CN110229081A - 2,4- dinitrobenzene hydazone derivative and the preparation method and application thereof - Google Patents
2,4- dinitrobenzene hydazone derivative and the preparation method and application thereof Download PDFInfo
- Publication number
- CN110229081A CN110229081A CN201910585002.4A CN201910585002A CN110229081A CN 110229081 A CN110229081 A CN 110229081A CN 201910585002 A CN201910585002 A CN 201910585002A CN 110229081 A CN110229081 A CN 110229081A
- Authority
- CN
- China
- Prior art keywords
- hydroxyl
- ethyoxyl
- methoxyl group
- dihydroxy
- hydroxy
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- WDCYWAQPCXBPJA-UHFFFAOYSA-N 1,3-dinitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC([N+]([O-])=O)=C1 WDCYWAQPCXBPJA-UHFFFAOYSA-N 0.000 title claims abstract description 17
- 238000002360 preparation method Methods 0.000 title claims description 16
- 150000003839 salts Chemical class 0.000 claims abstract description 18
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 claims abstract description 10
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 9
- 229940123424 Neuraminidase inhibitor Drugs 0.000 claims abstract description 4
- 239000002911 sialidase inhibitor Substances 0.000 claims abstract description 4
- 239000000126 substance Substances 0.000 claims abstract 2
- 150000001875 compounds Chemical class 0.000 claims description 21
- 238000006243 chemical reaction Methods 0.000 claims description 8
- GQIVASLYJABIKA-UHFFFAOYSA-N 4-[[(2,4-dinitrophenyl)hydrazinylidene]methyl]phenol Chemical compound [N+](=O)([O-])C1=C(C=CC(=C1)[N+](=O)[O-])NN=CC1=CC=C(C=C1)O GQIVASLYJABIKA-UHFFFAOYSA-N 0.000 claims description 5
- MWOOGOJBHIARFG-UHFFFAOYSA-N vanillin Chemical compound COC1=CC(C=O)=CC=C1O MWOOGOJBHIARFG-UHFFFAOYSA-N 0.000 claims description 3
- FGQOOHJZONJGDT-UHFFFAOYSA-N vanillin Natural products COC1=CC(O)=CC(C=O)=C1 FGQOOHJZONJGDT-UHFFFAOYSA-N 0.000 claims description 3
- 235000012141 vanillin Nutrition 0.000 claims description 3
- 206010022000 influenza Diseases 0.000 claims description 2
- 241000712461 unidentified influenza virus Species 0.000 abstract description 7
- 125000002887 hydroxy group Chemical group [H]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 16
- 235000002639 sodium chloride Nutrition 0.000 description 15
- 239000003795 chemical substances by application Substances 0.000 description 10
- -1 hydrazine class compound Chemical class 0.000 description 10
- 239000003826 tablet Substances 0.000 description 10
- 239000000243 solution Substances 0.000 description 8
- 230000000694 effects Effects 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 102000005348 Neuraminidase Human genes 0.000 description 6
- 108010006232 Neuraminidase Proteins 0.000 description 6
- 238000000034 method Methods 0.000 description 6
- 239000003085 diluting agent Substances 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 230000002401 inhibitory effect Effects 0.000 description 5
- 238000002347 injection Methods 0.000 description 5
- 239000007924 injection Substances 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 4
- 238000005160 1H NMR spectroscopy Methods 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 4
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- 229920002472 Starch Polymers 0.000 description 4
- 239000008103 glucose Substances 0.000 description 4
- 235000001727 glucose Nutrition 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 239000008107 starch Substances 0.000 description 4
- 235000019698 starch Nutrition 0.000 description 4
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 229930195725 Mannitol Natural products 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 3
- 239000011230 binding agent Substances 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 235000019441 ethanol Nutrition 0.000 description 3
- 239000007902 hard capsule Substances 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000000594 mannitol Substances 0.000 description 3
- 235000010355 mannitol Nutrition 0.000 description 3
- 239000007901 soft capsule Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 239000000080 wetting agent Substances 0.000 description 3
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 229920001353 Dextrin Polymers 0.000 description 2
- 239000004375 Dextrin Substances 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical group [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 2
- 239000006184 cosolvent Substances 0.000 description 2
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 2
- 235000019425 dextrin Nutrition 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 230000005284 excitation Effects 0.000 description 2
- 150000007857 hydrazones Chemical class 0.000 description 2
- BQINXKOTJQCISL-GRCPKETISA-N keto-neuraminic acid Chemical compound OC(=O)C(=O)C[C@H](O)[C@@H](N)[C@@H](O)[C@H](O)[C@H](O)CO BQINXKOTJQCISL-GRCPKETISA-N 0.000 description 2
- 239000008297 liquid dosage form Substances 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 239000008108 microcrystalline cellulose Substances 0.000 description 2
- 229940016286 microcrystalline cellulose Drugs 0.000 description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 2
- CERZMXAJYMMUDR-UHFFFAOYSA-N neuraminic acid Natural products NC1C(O)CC(O)(C(O)=O)OC1C(O)C(O)CO CERZMXAJYMMUDR-UHFFFAOYSA-N 0.000 description 2
- 230000003204 osmotic effect Effects 0.000 description 2
- 238000010979 pH adjustment Methods 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000008299 semisolid dosage form Substances 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000007909 solid dosage form Substances 0.000 description 2
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- DWNBOPVKNPVNQG-LURJTMIESA-N (2s)-4-hydroxy-2-(propylamino)butanoic acid Chemical compound CCCN[C@H](C(O)=O)CCO DWNBOPVKNPVNQG-LURJTMIESA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- 239000004925 Acrylic resin Substances 0.000 description 1
- 229920000178 Acrylic resin Polymers 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 229920002785 Croscarmellose sodium Polymers 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- 239000001828 Gelatine Substances 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 239000002262 Schiff base Substances 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- 238000007792 addition Methods 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 230000036592 analgesia Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000000078 anti-malarial effect Effects 0.000 description 1
- 230000000702 anti-platelet effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 239000003430 antimalarial agent Substances 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 150000003934 aromatic aldehydes Chemical class 0.000 description 1
- 150000003935 benzaldehydes Chemical class 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 235000010216 calcium carbonate Nutrition 0.000 description 1
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 1
- 229940095672 calcium sulfate Drugs 0.000 description 1
- 235000011132 calcium sulphate Nutrition 0.000 description 1
- 229960001631 carbomer Drugs 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 239000007910 chewable tablet Substances 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 229960001681 croscarmellose sodium Drugs 0.000 description 1
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 1
- 239000003405 delayed action preparation Substances 0.000 description 1
- 230000000994 depressogenic effect Effects 0.000 description 1
- 235000019700 dicalcium phosphate Nutrition 0.000 description 1
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 description 1
- 239000007919 dispersible tablet Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 239000007938 effervescent tablet Substances 0.000 description 1
- 239000002662 enteric coated tablet Substances 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 239000002532 enzyme inhibitor Substances 0.000 description 1
- 229940125532 enzyme inhibitor Drugs 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 210000001508 eye Anatomy 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 229940012356 eye drops Drugs 0.000 description 1
- 239000010408 film Substances 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 235000012907 honey Nutrition 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- 125000001841 imino group Chemical group [H]N=* 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 239000002608 ionic liquid Substances 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 229940040145 liniment Drugs 0.000 description 1
- 239000000865 liniment Substances 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical compound [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 1
- 239000003595 mist Substances 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 210000000214 mouth Anatomy 0.000 description 1
- UPSFMJHZUCSEHU-JYGUBCOQSA-N n-[(2s,3r,4r,5s,6r)-2-[(2r,3s,4r,5r,6s)-5-acetamido-4-hydroxy-2-(hydroxymethyl)-6-(4-methyl-2-oxochromen-7-yl)oxyoxan-3-yl]oxy-4,5-dihydroxy-6-(hydroxymethyl)oxan-3-yl]acetamide Chemical compound CC(=O)N[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@H]1[C@H](O)[C@@H](NC(C)=O)[C@H](OC=2C=C3OC(=O)C=C(C)C3=CC=2)O[C@@H]1CO UPSFMJHZUCSEHU-JYGUBCOQSA-N 0.000 description 1
- 210000003928 nasal cavity Anatomy 0.000 description 1
- 239000007923 nasal drop Substances 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- HKOOXMFOFWEVGF-UHFFFAOYSA-N phenylhydrazine Chemical compound NNC1=CC=CC=C1 HKOOXMFOFWEVGF-UHFFFAOYSA-N 0.000 description 1
- 229940067157 phenylhydrazine Drugs 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229960000502 poloxamer Drugs 0.000 description 1
- 229920001983 poloxamer Polymers 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- GULVDPYLWVXKGC-UHFFFAOYSA-N quinoxalin-2-ylhydrazine Chemical compound C1=CC=CC2=NC(NN)=CN=C21 GULVDPYLWVXKGC-UHFFFAOYSA-N 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 239000011535 reaction buffer Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 235000015424 sodium Nutrition 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000007940 sugar coated tablet Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- ODLHGICHYURWBS-LKONHMLTSA-N trappsol cyclo Chemical compound CC(O)COC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)COCC(O)C)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1COCC(C)O ODLHGICHYURWBS-LKONHMLTSA-N 0.000 description 1
- 210000001215 vagina Anatomy 0.000 description 1
- 239000000052 vinegar Substances 0.000 description 1
- 235000021419 vinegar Nutrition 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C251/00—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton
- C07C251/72—Hydrazones
- C07C251/86—Hydrazones having doubly-bound carbon atoms of hydrazone groups bound to carbon atoms of six-membered aromatic rings
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Virology (AREA)
- Medicinal Chemistry (AREA)
- Pulmonology (AREA)
- Communicable Diseases (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Molecular Biology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Oncology (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The present invention relates to 2,4- dinitrobenzene hydazone derivative and its pharmaceutically acceptable salt shown in chemical structural formula I, pharmaceutical composition and its preparing the application in influenza virus neuraminidase inhibitor:
Description
Technical field
The present invention relates to a kind of noval chemical compound, preparation method and application, specifically 2,4- dinitrobenzene hydazone derivative, its
Preparation method and its in the application for preparing influenza virus neuraminidase inhibitor.
Background technique
Hydrazone (Hydrazone) class compound is to be obtained by aldehydes or ketones class compound and hydrazine class compound by dehydrating condensation
Schiff base compound contains imino group and time amino groups [Asian Journal of Pharmacy and
Pharmacology,2018,4(2):116-122].Fragrant hydrazone compounds have extensive bioactivity, such as antiviral, anti-
The bioactivity such as depressed, antitumor, antibacterial, anti-inflammatory, anti-malarial, analgesia, anti-platelet aggregation and blood vessel dilatation.
2003, Jarikote etc. [Ultrasonics Sonochemistry, 2003,10 (1): 45-48] was not being added
In the case where catalyst, by reacting phenylhydrazine under ultrasonic radiation with carbonyls, aryl hydrazone compounds have been synthesized:
2010, Ajani etc. [Bioorganic&Medicinal Chemistry, 2010,18 (1): 214-221] description
The cyclohexanone of -2 (1H) -one of 3- diazanyl quinoxaline and 2 substitutions, by microwave irradiation technology have synthesized 2- quinokysalines -3-
Hydazone derivative, and have rated its antibacterial activity:
2014, Oliveira etc. [RSC Advances, 2014,4 (100): 56736-56742] describe organic hydrazine and
Benzaldehyde derivative has synthesized a series of hydrazone compounds by no catalyst and solvent-free mechanochemistry approach:
2015, Parveen etc. [New Journal of Chemistry, 2015,39 (1): 469-481] described water
Hydrazine and substituted aromatic aldehyde are closed, in ionic liquid [Et3NH][HSO4] fragrant double hydazone derivatives have been synthesized under catalyst:
Summary of the invention
The technical problem to be solved by the present invention is to provide a kind of 2,4- dinitrobenzene hydazone derivatives, preparation method, medicine group
Close object and purposes.
To solve technical problem of the invention, the invention provides the following technical scheme:
There is provided a kind of 2,4- dinitrobenzene hydazone derivatives as shown in structural formula I for the first aspect of technical solution of the present invention
And its pharmaceutically acceptable salt:
Wherein, Y is selected from: 2- hydroxyl, 3- hydroxyl, 4- hydroxyl, 2,4- dihydroxy, 3,4- dihydroxy, 2,5- dihydroxy, 3,5-
Dihydroxy, 2,6- dihydroxy, 2- hydroxy-3-methoxy, 2- hydroxyl -4- methoxyl group, 2- hydroxy-5-methyl oxygroup, 2- hydroxyl -6- first
Oxygroup, 3- hydroxyl -2- methoxyl group, 3- hydroxyl -4- methoxyl group, 3- hydroxy-5-methyl oxygroup, 3- hydroxyl -6- methoxyl group, 4- hydroxyl -
2- methoxyl group, 4- hydroxy-3-methoxy, 4- hydroxyl -3,5- dimethoxy, 2- hydroxyl -3- ethyoxyl, 2- hydroxyl -4- ethyoxyl,
2- hydroxyl -5- ethyoxyl, 2- hydroxyl -6- ethyoxyl, 3- hydroxyl -2- ethyoxyl, 3- hydroxyl -4- ethyoxyl, 3- hydroxyl -5- ethoxy
Base, 3- hydroxyl -6- ethyoxyl, 4- hydroxyl -2- ethyoxyl, 4- hydroxyl -3- ethyoxyl, 4- hydroxyl -3,5- diethoxy, 2,3,4-
Trihydroxy or 4- hydroxyl -3,5- dimethyl.
Further, preferred compound is selected from: 4- hydroxy benzaldehyde -2,4- dinitrophenylhydrazone, 3- methoxyl group -4- hydroxyl
Benzaldehyde -2,4- dinitrophenylhydrazone, 3,4- 4-dihydroxy benzaldehyde -2,4- dinitrophenylhydrazone or 2,4- 4-dihydroxy benzaldehyde -2,4-
Dinitrophenylhydrazone.
There is provided the preparation method of 2,4- dinitrobenzene hydazone derivative, features for the second aspect of technical solution of the present invention
It is that its preparation reaction is as follows:
Wherein, Y is selected from: 2- hydroxyl, 3- hydroxyl, 4- hydroxyl, 2,4- dihydroxy, 3,4- dihydroxy, 2,5- dihydroxy, 3,5-
Dihydroxy, 2,6- dihydroxy, 2- hydroxy-3-methoxy, 2- hydroxyl -4- methoxyl group, 2- hydroxy-5-methyl oxygroup, 2- hydroxyl -6- first
Oxygroup, 3- hydroxyl -2- methoxyl group, 3- hydroxyl -4- methoxyl group, 3- hydroxy-5-methyl oxygroup, 3- hydroxyl -6- methoxyl group, 4- hydroxyl -
2- methoxyl group, 4- hydroxy-3-methoxy, 4- hydroxyl -3,5- dimethoxy, 2- hydroxyl -3- ethyoxyl, 2- hydroxyl -4- ethyoxyl,
2- hydroxyl -5- ethyoxyl, 2- hydroxyl -6- ethyoxyl, 3- hydroxyl -2- ethyoxyl, 3- hydroxyl -4- ethyoxyl, 3- hydroxyl -5- ethoxy
Base, 3- hydroxyl -6- ethyoxyl, 4- hydroxyl -2- ethyoxyl, 4- hydroxyl -3- ethyoxyl, 4- hydroxyl -3,5- diethoxy, 2,3,4-
Trihydroxy or 4- hydroxyl -3,5- dimethyl.
The third aspect of technical solution of the present invention, which is to provide, contains compound described in first aspect and its pharmaceutically acceptable
Salt pharmaceutical composition, the pharmaceutical composition contain therapeutically effective amount 2,4- dinitrobenzene hydazone derivative of the invention and its
Pharmaceutically acceptable salt, and optional contain pharmaceutical carrier.Wherein the pharmaceutical carrier refers to the common medicine of pharmaceutical field
Use carrier;The pharmaceutical composition can be prepared according to method well known in the art.It can be by by the compounds of this invention and its pharmaceutically
Acceptable salt is combined with one or more pharmaceutically acceptable solids or liquid excipient and/or adjuvant, is made suitable for people
Or any dosage form that animal uses.The content of the compounds of this invention and its pharmaceutically acceptable salt in its pharmaceutical composition is logical
It is often 0.1%~95% weight percent.
The compounds of this invention and its pharmaceutically acceptable salt can be in a unit containing its pharmaceutical composition
Administration, administration route can be enteron aisle or non-bowel, and such as oral, intravenous injection, intramuscular injection, subcutaneous injection, nasal cavity, oral cavity are viscous
Film, eye, lung and respiratory tract, skin, vagina, rectum etc..
Form of administration can be liquid dosage form, solid dosage forms or semisolid dosage form.Liquid dosage form can be solution (including
True solution and colloidal solution), emulsion (including o/w type, w/o type and emulsion), suspension, injection (including liquid drugs injection, powder-injection
And infusion), eye drops, nasal drop, lotion and liniment etc.;Solid dosage forms can be tablet (including ordinary tablet, enteric coatel tablets, lozenge,
Dispersible tablet, chewable tablets, effervescent tablet, oral disnitegration tablet), capsule (including hard capsule, soft capsule, capsulae enterosolubilis), granule, dissipate
Agent, pellet, dripping pill, suppository, film, patch, the agent of gas (powder) mist, spray etc.;Semisolid dosage form can be ointment, gel
Agent, paste etc..
It is sustained release preparation, control that the compounds of this invention and its pharmaceutically acceptable salt, which can be made ordinary preparation, also be made,
Release formulation, targeting preparation and various particulate delivery systems.
In order to which tablet is made in the compounds of this invention and its pharmaceutically acceptable salt, can be widely used known in this field
Various excipient, including diluent, binder, wetting agent, disintegrating agent, lubricant, glidant.Diluent can be starch,
Dextrin, sucrose, glucose, lactose, mannitol, sorbierite, xylitol, microcrystalline cellulose, calcium sulfate, calcium monohydrogen phosphate, calcium carbonate
Deng;Wetting agent can be water, ethyl alcohol, isopropanol etc.;Adhesive can be starch slurry, dextrin, syrup, honey, glucose solution,
Microcrystalline cellulose, mucialga of arabic gummy, gelatine size, sodium carboxymethylcellulose, methylcellulose, hydroxypropyl methyl cellulose, ethyl
Cellulose, acrylic resin, carbomer, polyvinylpyrrolidone, polyethylene glycol etc.;It is fine that disintegrating agent can be dried starch, crystallite
Tie up element, low-substituted hydroxypropyl cellulose, crosslinked polyvinylpyrrolidone, croscarmellose sodium, sodium carboxymethyl starch, carbon
Sour hydrogen sodium and citric acid, polyoxyethylene sorbitol aliphatic ester, dodecyl sodium sulfate etc.;Lubricant and glidant can be
Talcum powder, silica, stearate, tartaric acid, atoleine, polyethylene glycol etc..
Tablet can also be further made to coating tablet, such as sugar coated tablet, thin membrane coated tablet, enteric coated tablets or double
Synusia and multilayer tablet.
It, can be by effective component the compounds of this invention and its pharmaceutically acceptable in order to which capsule is made in administration unit
Salt is mixed with diluent, glidant, and mixture is placed directly in hard capsule or soft capsule.It can also be by the effective component present inventionization
Close object and its pharmaceutically acceptable salt and particle or pellet first be made with diluent, binder, disintegrating agent, then be placed in hard capsule or
In soft capsule.It is used to prepare the compounds of this invention and its each diluent of pharmaceutically acceptable salt tablet, binder, wetting
Agent, disintegrating agent, glidant kind can also be used for preparing the capsule of the compounds of this invention and its pharmaceutically acceptable salt.
For injection is made in the compounds of this invention and its pharmaceutically acceptable salt, can with water, ethyl alcohol, isopropanol,
Simultaneously appropriate solubilizer commonly used in the art, cosolvent, pH adjustment agent, osmotic pressure is added in propylene glycol or their mixture as solvent
Regulator.Solubilizer or cosolvent can be poloxamer, lecithin, hydroxypropyl-β-cyclodextrin etc.;PH adjustment agent can be phosphorus
Hydrochlorate, acetate, hydrochloric acid, sodium hydroxide etc.;Osmotic pressure regulator can be sodium chloride, mannitol, glucose, phosphate, vinegar
Hydrochlorate etc..Freeze drying powder injection is such as prepared, mannitol, glucose etc. can also be added as proppant.
In addition, if desired, colorant, preservative, fragrance, corrigent or other additions can also be added into pharmaceutical preparation
Agent.
To reach medication purpose, enhance therapeutic effect, drug of the invention or pharmaceutical composition well known can be given with any
The administration of prescription method.
The fourth aspect of technical solution of the present invention is to provide 2,4- dinitrobenzene hydazone derivative of the present invention and its pharmacy
Upper acceptable salt and third aspect described pharmaceutical composition answering in terms of preparing influenza virus neuraminidase inhibitor
With.
Advantageous effects:
2,4- dinitrobenzene hydazone derivative of the invention is a kind of change with influenza neuraminidase inhibitory activity
Close object.
Specific embodiment
Following embodiment is intended to illustrate invention rather than limitation of the invention further.
Embodiment 1
The preparation of 4- hydroxy benzaldehyde -2,4- dinitrophenylhydrazone (A1)
1.0mmol2,4- dinitrophenylhydrazine and 1.05mmol4- hydroxy benzaldehyde are dissolved in 10mL ethyl alcohol, are stirred at room temperature
6h, TLC monitoring reaction.Reaction mixture is filtered, washs filter cake with petroleum ether and ethyl acetate mixtures (1:1), dry
4- hydroxy benzaldehyde -2,4- dinitrophenylhydrazone (A1), red solid, m.p.263~264 DEG C, yield 89.7%;1H NMR
(400MHz, DMSO-d6) δ: 11.82 (s, 1H, NH), 9.94 (s, 1H, OH), 8.98 (d, J=2.5 Hz, 1H, C6H3), 8.34
(dd, J=9.3,2.5 Hz, 1H, C6H3), 8.12 (s, 1H, CH), 7.57 (d, J=8.4 Hz, 2H, C6H4), 7.26 (d, J=
9.3 Hz, 1H, C6H3), 6.83 (d, J=8.4 Hz, 2H, C6H4);13C NMR (100 MHz, DMSO-d6) δ: 160.04,
150.08,144.61,136.89,130.06,129.71,125.12,123.78,123.40,116.90,116.11.
Embodiment 2
The preparation of Vanillin -2,4- dinitrophenylhydrazone (A2)
It prepares according to the method for embodiment 1,1.0mmol2,4- dinitrophenylhydrazine and 1.05mmol3- methoxyl group -4- hydroxyl
Benzaldehyde reacts 6h, obtains Vanillin -2,4- dinitrophenylhydrazone (A2), red solid, m.p.266~267
DEG C, yield 96.1%;1H NMR (400 MHz, DMSO-d6) δ: 11.55 (s, 1H, NH), 9.69 (s, 1H, OH), 8.83 (s, 1H,
CH), 8.54 (d, J=4.2 Hz, 1H, C6H3), 8.32 (d, J=9.6 Hz, 1H, C6H3), 8.06 (dd, J=9.6,4.2 Hz,
1H, C6H3), 7.36 (s, 1H, C6H3), 7.15 (d, J=8.1 Hz, 1H, C6H3), 6.86 (d, J=8.1 Hz, 1H, C6H3),
3.86 (s, 3H, CH3O);13C NMR (100 MHz, DMSO-d6) δ: 150.16,149.65,148.11,144.40,136.53,
129.66,128.93,125.10,123.08,122.61,116.71,115.59,109.56,55.65.
Embodiment 3
The preparation of 3,4- 4-dihydroxy benzaldehyde -2,4- dinitrophenylhydrazone (A3)
It prepares according to the method for embodiment 1,1.0mmol2,4- dinitrophenylhydrazine and 1.05mmol3,4- 4-dihydroxy benzaldehyde
6h is reacted, 3,4- 4-dihydroxy benzaldehyde -2,4- dinitrophenylhydrazone (A3), red solid, m.p.272~273 DEG C, yield are obtained
91.2%;1H NMR (400 MHz, DMSO-d6) δ: 11.52 (s, 1H, NH), 9.58 (s, 1H, OH), 9.28 (s, 1H, OH),
8.85 (s, 1H, CH), 8.51 (d, J=3.0 Hz, 1H, C6H3), 8.36 (d, J=9.6 Hz, 1H, C6H3), 7.98 (dd, J=
9.6,3.0 Hz, 1H, C6H3), 7.24 (s, 1H, C6H3), 7.03 (d, J=8.1 Hz, 1H, C6H3), 6.82 (d, J=8.1 Hz,
1H, C6H3);13C NMR (100 MHz, DMSO-d6) δ: 150.43,148.64,145.79,144.41,136.48,129.74,
128.87,125.12,123.15,120.94,116.41,115.74,113.31.
Embodiment 4
The preparation of 2,4- 4-dihydroxy benzaldehyde -2,4- dinitrophenylhydrazone (A4)
It prepares according to the method for embodiment 1,1.0mmol2,4- dinitrophenylhydrazine and 1.05mmol2,4- 4-dihydroxy benzaldehyde
6h is reacted, 2,4- 4-dihydroxy benzaldehyde -2,4- dinitrophenylhydrazone (A4), red solid, m.p. > 280 DEG C, yield 91.2% are obtained;1H NMR (400 MHz, DMSO-d6) δ: 11.57 (s, 1H, NH), 10.11 (s, 1H, OH), 9.94 (s, 1H, OH), 8.84 (s,
1H, C6H3), 8.79 (s, 1H, CH), 8.31 (d, J=9.6 Hz, 1H, C6H3), 7.93 (d, J=9.6 Hz, 1H, C6H3), 7.63
(d, J=9.2 Hz, 1H, C6H3), 6.35 (s, 1H, C6H3), 6.34 (d, J=9.2Hz, 1H, C6H3);13C NMR (100 MHz,
DMSO-d6) δ: 161.33,158.69,147.69,144.16,136.24,129.65,128.71,128.26,123.14,
116.38,111.51,108.19,102.39.
Embodiment 5
The resisiting influenza virus neuraminidase activity of 2,4- dinitrobenzene hydazone derivative
1. experimental principle
Compound MUNANA is the specific substrate of neuraminidase, the metabolite generated under neuraminic acid enzyme effect
Under 360nm irradiation excitation, 450nm fluorescence can produce, the variation of fluorescence intensity can delicately react neuraminic acid enzyme activity
Property.Enzyme both is from A/PR/8/34 (H1N1) virus stain.
2. experimental method
In enzyme reaction system, a certain concentration sample and influenza virus mind NA are suspended in reaction buffer (pH6.5), add
Enter fluorogenic substrate MUNANA starting reaction system, 37 DEG C are incubated for after forty minutes, and reaction terminating liquid is added to terminate reaction.In excitation wavelength
Under the Parameter Conditions that 360nm and launch wavelength are 450nm, fluorescence intensity level is measured.The fluorescence intensity of reaction system can reflect
The activity of enzyme.Compound can be calculated to the active inhibiting rate of NA according to the reduction amount of fluorescence intensity.
3. test sample: embodiment compound
4. Activity Results
Compound is in reaction system to the inhibiting rate and IC of neuraminidase when 40.0 μ g/mL of detectable concentration50Value is included in
Table 1.
Inhibitory activity and IC of the 1 2,4- dinitrobenzene hydazone derivative of table to neuraminidase H1N150
Compound | Y | Inhibiting rate (%) | IC50(μg/mL) |
A1 | 4-OH | 73.08±8.21 | 18.39±2.91 |
A2 | 4-OH-3-OCH3 | 76.88±4.60 | 17.40±1.49 |
A3 | 3,4-(OH)2 | 41.53±2.60 | - |
A4 | 2,4-(OH)2 | 80.48±2.22 | 13.81±0.80 |
2,4- dinitrobenzene hydazone derivatives have resisiting influenza virus neuraminidase activity, can be used for preparing influenza virus mind
Through propylhomoserin enzyme inhibitor.
Claims (5)
1. 2,4- dinitrobenzene hydazone derivative and its pharmaceutically acceptable salt shown in a kind of chemical structural formula I or II:
Wherein, Y is selected from: 2- hydroxyl, 3- hydroxyl, 4- hydroxyl, 2,4- dihydroxy, 3,4- dihydroxy, 2,5- dihydroxy, 3,5- dihydroxy
Base, 2,6- dihydroxy, 2- hydroxy-3-methoxy, 2- hydroxyl -4- methoxyl group, 2- hydroxy-5-methyl oxygroup, 2- hydroxyl -6- methoxy
Base, 3- hydroxyl -2- methoxyl group, 3- hydroxyl -4- methoxyl group, 3- hydroxy-5-methyl oxygroup, 3- hydroxyl -6- methoxyl group, 4- hydroxyl -2-
Methoxyl group, 4- hydroxy-3-methoxy, 4- hydroxyl -3,5- dimethoxy, 2- hydroxyl -3- ethyoxyl, 2- hydroxyl -4- ethyoxyl, 2-
Hydroxyl -5- ethyoxyl, 2- hydroxyl -6- ethyoxyl, 3- hydroxyl -2- ethyoxyl, 3- hydroxyl -4- ethyoxyl, 3- hydroxyl -5- ethoxy
Base, 3- hydroxyl -6- ethyoxyl, 4- hydroxyl -2- ethyoxyl, 4- hydroxyl -3- ethyoxyl, 4- hydroxyl -3,5- diethoxy, 2,3,4-
Trihydroxy or 4- hydroxyl -3,5- dimethyl.
2. one kind 2,4- dinitrobenzene hydazone derivative and its pharmaceutically acceptable salt are selected from following compounds:
4- hydroxy benzaldehyde -2,4- dinitrophenylhydrazone,
Vanillin -2,4- dinitrophenylhydrazone,
3,4- 4-dihydroxy benzaldehyde -2,4- dinitrophenylhydrazone or
2,4- 4-dihydroxy benzaldehyde -2,4- dinitrophenylhydrazone.
3. the preparation method of 2,4- dinitrobenzene hydazone derivative described in claim 1, which is characterized in that its preparation reaction is such as
Under:
In formula, the definition of Y is as described in claim 1.
4. 2,4- dinitrobenzene hydazone derivative of any of claims 1 or 2 and its pharmaceutically acceptable salt are in preparation influenza
Application in neuraminidase inhibitor.
5. available carrier at least one of a kind of pharmaceutical composition, including claims 1 or 2 compound and pharmaceutics.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201910585002.4A CN110229081B (en) | 2019-07-01 | 2019-07-01 | 2, 4-dinitrophenylhydrazone derivative and preparation method and application thereof |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201910585002.4A CN110229081B (en) | 2019-07-01 | 2019-07-01 | 2, 4-dinitrophenylhydrazone derivative and preparation method and application thereof |
Publications (2)
Publication Number | Publication Date |
---|---|
CN110229081A true CN110229081A (en) | 2019-09-13 |
CN110229081B CN110229081B (en) | 2022-02-08 |
Family
ID=67857913
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201910585002.4A Expired - Fee Related CN110229081B (en) | 2019-07-01 | 2019-07-01 | 2, 4-dinitrophenylhydrazone derivative and preparation method and application thereof |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN110229081B (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN115160180A (en) * | 2022-06-22 | 2022-10-11 | 广东海洋大学 | Green synthesis method of vanillin shrinkage 2, 4-dinitrophenylhydrazone |
Citations (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4670437A (en) * | 1985-09-11 | 1987-06-02 | Eli Lilly And Company | Antiviral pyridazine hydrazones |
UA6147A1 (en) * | 1986-06-09 | 1994-12-29 | Львівський Державний Медичний Інститут | 2-(2',7'-diacetoxy-fluorenylidene-9'-hydrazono)-5-heptylidene-thiazolidone-4 exhibiting anti-influenza action against the influenza a and a-2 virus |
UA6149A1 (en) * | 1986-06-10 | 1994-12-29 | Львівський Державний Медичний Інститут | 2-(2',7'-diacetoxy-fluorenylidene-9'-hydrazono)-5-(n-nitrobenzylidene)-thiazolidone-4 exhibiting antiviral action against the influenza a and a-2 virus and vaccinia virus |
US7341720B2 (en) * | 2005-04-06 | 2008-03-11 | Genzyme Corporation | Targeting of glycoprotein therapeutics |
CN101830854A (en) * | 2009-03-09 | 2010-09-15 | 中国科学院上海药物研究所 | Substituted phenylhydrazones compounds, preparation method and application thereof |
WO2011113060A2 (en) * | 2010-03-12 | 2011-09-15 | Trana Discovery, Inc. | Antiviral compounds and methods of use thereof |
EP2004649B1 (en) * | 2006-03-24 | 2012-07-04 | The Feinstein Institute for Medical Research | Phenolic hydrazone macrophage migration inhibitory factor inhibitors |
CN104024849A (en) * | 2011-08-12 | 2014-09-03 | 生命科技公司 | Apparatuses, methods, computer program products, and kits for hi-throughput glycan analysis |
CN105796545A (en) * | 2016-05-25 | 2016-07-27 | 华中师范大学 | Applications of hydrazone compound in preparing antifungal medicine |
CN107987033A (en) * | 2018-01-05 | 2018-05-04 | 湖南大学 | The application of vanillic aldehyde and its isomers in NA inhibitor is prepared |
-
2019
- 2019-07-01 CN CN201910585002.4A patent/CN110229081B/en not_active Expired - Fee Related
Patent Citations (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4670437A (en) * | 1985-09-11 | 1987-06-02 | Eli Lilly And Company | Antiviral pyridazine hydrazones |
UA6147A1 (en) * | 1986-06-09 | 1994-12-29 | Львівський Державний Медичний Інститут | 2-(2',7'-diacetoxy-fluorenylidene-9'-hydrazono)-5-heptylidene-thiazolidone-4 exhibiting anti-influenza action against the influenza a and a-2 virus |
UA6149A1 (en) * | 1986-06-10 | 1994-12-29 | Львівський Державний Медичний Інститут | 2-(2',7'-diacetoxy-fluorenylidene-9'-hydrazono)-5-(n-nitrobenzylidene)-thiazolidone-4 exhibiting antiviral action against the influenza a and a-2 virus and vaccinia virus |
US7341720B2 (en) * | 2005-04-06 | 2008-03-11 | Genzyme Corporation | Targeting of glycoprotein therapeutics |
EP2004649B1 (en) * | 2006-03-24 | 2012-07-04 | The Feinstein Institute for Medical Research | Phenolic hydrazone macrophage migration inhibitory factor inhibitors |
CN101830854A (en) * | 2009-03-09 | 2010-09-15 | 中国科学院上海药物研究所 | Substituted phenylhydrazones compounds, preparation method and application thereof |
WO2011113060A2 (en) * | 2010-03-12 | 2011-09-15 | Trana Discovery, Inc. | Antiviral compounds and methods of use thereof |
CN104024849A (en) * | 2011-08-12 | 2014-09-03 | 生命科技公司 | Apparatuses, methods, computer program products, and kits for hi-throughput glycan analysis |
CN105796545A (en) * | 2016-05-25 | 2016-07-27 | 华中师范大学 | Applications of hydrazone compound in preparing antifungal medicine |
CN107987033A (en) * | 2018-01-05 | 2018-05-04 | 湖南大学 | The application of vanillic aldehyde and its isomers in NA inhibitor is prepared |
Non-Patent Citations (2)
Title |
---|
CHEMICAL ABSTRACT RN: "RN:1087696-44-3 等", 《STN ON THE WEB REGISTRY数据库》 * |
DANIELLE CRISTINA ZIMMERMANN-FRANCO ETAL: "In vitro and in vivo anti-inflammatory properties of imine resveratrol analogues", 《BIOORGANIC & MEDICINAL CHEMISTRY (2018)》 * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN115160180A (en) * | 2022-06-22 | 2022-10-11 | 广东海洋大学 | Green synthesis method of vanillin shrinkage 2, 4-dinitrophenylhydrazone |
Also Published As
Publication number | Publication date |
---|---|
CN110229081B (en) | 2022-02-08 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN105777664B (en) | Carboxylate of 2 (2 benzyl hydrazono-) thiazole 5 and preparation method thereof and medical usage | |
CN105622558B (en) | Acyl hydrazone derivative of the ring containing benzofuran and preparation method and application | |
CN105693665B (en) | Hydrazone derivative of the ring containing benzofuran and preparation method thereof and medical usage | |
CN108440468A (en) | 2- (benzofuran -5- bases) phenol and its application as anticancer drug | |
CN108503604A (en) | (4- alkyl -5- acyl group -2- thiazoles) hydazone derivative and its medical usage | |
CN107987033A (en) | The application of vanillic aldehyde and its isomers in NA inhibitor is prepared | |
CN110229081A (en) | 2,4- dinitrobenzene hydazone derivative and the preparation method and application thereof | |
CN105541859B (en) | Dihydrofuran and chromanone derivatives and preparation method thereof and medical usage | |
CN107286133B (en) | Application of -5 (the 4H)-thioketones imines of 3- aryl -1,2,4- triazole as NA inhibitor | |
CN108047160A (en) | 2- (2- benzyls hydrazono-) -5- acyl groups thiazoles and its medical usage | |
CN105541591B (en) | 1‑(The aryl phenyl of 4 hydroxyl 3)2 acetone and preparation method and application | |
CN108546254A (en) | 5- (3- phenyl acryloyls) thiazole and the preparation method and application thereof | |
CN108530439A (en) | Furoyl amine derivative and the preparation method and application thereof | |
CN105669589B (en) | 2 (imino group of 5 acyl group thiazole 2) 4 thiazolinones and preparation method and application | |
CN110183349A (en) | Oxalyl hydazone derivative and the preparation method and application thereof | |
CN109053607A (en) | 4- (4- hydroxy phenyl methylene amino) -1,2,4- triazole -5- thioketones and its medical usage | |
CN107118176B (en) | N-(5- benzyl thiazol-2-yl) morpholinyl amide and its medical usage | |
CN109053606A (en) | 4- (4- hydroxy phenyl methylene amino) -1,2,4- triazole -5- thioketones and its application | |
CN107141267B (en) | N- (5- acyl group thiazol-2-yl) amide and the preparation method and application thereof | |
CN111909082B (en) | Pyridine hydrazone derivatives, and preparation method and application thereof | |
CN111100074B (en) | Pyridazine hydrazone derivative and preparation method and application thereof | |
CN110156704A (en) | 1,2,4- triazole sulfide derivative and its crystal structure and application | |
CN108863972A (en) | Oxazole amide derivatives and the preparation method and application thereof | |
CN111909099B (en) | Pyrimidine hydrazone derivatives, and preparation method and application thereof | |
CN109305979A (en) | 4- dimethylaminobenzaldehyde is preparing the application in NA inhibitor |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant | ||
CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20220208 |