 (s, 1H,
C6H26-H), 7.37 (d, J=8.2Hz, 2H, C6H42,6-H), 7.50 (s, 1H, C=CH), 8.12 (s, 2H, triazole ring 3-H),
8.33 (s, 2H, triazole ring 5-H).
Embodiment 32
(Z/E) -1- (7- propoxyl group -2,2- dimethyl -2,3- Dihydrobenzofuranes -5- bases) -3- (2- nitrobenzophenones) -2-
The preparation of (1,2,4- triazol-1-yl) -2- propylene -1- ketone
Operation reacts 6h, yield 38.9% with embodiment 1.(E)-A32:154~156 DEG C of fusing point,1H NMR (400MHz,
CDCl3)δ:0.99 (t, J=7.2Hz, 2H, CH3), 1.46 (s, 6H, 2 × CH3), 1.75~1.80 (m, 2H, CH2), 2.88 (s,
2H, CH2), 3.90 (t, J=7.2Hz, 2H, CH2), 7.31 (s, 1H, C6H24-H), 7.34 (s, 1H, C6H26-H), 7.38~
7.98 (m, 4H, C6H4), 8.01 (s, 1H, C=CH), 8.14 (s, 1H, triazole ring 3-H), 8.38 (s, 1H, triazole ring 5-H),
(Z)-A32:153~155 DEG C of fusing point,1H NMR (400MHz, CDCl3)δ:1.04 (t, J=7.2Hz, 2H, CH3), 1.56 (s,
6H, 2 × CH3), 1.84-1.88 (m, 2H, CH2), 3.10 (s, 2H, CH2), 4.10 (t, J=7.2Hz, 2H, CH2), 6.99~
7.12 (m, 1H, C6H24-H), 7.47 (s, 1H, C6H26-H), 7.50~7.91 (m, 4H, C6H4), 7.91 (s, 1H, C=CH),
8.22~8.32 (m, 1H, triazole ring 3-H), 8.44~8.50 (m, 1H, triazole ring 5-H).
Embodiment 33
(Z/E) -1- (7- propoxyl group -2,2- dimethyl -2,3- Dihydrobenzofuranes -5- bases) -3- (3- nitrobenzophenones) -2-
The preparation of (1,2,4- triazol-1-yl) -2- propylene -1- ketone
Operation reacts 6.5h, yield 29.1% with embodiment 1.(E)-A33:149~150 DEG C of fusing point,1H NMR
(400MHz, CDCl3)δ:1.02 (t, J=7.2Hz, 2H, CH3), 1.63 (s, 6H, 2 × CH3), 1.84~1.90 (m, 2H,
CH2), 3.07 (s, 2H, CH2), 3.98 (t, J=7.2Hz, 2H, CH2), 7.22~7.30 (m, 2H, C6H2, 7.31 4,6-H)~
7.48 (m, 4H, C6H4), 7.98 (s, 1H, CCH), 8.13 (s, 1H, triazole ring 3-H), 8.29 (s, 1H, triazole ring 5-H)；(Z)-
A33:123~125 DEG C of fusing point,1H NMR (400MHz, CDCl3)δ:1.02 (t, J=7.2Hz, 2H, CH3), 1.48 (s, 6H, 2 ×
CH3), 1.82~1.86 (m, 2H, CH2), 2.93 (s, 2H, CH2), 3.98 (t, J=7.2Hz, 2H, CH2), 7.30~7.42 (m,
2H, C6H24,6-H), 7.48~7.64 (m, 4H, C6H4), 8.00 (s, 1H, CCH), 8.17~8.29 (m, 2H, triazole rings 3,5-
H)。
Embodiment 34
(Z/E) -1- (7- propoxyl group -2,2- dimethyl -2,3- Dihydrobenzofuranes -5- bases) -3- (4- nitrobenzophenones) -2-
The preparation of (1,2,4- triazol-1-yl) -2- propylene -1- ketone
Operation reacts 5h, yield 36.5% with embodiment 1.(E)-A34:141~144 DEG C of fusing point,1H NMR (400MHz,
CDCl3)δ:1.01 (t, J=7.2Hz, 2H, CH3), 1.49 (s, 6H, 2 × CH3), 1.78~1.86 (m, 2H, CH2), 3.06 (s,
2H, CH2), 4.00 (t, J=7.2Hz, 2H, CH2), 7.17 (d, J=8.0Hz, 2H, C6H43,5-H), 7.30 (d, J=8.0Hz,
2H, C6H42,6-H), 7.44 (s, 1H, C6H24-H), 7.48 (s, 1H, C6H26-H), 8.09 (s, 1H, CCH), 8.15 (s, 2H, three
Azoles ring 3,5-H)；(Z)-A34:122~125 DEG C of fusing point,1H NMR (400MHz, CDCl3)δ:0.90 (t, J=7.2Hz, 2H,
CH3), 1.55 (s, 6H, 2 × CH3), 1.67~1.72 (m, 2H, CH2), 2.97 (s, 2H, CH2), 4.12 (t, J=7.2Hz, 2H,
CH2), 7.05 (d, J=8.0Hz, 2H, C6H43,5-H), 7.30 (d, J=8.0Hz, 2H, C6H42,6-H), 7.51 (s, 1H,
C6H24-H), 7.61 (s, 1H, C6H26-H), 8.11 (s, 1H, C=CH), 8.21 (s, 2H, triazole rings 3,5-H).
Embodiment 35
1- (benzofuran -5- bases) -3- aryl -2- (1,2,4- triazol-1-yl) -2- propylene -1- ketone active anticancers measure
1. antitumor activity principle
Mtt assay biological activity test is also known as MTT colorimetric methods, is a kind of method of detection cell survival and growth.MTT is analyzed
Method is with living cells metabolin reducing agent tetrazolium bromide [3- (4,5- dimethyl -2- thiazoles) -2,5- diphenyl bromination tetrazoles；3- (4,
5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide, MTT] based on.MTT is a kind of
It can receive the dyestuff of hydrogen atom.The MTT of yellow can be converted in the cell with the relevant dehydrogenases of NADP in living cells mitochondria
At the first a ceremonial jade-ladle, used in libation (formazon) of insoluble bluish violet, and dead cell is then without this function.After dissolving formazon with DMSO, one
OD value is measured with microplate reader under standing wave length, can both quantify the survival rate for measuring cell.It is observed according to the variation of OD value
Inhibiting effect of the sample to tumour cell.
2. antitumor activity is tested
Sample：1- (benzofuran -5- bases) -3- aryl -2- (1,2,4- triazol-1-yl) -2- propylene -1- ketone：
Wherein, R is selected from：Hydrogen, deuterium, C1~C2Alkyl, C3~C4Straight chained alkyl or branched alkyl；X1、X5It is selected from：Hydrogen, deuterium, C1
~C2Alkyl, C3~C4Straight chained alkyl or branched alkyl, hydroxyl, C1~C2Alkoxy, C3~C4Unbranched alkoxy or branch alcoxyl
Base, fluorine, chlorine, bromine or nitro；X3It is selected from：Hydrogen, deuterium, C1~C2Alkyl, C3~C4Straight chained alkyl or branched alkyl, hydroxyl, C1~C2
Alkoxy, C3~C4Unbranched alkoxy or branched alkoxy, fluorine, chlorine, bromine or nitro；X2、X4It is selected from：Hydrogen, deuterium, C1~C2Alkyl,
C3~C4Straight chained alkyl or branched alkyl or nitro.
Cell line：Cervical cancer tumer line Hela, lung adenocarcinoma cell line A549 and breast cancer cell line MCF-7 (Central South University
Xiang Ya medical colleges cell bank provides).
Reagent：(U.S.'s hero's life technology is public for tetrazolium bromide (MTT), RPMI 1640 culture mediums, newborn bovine serum, antibiotic
Department)；Pancreatin (AMRESCO companies of the U.S.)；96 well culture plates (hero Life Technologies, Inc. of the U.S.)；Dimethyl sulfoxide (DMSO) (the U.S.
Sigma companies).
Instrument：HFsafe-1500 types superclean bench, HF151UV types CO2(Shanghai power Shen scientific instrument are limited for incubator
Company)；XSP-15C types inverted microscope (the rectangular optical instrument Co., Ltd in Shanghai)；Multiskan MK3 types microplate reader is (beautiful
Thermo companies of state)；Ultra-pure water preparing instrument (Milli-Q companies of the U.S.).
Experimental implementation：Test of the sample for cancer cell.In experimentation, 5 concentration gradients are arranged in per sample (p.s.)
(1.000 μm of ol/mL, 0.300 μm of ol/mL, 0.100 μm of ol/mL, 0.030 μm of ol/mL and 0.010 μm of ol/mL), each concentration
Four parallel samples, every group of experiment is 3 times parallel, and is drawn a conclusion by blank group control.Microplate reader detects each hole OD values, detection
Wavelength 570nm.
3. antitumor activity evaluation
1) cell inhibitory rate calculates：
2)IC50Value calculates
Sample solution concentration logarithm and cell inhibitory rate linear regression calculate sample using software SPSS and press down to the half of cell
Concentration IC processed50Value.(Z/E) -1- (benzofuran -5- bases) -3- aryl -2- (1,2,4- triazol-1-yl) -2- propylene -1- ketone pair
The IC of cancer cell50It is shown in Table 1~2.
Table 1 (Z/E) -1- (benzofuran -5- bases) -3- aryl -2- (1,2,4- triazol-1-yl) -2- propylene -1- ketone
IC50
Table 2 (Z/E) -1- (benzofuran -5- bases) -3- aryl -2- (1,2,4- triazol-1-yl) -2- propylene -1- ketone
IC50
Test result shows (Z/E)-(Z/E) -1- (benzofuran -5- bases) -3- aryl -2- (1,2,4- triazol-1-yl) -
2- propylene -1- ketone is respectively to human cervical carcinoma cell (Hela), and human lung carcinoma cell (A549), human breast cancer cell (MCF-7) has good
Good inhibitory activity, can be used as the application for preparing anticarcinogen.
Claims (7)
1- shown in chemical structural formula I or II 1. (benzofuran -5- bases) -3- aryl -2- (1,2,4- triazol-1-yl) -2- third
Alkene -1- ketone or its salt：
Wherein, R is selected from：Hydrogen, deuterium, C1~C2Alkyl, C3~C4Straight chained alkyl or branched alkyl；X1、X5It is selected from：Hydrogen, deuterium, C1~C2
Alkyl, C3~C4Straight chained alkyl or branched alkyl, hydroxyl, C1~C2Alkoxy, C3~C4Unbranched alkoxy or branched alkoxy,
Fluorine, chlorine, bromine or nitro；X3It is selected from：Hydrogen, deuterium, C1~C2Alkyl, C3~C4Straight chained alkyl or branched alkyl, hydroxyl, C1~C2Alcoxyl
Base, C3~C4Unbranched alkoxy or branched alkoxy, fluorine, chlorine, bromine or nitro；X2、X4It is selected from：Hydrogen, deuterium, C1~C2Alkyl, C3~C4
Straight chained alkyl or branched alkyl or nitro；Its salt is selected from：Hydrochloride, hydrobromate, sulfate, nitrate, phosphate, methylsulphur
Hydrochlorate, benzene sulfonate, tosilate, malate, lactate, succinate or butene dioic acid salt.
2. 1- (benzofuran -5- bases) -3- aryl -2- (1,2,4- triazol-1-yl) -2- propylene -1- described in claim 1
Ketone, it is characterised in that III or IV compound represented of preferred chemical structural formula：
X in formula1~X5Definition it is as described in claim 1.
3. 1- (benzofuran -5- bases) -3- aryl -2- (1,2,4- triazol-1-yl) -2- propylene -1- described in claim 1
Ketone, it is characterised in that V or VI compound represented of preferred chemical structural formula：
X in formula1~X5Definition it is as described in claim 1.
4. 1- (benzofuran -5- bases) -3- aryl -2- (1,2,4- triazol-1-yl) -2- propylene -1- described in claim 1
Ketone, it is characterised in that VII or VIII compound represented of preferred chemical structural formula：
X in formula1~X5Definition it is as described in claim 1.
5. 1- (benzofuran -5- bases) -3- aryl -2- (1,2,4- triazol-1-yls) -2- propylene -1- ketone described in claim 1
It is selected from：1- (7- methoxyl group -2,2- dimethyl -2,3- Dihydrobenzofuranes -5- bases) -3- (4- hydroxy phenyls) -2- (1,2,4- tri-
Azoles -1- bases) -2- propylene -1- ketone, 1- (7- methoxyl group -2,2- dimethyl -2,3- Dihydrobenzofuranes -5- bases) -3- (2- methoxies
Base phenyl) -2- (1,2,4- triazol-1-yls) -2- propylene -1- ketone, 1- (7- methoxyl group -2,2- dimethyl -2,3- dihydrobenzo furans
Mutter -5- bases) -3- (4- fluorophenyls) -2- (1,2,4- triazol-1-yls) -2- propylene -1- ketone, 1- (7- methoxyl group -2,2- dimethyl -
2,3- Dihydrobenzofuranes -5- bases) -3- (2- chlorphenyls) -2- (1,2,4- triazol-1-yls) -2- propylene -1- ketone, 1- (7- methoxies
Base -2,2- dimethyl -2,3- Dihydrobenzofuranes -5- bases) -3- (4- chlorphenyls) -2- (1,2,4- triazol-1-yls) -2- propylene -
1- ketone, 1- (7- methoxyl group -2,2- dimethyl -2,3- Dihydrobenzofuranes -5- bases) -3- (2,4- dichlorophenyl) -2- (1,2,4-
Triazol-1-yl) -2- propylene -1- ketone, 1- (7- methoxyl group -2,2- dimethyl -2,3- Dihydrobenzofuranes -5- bases) -3- (4- bromines
Phenyl) -2- (1,2,4- triazol-1-yls) -2- propylene -1- ketone, 1- (7- methoxyl group -2,2- dimethyl -2,3- dihydrobenzo furans
Mutter -5- bases) -3- (2- nitrobenzophenones) -2- (1,2,4- triazol-1-yls) -2- propylene -1- ketone, 1- (7- methoxyl group -2,2- diformazans
Base -2,3- Dihydrobenzofuranes -5- bases) -3- (3- nitrobenzophenones) -2- (1,2,4- triazol-1-yls) -2- propylene -1- ketone, 1-
(7- methoxyl group -2,2- dimethyl -2,3- Dihydrobenzofuranes -5- bases) -3- (4- nitrobenzophenones) -2- (1,2,4- triazoles -1-
Base) -2- propylene -1- ketone, 1- (7- ethyoxyl -2,2- dimethyl -2,3- Dihydrobenzofuranes -5- bases) -3- (4- aminomethyl phenyls) -
2- (1,2,4- triazol-1-yls) -2- propylene -1- ketone, 1- (7- ethyoxyl -2,2- dimethyl -2,3- Dihydrobenzofuranes -5-
Base) -3- (4- aminomethyl phenyls) -2- (1,2,4- triazol-1-yls) -2- propylene -1- ketone, 1- (dimethyl -2 7- ethyoxyl -2,2-,
3- Dihydrobenzofuranes -5- bases) -3- (2- methoxyphenyls) -2- (1,2,4- triazol-1-yls) -2- propylene -1- ketone, 1- (7- second
Oxygroup -2,2- dimethyl -2,3- Dihydrobenzofuranes -5- bases) -3- (4- fluorophenyls) -2- (1,2,4- triazol-1-yls) -2- third
Alkene -1- ketone, 1- (7- ethyoxyl -2,2- dimethyl -2,3- Dihydrobenzofuranes -5- bases) -3- (2- chlorphenyls) -2- (1,2,4-
Triazol-1-yl) -2- propylene -1- ketone, 1- (7- ethyoxyl -2,2- dimethyl -2,3- Dihydrobenzofuranes -5- bases) -3- (4- chlorine
Phenyl) -2- (1,2,4- triazol-1-yls) -2- propylene -1- ketone, 1- (7- ethyoxyl -2,2- dimethyl -2,3- dihydrobenzo furans
Mutter -5- bases) -3- (2,4- dichlorophenyl) -2- (1,2,4- triazol-1-yl) -2- propylene -1- ketone, 1- (7- ethyoxyls -2,2- bis-
Methyl -2,3- Dihydrobenzofuranes -5- bases) -3- (4- bromophenyls) -2- (1,2,4- triazol-1-yls) -2- propylene -1- ketone, 1-
(7- ethyoxyl -2,2- dimethyl -2,3- Dihydrobenzofuranes -5- bases) -3- (2- nitrobenzophenones) -2- (1,2,4- triazoles -1-
Base) -2- propylene -1- ketone, 1- (7- ethyoxyl -2,2- dimethyl -2,3- Dihydrobenzofuranes -5- bases) -3- (3- nitrobenzophenones) -
2- (1,2,4- triazol-1-yls) -2- propylene -1- ketone, 1- (7- ethyoxyl -2,2- dimethyl -2,3- Dihydrobenzofuranes -5-
Base) -3- (4- nitrobenzophenones) -2- (1,2,4- triazol-1-yls) -2- propylene -1- ketone, 1- (dimethyl -2 7- propoxyl group -2,2-,
3- Dihydrobenzofuranes -5- bases) -3- phenyl -2- (1,2,4- triazol-1-yls) -2- propylene -1- ketone, 1- (7- propoxyl group -2,2-
Dimethyl -2,3- Dihydrobenzofuranes -5- bases) -3- (4- aminomethyl phenyls) -2- (1,2,4- triazol-1-yls) -2- propylene -1- ketone,
1- (7- propoxyl group -2,2- dimethyl -2,3- Dihydrobenzofuranes -5- bases) -3- (2- methoxyphenyls) -2- (1,2,4- triazoles -
1- yls) -2- propylene -1- ketone, 1- (7- propoxyl group -2,2- dimethyl -2,3- Dihydrobenzofuranes -5- bases) -3- (4- fluorophenyls) -
2- (1,2,4- triazol-1-yls) -2- propylene -1- ketone, 1- (7- propoxyl group -2,2- dimethyl -2,3- Dihydrobenzofuranes -5-
Base) -3- (2- chlorphenyls) -2- (1,2,4- triazol-1-yls) -2- propylene -1- ketone, 1- (7- propoxyl group -2,2- dimethyl -2,3-
Dihydrobenzofuranes -5- bases) -3- (4- chlorphenyls) -2- (1,2,4- triazol-1-yls) -2- propylene -1- ketone, 1- (7- propoxyl group -
2,2- dimethyl -2,3- Dihydrobenzofuranes -5- bases) -3- (2,4- dichlorophenyl) -2- (1,2,4- triazol-1-yl) -2- third
Alkene -1- ketone, 1- (7- propoxyl group -2,2- dimethyl -2,3- Dihydrobenzofuranes -5- bases) -3- (4- bromophenyls) -2- (1,2,4-
Triazol-1-yl) -2- propylene -1- ketone, 1- (7- propoxyl group -2,2- dimethyl -2,3- Dihydrobenzofuranes -5- bases) -3- (2- nitre
Base phenyl) -2- (1,2,4- triazol-1-yls) -2- propylene -1- ketone, 1- (7- propoxyl group -2,2- dimethyl -2,3- dihydrobenzo furans
Mutter -5- bases) -3- (3- nitrobenzophenones) -2- (1,2,4- triazol-1-yls) -2- propylene -1- ketone or 1- (7- propoxyl group -2,2- diformazans
Base -2,3- Dihydrobenzofuranes -5- bases) -3- (4- nitrobenzophenones) -2- (1,2,4- triazol-1-yls) -2- propylene -1- ketone.
6. 1- (benzofuran -5- bases) -3- aryl -2- (1,2,4- triazol-1-yls) -2- propylene -1- ketone described in claim 1
Preparation method, it is characterised in that it to prepare reaction equation as follows：
R in formula, X1~X5Definition it is as described in claim 1.
7. 1- (benzofuran -5- bases) -3- aryl -2- (1,2,4- triazol-1-yls)-according to any one of claims 1 to 5
The application of 2- propylene -1- ketone or its salt in preparing anti-human cervical cancer cell or human lung carcinoma cell drug.
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| CN102010405B (en) * | 2010-11-08 | 2012-07-25 | 湖南大学 | 4-(benzofuran-5-yl)-2-benzal aminothiazole and application of 4-(benzofuran-5-base)-2-benzal aminothiazole as antineoplastic agent |
| CN102675303B (en) * | 2011-10-19 | 2014-04-09 | 湖南大学 | 4-alkyl-2-arylamino-5-(1,2,4-triazole-1-group) thiazole and application thereof to preparation of medicaments for resisting cancer |
| CN102942536A (en) * | 2012-12-03 | 2013-02-27 | 湖南大学 | 4-tertiary butyl-5-(1-aryl-2-ethyl nitrate)-2-amido-thiazole with insecticidal activity and preparation method thereof |
| CN103145700B (en) * | 2013-04-01 | 2015-04-01 | 湖南大学 | 2-(2-benzyl hydrazono)-4-(benzofuran-5-yl) thiazole and preparation method and application thereof |
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