CN105622574B - 3- benzimidazolyl-2 radicals (1H)-qualone derivative and its preparation method and application - Google Patents
3- benzimidazolyl-2 radicals (1H)-qualone derivative and its preparation method and application Download PDFInfo
- Publication number
- CN105622574B CN105622574B CN201610078898.3A CN201610078898A CN105622574B CN 105622574 B CN105622574 B CN 105622574B CN 201610078898 A CN201610078898 A CN 201610078898A CN 105622574 B CN105622574 B CN 105622574B
- Authority
- CN
- China
- Prior art keywords
- compound
- quinolinone
- preparation
- reaction
- methyl
- 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.)
- Expired - Fee Related
Links
- 238000002360 preparation method Methods 0.000 title claims abstract description 46
- -1 methoxyl group Chemical group 0.000 claims abstract description 24
- 239000002246 antineoplastic agent Substances 0.000 claims abstract description 21
- 229940041181 antineoplastic drug Drugs 0.000 claims abstract description 20
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 16
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 14
- 239000001257 hydrogen Substances 0.000 claims abstract description 14
- 239000003960 organic solvent Substances 0.000 claims abstract description 13
- 125000001309 chloro group Chemical group Cl* 0.000 claims abstract description 8
- 238000010438 heat treatment Methods 0.000 claims abstract description 5
- 150000001875 compounds Chemical class 0.000 claims description 111
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 48
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 37
- 238000006243 chemical reaction Methods 0.000 claims description 35
- 238000000034 method Methods 0.000 claims description 30
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 24
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 15
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 15
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 10
- 239000002798 polar solvent Substances 0.000 claims description 8
- 150000003839 salts Chemical class 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 239000002904 solvent Substances 0.000 claims description 5
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 4
- 238000009835 boiling Methods 0.000 claims description 4
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 claims description 3
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
- 125000001153 fluoro group Chemical group F* 0.000 claims 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 2
- 239000004480 active ingredient Substances 0.000 claims 1
- 125000003158 alcohol group Chemical group 0.000 claims 1
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 abstract description 13
- 229960002949 fluorouracil Drugs 0.000 abstract description 13
- 230000000694 effects Effects 0.000 abstract description 11
- 231100000419 toxicity Toxicity 0.000 abstract description 8
- 230000001988 toxicity Effects 0.000 abstract description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 abstract description 7
- 150000002431 hydrogen Chemical class 0.000 abstract description 5
- 229910052731 fluorine Inorganic materials 0.000 abstract description 3
- 239000011737 fluorine Substances 0.000 abstract description 3
- 229910052697 platinum Inorganic materials 0.000 abstract description 3
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Substances [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 abstract description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 abstract description 3
- 150000004987 o-phenylenediamines Chemical class 0.000 abstract description 2
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 abstract 1
- 125000001246 bromo group Chemical group Br* 0.000 abstract 1
- 210000004185 liver Anatomy 0.000 abstract 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 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 107
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 28
- 238000005160 1H NMR spectroscopy Methods 0.000 description 28
- 238000012360 testing method Methods 0.000 description 28
- 238000004809 thin layer chromatography Methods 0.000 description 25
- 210000004027 cell Anatomy 0.000 description 24
- 238000001514 detection method Methods 0.000 description 24
- 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 18
- FANCTJAFZSYTIS-IQUVVAJASA-N (1r,3s,5z)-5-[(2e)-2-[(1r,3as,7ar)-7a-methyl-1-[(2r)-4-(phenylsulfonimidoyl)butan-2-yl]-2,3,3a,5,6,7-hexahydro-1h-inden-4-ylidene]ethylidene]-4-methylidenecyclohexane-1,3-diol Chemical compound C([C@@H](C)[C@@H]1[C@]2(CCCC(/[C@@H]2CC1)=C\C=C\1C([C@@H](O)C[C@H](O)C/1)=C)C)CS(=N)(=O)C1=CC=CC=C1 FANCTJAFZSYTIS-IQUVVAJASA-N 0.000 description 15
- VIMMECPCYZXUCI-MIMFYIINSA-N (4s,6r)-6-[(1e)-4,4-bis(4-fluorophenyl)-3-(1-methyltetrazol-5-yl)buta-1,3-dienyl]-4-hydroxyoxan-2-one Chemical compound CN1N=NN=C1C(\C=C\[C@@H]1OC(=O)C[C@@H](O)C1)=C(C=1C=CC(F)=CC=1)C1=CC=C(F)C=C1 VIMMECPCYZXUCI-MIMFYIINSA-N 0.000 description 15
- YLEIFZAVNWDOBM-ZTNXSLBXSA-N ac1l9hc7 Chemical compound C([C@H]12)C[C@@H](C([C@@H](O)CC3)(C)C)[C@@]43C[C@@]14CC[C@@]1(C)[C@@]2(C)C[C@@H]2O[C@]3(O)[C@H](O)C(C)(C)O[C@@H]3[C@@H](C)[C@H]12 YLEIFZAVNWDOBM-ZTNXSLBXSA-N 0.000 description 15
- 239000000047 product Substances 0.000 description 11
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 10
- 229960004316 cisplatin Drugs 0.000 description 10
- 230000002401 inhibitory effect Effects 0.000 description 9
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 7
- FZERHIULMFGESH-UHFFFAOYSA-N N-phenylacetamide Chemical compound CC(=O)NC1=CC=CC=C1 FZERHIULMFGESH-UHFFFAOYSA-N 0.000 description 6
- 206010028980 Neoplasm Diseases 0.000 description 6
- 230000000259 anti-tumor effect Effects 0.000 description 6
- 201000011510 cancer Diseases 0.000 description 6
- 239000000460 chlorine Substances 0.000 description 6
- 229940125904 compound 1 Drugs 0.000 description 6
- 229940125782 compound 2 Drugs 0.000 description 6
- 229940126214 compound 3 Drugs 0.000 description 6
- 238000001816 cooling Methods 0.000 description 6
- 210000005229 liver cell Anatomy 0.000 description 6
- 239000000126 substance Substances 0.000 description 5
- 238000000967 suction filtration Methods 0.000 description 5
- 238000005406 washing Methods 0.000 description 5
- WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 description 4
- NVKJOXRVEKMMHS-UHFFFAOYSA-N 5-nitro-1,2,4-triazol-3-one Chemical compound [O-][N+](=O)C1=NC(=O)N=N1 NVKJOXRVEKMMHS-UHFFFAOYSA-N 0.000 description 4
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical class O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 description 4
- 235000019441 ethanol Nutrition 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical class C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- CQARNQGPINVKMX-UHFFFAOYSA-N 9h-[1,3]dioxolo[4,5-h]quinolin-8-one Chemical compound C1=C2OCOC2=C2NC(=O)C=CC2=C1 CQARNQGPINVKMX-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 229960001413 acetanilide Drugs 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 238000012216 screening Methods 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- DLUPXHPRWLKDHH-UHFFFAOYSA-N 3-(5,6-dimethyl-1H-benzimidazol-2-yl)-1H-quinolin-2-one Chemical compound Cc1cc2nc([nH]c2cc1C)-c1cc2ccccc2[nH]c1=O DLUPXHPRWLKDHH-UHFFFAOYSA-N 0.000 description 2
- HAVFFLLRAIEYMB-UHFFFAOYSA-N 3-(5,6-dimethyl-1H-benzimidazol-2-yl)-6-methoxy-1H-quinolin-2-one Chemical compound CC1=CC2=C(NC(=N2)C=2C(NC3=CC=C(C=C3C=2)OC)=O)C=C1C HAVFFLLRAIEYMB-UHFFFAOYSA-N 0.000 description 2
- IQRAXXWTUBRQQW-UHFFFAOYSA-N 3-(5,6-dimethyl-1H-benzimidazol-2-yl)-6-methyl-1H-quinolin-2-one Chemical compound CC1=CC2=C(NC(=N2)C=2C(NC3=CC=C(C=C3C=2)C)=O)C=C1C IQRAXXWTUBRQQW-UHFFFAOYSA-N 0.000 description 2
- VOECVANYCBHRHG-UHFFFAOYSA-N 3-(6-bromo-1H-benzimidazol-2-yl)-1H-quinolin-2-one Chemical compound BrC1=CC2=C(NC(=N2)C=2C(NC3=CC=CC=C3C=2)=O)C=C1 VOECVANYCBHRHG-UHFFFAOYSA-N 0.000 description 2
- WYEYAIOOXUQKPH-UHFFFAOYSA-N 3-(6-bromo-1H-benzimidazol-2-yl)-6-methoxy-1H-quinolin-2-one Chemical compound BrC1=CC2=C(NC(=N2)C=2C(NC3=CC=C(C=C3C=2)OC)=O)C=C1 WYEYAIOOXUQKPH-UHFFFAOYSA-N 0.000 description 2
- NBCZLJJKAATXFF-UHFFFAOYSA-N 3-(6-bromo-1H-benzimidazol-2-yl)-6-methyl-1H-quinolin-2-one Chemical compound BrC1=CC2=C(NC(=N2)C=2C(NC3=CC=C(C=C3C=2)C)=O)C=C1 NBCZLJJKAATXFF-UHFFFAOYSA-N 0.000 description 2
- DXOHCQPYGGDAGK-UHFFFAOYSA-N 3-(6-chloro-1H-benzimidazol-2-yl)-1H-quinolin-2-one Chemical compound ClC1=CC2=C(NC(=N2)C=2C(NC3=CC=CC=C3C=2)=O)C=C1 DXOHCQPYGGDAGK-UHFFFAOYSA-N 0.000 description 2
- BFPGXSRKBRGGFS-UHFFFAOYSA-N 3-(6-chloro-1H-benzimidazol-2-yl)-6-methoxy-1H-quinolin-2-one Chemical compound ClC1=CC2=C(NC(=N2)C=2C(NC3=CC=C(C=C3C=2)OC)=O)C=C1 BFPGXSRKBRGGFS-UHFFFAOYSA-N 0.000 description 2
- ZHRKACWENXXEIZ-UHFFFAOYSA-N 3-(6-chloro-1H-benzimidazol-2-yl)-6-methyl-1H-quinolin-2-one Chemical compound ClC1=CC2=C(NC(=N2)C=2C(NC3=CC=C(C=C3C=2)C)=O)C=C1 ZHRKACWENXXEIZ-UHFFFAOYSA-N 0.000 description 2
- KFCRELHNXJIWMY-UHFFFAOYSA-N 3-(6-fluoro-1H-benzimidazol-2-yl)-6-methoxy-1H-quinolin-2-one Chemical compound FC1=CC2=C(NC(=N2)C=2C(NC3=CC=C(C=C3C=2)OC)=O)C=C1 KFCRELHNXJIWMY-UHFFFAOYSA-N 0.000 description 2
- WRWRQCPXJPMHHX-UHFFFAOYSA-N 3-(6-fluoro-1H-benzimidazol-2-yl)-6-methyl-1H-quinolin-2-one Chemical compound FC1=CC2=C(NC(=N2)C=2C(NC3=CC=C(C=C3C=2)C)=O)C=C1 WRWRQCPXJPMHHX-UHFFFAOYSA-N 0.000 description 2
- KQONSQGSHCEZDQ-UHFFFAOYSA-N 3-(6-nitro-1H-benzimidazol-2-yl)-1H-quinolin-2-one Chemical compound [N+](=O)([O-])C1=CC2=C(NC(=N2)C=2C(NC3=CC=CC=C3C=2)=O)C=C1 KQONSQGSHCEZDQ-UHFFFAOYSA-N 0.000 description 2
- RYWOXJCRZULBTL-UHFFFAOYSA-N 6-methoxy-3-(6-nitro-1H-benzimidazol-2-yl)-1H-quinolin-2-one Chemical compound [N+](=O)([O-])C1=CC2=C(NC(=N2)C=2C(NC3=CC=C(C=C3C=2)OC)=O)C=C1 RYWOXJCRZULBTL-UHFFFAOYSA-N 0.000 description 2
- BIEAGGCDGUHTAM-UHFFFAOYSA-N 6-methyl-3-(6-nitro-1H-benzimidazol-2-yl)-1H-quinolin-2-one Chemical compound [N+](=O)([O-])C1=CC2=C(NC(=N2)C=2C(NC3=CC=C(C=C3C=2)C)=O)C=C1 BIEAGGCDGUHTAM-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
- 239000005456 alcohol based solvent Substances 0.000 description 2
- 230000003698 anagen phase Effects 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 238000011081 inoculation Methods 0.000 description 2
- 230000031700 light absorption Effects 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical compound N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 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 2
- 239000007787 solid Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- GEYOCULIXLDCMW-UHFFFAOYSA-N 1,2-phenylenediamine Chemical compound NC1=CC=CC=C1N GEYOCULIXLDCMW-UHFFFAOYSA-N 0.000 description 1
- NCSGPOWDKZUREZ-UHFFFAOYSA-N 1-methoxyquinolin-2-one Chemical compound C1=CC=C2C=CC(=O)N(OC)C2=C1 NCSGPOWDKZUREZ-UHFFFAOYSA-N 0.000 description 1
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 1
- KRAPWXIKIAHKAM-UHFFFAOYSA-N 3-(6-fluoro-1H-benzimidazol-2-yl)-1H-quinolin-2-one Chemical compound Fc1ccc2[nH]c(nc2c1)-c1cc2ccccc2[nH]c1=O KRAPWXIKIAHKAM-UHFFFAOYSA-N 0.000 description 1
- IWFHBRFJOHTIPU-UHFFFAOYSA-N 4,5-dichlorobenzene-1,2-diamine Chemical compound NC1=CC(Cl)=C(Cl)C=C1N IWFHBRFJOHTIPU-UHFFFAOYSA-N 0.000 description 1
- SKIUVOVOIJBJPN-UHFFFAOYSA-N 4,5-dimethoxybenzene-1,2-diamine Chemical compound COC1=CC(N)=C(N)C=C1OC SKIUVOVOIJBJPN-UHFFFAOYSA-N 0.000 description 1
- XSZYBMMYQCYIPC-UHFFFAOYSA-N 4,5-dimethyl-1,2-phenylenediamine Chemical compound CC1=CC(N)=C(N)C=C1C XSZYBMMYQCYIPC-UHFFFAOYSA-N 0.000 description 1
- RQWJHUJJBYMJMN-UHFFFAOYSA-N 4-(trifluoromethyl)benzene-1,2-diamine Chemical compound NC1=CC=C(C(F)(F)F)C=C1N RQWJHUJJBYMJMN-UHFFFAOYSA-N 0.000 description 1
- BXIXXXYDDJVHDL-UHFFFAOYSA-N 4-Chloro-ortho-phenylenediamine Chemical compound NC1=CC=C(Cl)C=C1N BXIXXXYDDJVHDL-UHFFFAOYSA-N 0.000 description 1
- WIHHVKUARKTSBU-UHFFFAOYSA-N 4-bromobenzene-1,2-diamine Chemical compound NC1=CC=C(Br)C=C1N WIHHVKUARKTSBU-UHFFFAOYSA-N 0.000 description 1
- KWEWNOOZQVJONF-UHFFFAOYSA-N 4-fluorobenzene-1,2-diamine Chemical compound NC1=CC=C(F)C=C1N KWEWNOOZQVJONF-UHFFFAOYSA-N 0.000 description 1
- RAUWPNXIALNKQM-UHFFFAOYSA-N 4-nitro-1,2-phenylenediamine Chemical compound NC1=CC=C([N+]([O-])=O)C=C1N RAUWPNXIALNKQM-UHFFFAOYSA-N 0.000 description 1
- ZDSUKNAKOLBIPX-UHFFFAOYSA-N 6-fluoro-1h-benzimidazole Chemical compound FC1=CC=C2N=CNC2=C1 ZDSUKNAKOLBIPX-UHFFFAOYSA-N 0.000 description 1
- 101100136092 Drosophila melanogaster peng gene Proteins 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 230000010718 Oxidation Activity Effects 0.000 description 1
- 229910019213 POCl3 Inorganic materials 0.000 description 1
- 102000019259 Succinate Dehydrogenase Human genes 0.000 description 1
- 108010012901 Succinate Dehydrogenase Proteins 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- 235000005811 Viola adunca Nutrition 0.000 description 1
- 240000009038 Viola odorata Species 0.000 description 1
- 235000013487 Viola odorata Nutrition 0.000 description 1
- 235000002254 Viola papilionacea Nutrition 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000003064 anti-oxidating effect Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 244000309466 calf Species 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 238000000006 cell growth inhibition assay Methods 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000004737 colorimetric analysis Methods 0.000 description 1
- 239000006184 cosolvent Substances 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 231100000263 cytotoxicity test Toxicity 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000007877 drug screening Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 230000005918 in vitro anti-tumor Effects 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 201000007270 liver cancer Diseases 0.000 description 1
- 208000014018 liver neoplasm Diseases 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- XVAIDCNLVLTVFM-UHFFFAOYSA-N methacetin Chemical compound COC1=CC=C(NC(C)=O)C=C1 XVAIDCNLVLTVFM-UHFFFAOYSA-N 0.000 description 1
- 210000003470 mitochondria Anatomy 0.000 description 1
- 230000004660 morphological change Effects 0.000 description 1
- CGLCDOZYDURWIG-UHFFFAOYSA-N n-(1,3-benzodioxol-5-yl)acetamide Chemical compound CC(=O)NC1=CC=C2OCOC2=C1 CGLCDOZYDURWIG-UHFFFAOYSA-N 0.000 description 1
- 125000004287 oxazol-2-yl group Chemical group [H]C1=C([H])N=C(*)O1 0.000 description 1
- 125000006237 oxymethylenoxy group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl chloride Substances ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000820 toxicity test Toxicity 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
- C07D491/056—Ortho-condensed systems with two or more oxygen atoms as ring hetero atoms in the oxygen-containing ring
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
Description
Claims (9)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201610078898.3A CN105622574B (en) | 2016-02-04 | 2016-02-04 | 3- benzimidazolyl-2 radicals (1H)-qualone derivative and its preparation method and application |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201610078898.3A CN105622574B (en) | 2016-02-04 | 2016-02-04 | 3- benzimidazolyl-2 radicals (1H)-qualone derivative and its preparation method and application |
Publications (2)
Publication Number | Publication Date |
---|---|
CN105622574A CN105622574A (en) | 2016-06-01 |
CN105622574B true CN105622574B (en) | 2018-12-25 |
Family
ID=56037957
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201610078898.3A Expired - Fee Related CN105622574B (en) | 2016-02-04 | 2016-02-04 | 3- benzimidazolyl-2 radicals (1H)-qualone derivative and its preparation method and application |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN105622574B (en) |
Families Citing this family (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR3055331B1 (en) * | 2016-08-31 | 2020-03-06 | Adpuerivitam | NMDA RECEPTOR MODULATORS, COMPOSITIONS COMPRISING SAME, AND USE OF SUCH COMPOUNDS IN THE TREATMENT OF DISEASES INVOLVING THE CENTRAL NERVOUS SYSTEM |
CN108003150A (en) * | 2016-10-31 | 2018-05-08 | 河南工业大学 | The preparation method and applications of 4- heteroaryl qualone derivatives |
CN109020997B (en) * | 2018-07-05 | 2021-03-02 | 桂林医学院 | 3-benzimidazole-6, 7-piperonyl-2 (1H) -quinolinone-zinc complex and preparation method and application thereof |
CN114716346B (en) * | 2020-12-15 | 2023-07-04 | 广西师范大学 | 4-nitroaniline derivative and application thereof |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6479512B1 (en) * | 1999-10-19 | 2002-11-12 | Merck & Co., Inc. | Tyrosine kinase inhibitors |
CN104817535A (en) * | 2015-03-19 | 2015-08-05 | 广西师范大学 | Quinolinone derivative, and synthetic method and application thereof |
-
2016
- 2016-02-04 CN CN201610078898.3A patent/CN105622574B/en not_active Expired - Fee Related
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6479512B1 (en) * | 1999-10-19 | 2002-11-12 | Merck & Co., Inc. | Tyrosine kinase inhibitors |
CN104817535A (en) * | 2015-03-19 | 2015-08-05 | 广西师范大学 | Quinolinone derivative, and synthetic method and application thereof |
Non-Patent Citations (1)
Title |
---|
A Simple One-Pot Synthesis of New Imidazol-2-yl-1H-quinolin-2-ones from the Direct Reaction of 2-Chloroquinolin-3-carbaldehyde with Aromatic o-Diamines;Rodrigo Abonia et al.;《European Journal of Organic Chemistry》;20091124(第2期);317-325 * |
Also Published As
Publication number | Publication date |
---|---|
CN105622574A (en) | 2016-06-01 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN105622574B (en) | 3- benzimidazolyl-2 radicals (1H)-qualone derivative and its preparation method and application | |
CN109053731B (en) | P-chloro-substituted pyridazinone-structure-containing spiro [ indolizine-pyrazoline ] derivative and preparation method and application thereof | |
CN105153136B (en) | Brefeldin A ester derivative and its preparation and application | |
CN114133390A (en) | Harmine derivative and preparation method and application thereof | |
EP3403651B1 (en) | Isocorydine derivatives, preparation method and use thereof | |
CN104558094B (en) | Saponin(e aglycone derivative, its preparation method and the application in antineoplastic is prepared | |
CN110437156B (en) | Paeonol dihydropyrimidinone derivative, preparation method and application thereof | |
CN105646546B (en) | The position 20 of camptothecins ester derivant and its antitumor application thereof of acid-sensitive type | |
CN104817535A (en) | Quinolinone derivative, and synthetic method and application thereof | |
CN105732576B (en) | The chloro- 3- of 2- (1H- benzimidazolyl-2 radicals-yl)-quinoline preparation methods and application | |
Reddy et al. | A short and highly convergent approach for the synthesis of rutaecarpine derivatives | |
CN109232570B (en) | Pyridazinone structure-containing spiro [ indolizine-pyrazoline ] derivative and preparation method and application thereof | |
CN110183467B (en) | P-methoxyphenyl substituted chromone structure-containing spiro [ indazole-isoxazole ] derivative, and preparation method and application thereof | |
CN106478692A (en) | Copper-nitrate complex and its synthetic method and application with 1 (2 pyridine) 9 benzyl β carboline as part | |
CN107857766B (en) | Synthetic method and application of spiroindole compound based on phenylalanine and polycarbonyl cyclic ketone compound | |
CN110759920A (en) | P-methoxyphenyl substituted spiro [ indazole-pyrazoline ] derivative containing pyrazole structure and preparation method and application thereof | |
CN107857765B (en) | Synthesis method and application of spiroindole compound based on sarcosine and multi-carbonyl cyclic ketone compound | |
CN103044326A (en) | 5-bromo oxoisoaporphine, and synthesis method and application thereof | |
CN103130803B (en) | Oxidized iso-aporphine alkaloid derivative, synthetic method and application | |
CN109232571B (en) | P-methylmercapto-substituted pyridazinone structure-containing spiro [ indolizine-pyrazoline ] derivative and preparation method and application thereof | |
CN109180675B (en) | P-methoxy substituted pyridazinone structure-containing spiro [ indolizine-pyrazoline ] derivative and preparation method and application thereof | |
CN109232572B (en) | P-methyl-substituted pyridazinone-structure-containing spiro [ indolizine-pyrazoline ] derivative and preparation method and application thereof | |
CN109180676B (en) | 3,4, 5-trimethoxy substituted pyridazinone structure-containing spiro [ indolizine-pyrazoline ] derivative and preparation method thereof | |
CN111533700B (en) | 5-substituted uracil derivative and preparation method and application thereof | |
CN109053732B (en) | Para-fluorine substituted pyridazinone structure-containing spiro [ indolizine-pyrazoline ] derivative and preparation method and application thereof |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
CB03 | Change of inventor or designer information |
Inventor after: Zhang Ye Inventor after: Ma Xianli Inventor after: Kuang Wenbin Inventor after: Yu Yancheng Inventor after: Huang Rizhen Inventor before: Zhang Ye Inventor before: Kuang Wenbin Inventor before: Yu Yancheng Inventor before: Huang Rizhen |
|
CB03 | Change of inventor or designer information | ||
TA01 | Transfer of patent application right |
Effective date of registration: 20170208 Address after: 541004 the Guangxi Zhuang Autonomous Region city two Guilin Road No. 109 North Huancheng Applicant after: Guilin Medical College Address before: Xinyi Road Xiufeng District, Guilin city 541001 No. 21 the Guangxi Zhuang Autonomous Region Applicant before: Guilin Teachers Training College |
|
TA01 | Transfer of patent application right | ||
GR01 | Patent grant | ||
GR01 | Patent grant | ||
CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20181225 Termination date: 20200204 |
|
CF01 | Termination of patent right due to non-payment of annual fee |