CN103936770B - Adamantyl picolinamide title complex, intermediate and its preparation method and application - Google Patents
Adamantyl picolinamide title complex, intermediate and its preparation method and application Download PDFInfo
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- -1 Adamantyl picolinamide Chemical compound 0.000 title claims abstract description 49
- 238000002360 preparation method Methods 0.000 title claims abstract description 43
- VLTRZXGMWDSKGL-UHFFFAOYSA-M perchlorate Inorganic materials [O-]Cl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-M 0.000 claims abstract description 17
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 claims abstract description 15
- OUUQCZGPVNCOIJ-UHFFFAOYSA-M Superoxide Chemical compound [O-][O] OUUQCZGPVNCOIJ-UHFFFAOYSA-M 0.000 claims abstract description 13
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 7
- 238000006243 chemical reaction Methods 0.000 claims description 27
- 239000003960 organic solvent Substances 0.000 claims description 26
- JPVYNHNXODAKFH-UHFFFAOYSA-N Cu2+ Chemical group [Cu+2] JPVYNHNXODAKFH-UHFFFAOYSA-N 0.000 claims description 19
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Natural products CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 19
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims description 11
- XLYOFNOQVPJJNP-ZSJDYOACSA-N heavy water Substances [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 claims description 10
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical group CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 9
- 235000015320 potassium carbonate Nutrition 0.000 claims description 8
- 150000001875 compounds Chemical class 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 6
- 230000035484 reaction time Effects 0.000 claims description 6
- 229910021592 Copper(II) chloride Inorganic materials 0.000 claims description 3
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 claims description 3
- LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 claims description 3
- 125000003944 tolyl group Chemical group 0.000 claims description 3
- 230000000694 effects Effects 0.000 abstract description 15
- 238000000034 method Methods 0.000 abstract description 12
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- 229910052751 metal Inorganic materials 0.000 abstract description 8
- 239000002184 metal Substances 0.000 abstract description 8
- 238000006555 catalytic reaction Methods 0.000 abstract description 7
- 239000002253 acid Substances 0.000 abstract description 5
- 150000002500 ions Chemical class 0.000 abstract description 5
- PNGLEYLFMHGIQO-UHFFFAOYSA-M sodium;3-(n-ethyl-3-methoxyanilino)-2-hydroxypropane-1-sulfonate;dihydrate Chemical compound O.O.[Na+].[O-]S(=O)(=O)CC(O)CN(CC)C1=CC=CC(OC)=C1 PNGLEYLFMHGIQO-UHFFFAOYSA-M 0.000 abstract description 5
- 102000019197 Superoxide Dismutase Human genes 0.000 description 20
- 108010012715 Superoxide dismutase Proteins 0.000 description 20
- 229940032362 superoxide dismutase Drugs 0.000 description 19
- 239000000843 powder Substances 0.000 description 12
- 238000012360 testing method Methods 0.000 description 12
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical group CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- PTFCDOFLOPIGGS-UHFFFAOYSA-N Zinc dication Chemical group [Zn+2] PTFCDOFLOPIGGS-UHFFFAOYSA-N 0.000 description 9
- 239000000243 solution Substances 0.000 description 9
- AUNGANRZJHBGPY-SCRDCRAPSA-N Riboflavin Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-SCRDCRAPSA-N 0.000 description 8
- 238000004458 analytical method Methods 0.000 description 8
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- 102000015782 Electron Transport Complex III Human genes 0.000 description 7
- 108010024882 Electron Transport Complex III Proteins 0.000 description 7
- JPXMTWWFLBLUCD-UHFFFAOYSA-N nitro blue tetrazolium(2+) Chemical compound COC1=CC(C=2C=C(OC)C(=CC=2)[N+]=2N(N=C(N=2)C=2C=CC=CC=2)C=2C=CC(=CC=2)[N+]([O-])=O)=CC=C1[N+]1=NC(C=2C=CC=CC=2)=NN1C1=CC=C([N+]([O-])=O)C=C1 JPXMTWWFLBLUCD-UHFFFAOYSA-N 0.000 description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- 238000005160 1H NMR spectroscopy Methods 0.000 description 5
- 239000010949 copper Substances 0.000 description 5
- ZICQBHNGXDOVJF-UHFFFAOYSA-N diamantane Chemical compound C1C2C3CC(C4)CC2C2C4C3CC1C2 ZICQBHNGXDOVJF-UHFFFAOYSA-N 0.000 description 5
- 230000002401 inhibitory effect Effects 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- AUNGANRZJHBGPY-UHFFFAOYSA-N D-Lyxoflavin Natural products OCC(O)C(O)C(O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-UHFFFAOYSA-N 0.000 description 4
- CTENFNNZBMHDDG-UHFFFAOYSA-N Dopamine hydrochloride Chemical compound Cl.NCCC1=CC=C(O)C(O)=C1 CTENFNNZBMHDDG-UHFFFAOYSA-N 0.000 description 4
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 4
- 230000008859 change Effects 0.000 description 4
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- 238000001514 detection method Methods 0.000 description 4
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- 229930182817 methionine Natural products 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 239000002151 riboflavin Substances 0.000 description 4
- 229960002477 riboflavin Drugs 0.000 description 4
- 235000019192 riboflavin Nutrition 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- 210000000170 cell membrane Anatomy 0.000 description 3
- 150000004699 copper complex Chemical class 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 239000012466 permeate Substances 0.000 description 3
- 239000008363 phosphate buffer Substances 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 108091005804 Peptidases Proteins 0.000 description 2
- 239000004365 Protease Substances 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 2
- 229910021607 Silver chloride Inorganic materials 0.000 description 2
- 241000700605 Viruses Species 0.000 description 2
- ORILYTVJVMAKLC-UHFFFAOYSA-N adamantane Chemical group C1C(C2)CC3CC1CC2C3 ORILYTVJVMAKLC-UHFFFAOYSA-N 0.000 description 2
- 238000013019 agitation Methods 0.000 description 2
- DKNWSYNQZKUICI-UHFFFAOYSA-N amantadine Chemical compound C1C(C2)CC3CC2CC1(N)C3 DKNWSYNQZKUICI-UHFFFAOYSA-N 0.000 description 2
- 229960003805 amantadine Drugs 0.000 description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 229910001914 chlorine tetroxide Inorganic materials 0.000 description 2
- 229960000935 dehydrated alcohol Drugs 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 238000002796 luminescence method Methods 0.000 description 2
- 239000012046 mixed solvent Substances 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 238000002390 rotary evaporation Methods 0.000 description 2
- HKZLPVFGJNLROG-UHFFFAOYSA-M silver monochloride Chemical compound [Cl-].[Ag+] HKZLPVFGJNLROG-UHFFFAOYSA-M 0.000 description 2
- 230000003381 solubilizing effect Effects 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 241000712431 Influenza A virus Species 0.000 description 1
- 241001500351 Influenzavirus A Species 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- 206010039966 Senile dementia Diseases 0.000 description 1
- NLTSQKCDESPFGW-WRHSUISWSA-N [IH]=N[C@]1(CC(CCC2CCC3)C4)CC24C3CC1 Chemical compound [IH]=N[C@]1(CC(CCC2CCC3)C4)CC24C3CC1 NLTSQKCDESPFGW-WRHSUISWSA-N 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- JIMXXGFJRDUSRO-UHFFFAOYSA-N adamantane-1-carboxylic acid Chemical compound C1C(C2)CC3CC2CC1(C(=O)O)C3 JIMXXGFJRDUSRO-UHFFFAOYSA-N 0.000 description 1
- 150000001335 aliphatic alkanes Chemical class 0.000 description 1
- WOLHOYHSEKDWQH-UHFFFAOYSA-N amantadine hydrochloride Chemical compound [Cl-].C1C(C2)CC3CC2CC1([NH3+])C3 WOLHOYHSEKDWQH-UHFFFAOYSA-N 0.000 description 1
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000000078 anti-malarial effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 239000003430 antimalarial agent Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 1
- 229910000024 caesium carbonate Inorganic materials 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 150000003943 catecholamines Chemical class 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 238000002484 cyclic voltammetry Methods 0.000 description 1
- 230000006837 decompression Effects 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 230000003291 dopaminomimetic effect Effects 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 229960004756 ethanol Drugs 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 238000005286 illumination Methods 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 238000012417 linear regression Methods 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
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- 239000000203 mixture Substances 0.000 description 1
- 210000001577 neostriatum Anatomy 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000002953 phosphate buffered saline Substances 0.000 description 1
- IBBMAWULFFBRKK-UHFFFAOYSA-N picolinamide Chemical group NC(=O)C1=CC=CC=N1 IBBMAWULFFBRKK-UHFFFAOYSA-N 0.000 description 1
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 235000011181 potassium carbonates Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- 238000004088 simulation Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 239000003115 supporting electrolyte Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- KBLZDCFTQSIIOH-UHFFFAOYSA-M tetrabutylazanium;perchlorate Chemical compound [O-]Cl(=O)(=O)=O.CCCC[N+](CCCC)(CCCC)CCCC KBLZDCFTQSIIOH-UHFFFAOYSA-M 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 238000000870 ultraviolet spectroscopy Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 229940006486 zinc cation Drugs 0.000 description 1
Landscapes
- Pyridine Compounds (AREA)
Abstract
The present invention discloses a kind of adamantyl picolinamide title complex, intermediate and its preparation method and application, the structure of described title complex is such as formula shown in (I) or formula (II), in formula (I), M is divalent metal, and N1, N2 are halogen anion independently of one another; In formula (II), M is divalent metal, and N3 is selected from perchlorate, hexafluorophosphoricacid acid ions or tetrafluoroborate ion. Title complex provided by the invention or the title complex prepared according to method provided by the invention have the activity of excellent catalysis superoxide anion disproportionation.
Description
Technical field
The present invention relates to a kind of adamantyl picolinamide title complex, prepare the preparation method and application of the intermediate of this adamantyl picolinamide title complex, this adamantyl picolinamide title complex and this intermediate.
Background technology
Medical circle generally thinks that free radical is the major cause that human senility and nerve degenerative diseases produce. Modern medicine confirms, the excessive Superoxide anion free radical (O produced in biological oxidation process2��-) disease such as human senility and cancer, cardiovascular and cerebrovascular diseases and amyotrophic lateral sclerosis can be caused. Superoxide-dismutase (SOD) removes O in body2��-Specificity enzyme, be called as " human body street cleaner ", clinical medicine be used for the treatment of the multiple disease such as Alzheimer's disease and tumour, also extensively for skin care product and healthcare products. But natural SOD have extract difficulty, cost height, transformation period short, easily by protease hydrolysis, be difficult to the shortcoming such as permeate through cell membranes and allogenicity, be restricted on clinical treatment is applied.
Therefore, carrying out the research of SOD chemical simulation, O is removed in exploitation2��-Exogenous chemical medicine, be a kind of effective way of the disease that prevention and therapy causes because of SOD inactivation.
Summary of the invention
It is an object of the invention to, in order to overcome the natural SOD of superoxide-dismutase natural in prior art, there is extraction difficulty, cost height, easily by protease hydrolysis, it is difficult to the shortcoming such as permeate through cell membranes and allogenicity, provide a kind of easily preparation, cost is low, efficiently with the SOD analogue enztme with diamantane and picolinamide structure being easy to permeate through cell membranes, i.e. adamantyl picolinamide title complex, provide the preparation method and application of adamantyl picolinamide title complex simultaneously, additionally provide the intermediate and its preparation method of preparing adamantyl picolinamide title complex.
In order to realize above-mentioned purpose, the present invention provides a kind of adamantyl picolinamide title complex, the structure of described title complex such as formula shown in (I) or formula (II),
In formula (I), M is divalent metal, and N1, N2 are halogen anion independently of one another; In formula (II), M is divalent metal, and N3 is selected from perchlorate, hexafluorophosphoricacid acid ions or tetrafluoroborate ion;
Preferably, in formula (I), M is Cu2+Or Zn2+, N1, N2 are selected from Cl independently of one another-Or Br-; In formula (II), M is Cu2+Or Zn2+, N3 is perchlorate;
More preferably, in formula (I), M is Cu2+, N1, N2 are selected from Cl independently of one another-Or Br-, and N1 with N2 is identical; In formula (II), M is Cu2+, N3 is perchlorate;
Further preferably, the title complex of structure shown in formula (I) is the title complex of structure shown in formula (III), and the title complex of structure shown in formula (II) is the title complex of structure shown in formula (IV).
Present invention also offers the intermediate of the adamantyl picolinamide title complex of structure shown in a kind of preparation formula (I) or formula (II), wherein, the structure of described intermediate such as formula shown in (L1),
Present invention also offers the preparation method of the intermediate of the adamantyl picolinamide title complex of structure shown in a kind of preparation formula (L1), wherein, under the existence of carbonate, compound by structure shown in 1-diamantane acyl chlorides and formula (C1) carries out contact reacts in organic solvent;
Preferably, described carbonate is salt of wormwood or sodium carbonate, and described organic solvent is acetonitrile or toluene;
More preferably, described carbonate is salt of wormwood, and described organic solvent is toluene.
Present invention also offers the preparation method of the adamantyl picolinamide title complex of structure shown in a kind of preparation formula (I) or formula (II), wherein, in presence of organic solvent, by the intermediate of structure shown in formula (L1) and [M (N3)2]��6H2O or [(N1) M (N2)] 2H2O carries out complex reaction;
In above-mentioned formula, M is divalent metal, N1 and N2 is halogen anion, and N3 is selected from perchlorate, hexafluorophosphoricacid acid ions or tetrafluoroborate ion;
Preferably, M is Cu2+Or Zn2+, N1, N2 are selected from Cl independently of one another-Or Br-, N3 is perchlorate;
More preferably, M is Cu2+Or Zn2+, N3 is perchlorate, and N1, N2 are selected from Cl independently of one another-Or Br-, and N1 with N2 is identical;
Further preferably, described [(N1) M (N2)] 2H2O is CuCl2��2H2O, described [M (N3)2]��6H2O is Cu (ClO4)2��6H2O��
Present invention also offers above-mentioned adamantyl picolinamide title complex or adamantyl picolinamide title complex prepared by above-mentioned method in the application eliminated in Superoxide radical anion.
Protein engineering research shows that the SOD active centre of ox red corpuscle has and coordinates, by the copper of divalence or zinc cation, the structure formed with nitrogen-atoms, thus inferring that the adamantyl picolinamide title complex of structure shown in formula provided by the invention (I) or formula (II) may have the activity eliminating Superoxide radical anion, shown in same up-to-date style (I) or formula (II), the adamantyl picolinamide title complex of structure has diamantane and pyridine structure. Diamantane a kind of contains 10 carbon atoms and the cage compound of 16 hydrogen atom three volution saturated alkanes, there is attach structure symmetry, good stability, relatively strong parent's fat cross the feature such as film and bio-compatibility. Amantadine and derivative thereof can suppress influenza A virus to wear into suction suction tract epithelial cell, and the nucleic acid of adventitia and releasing virus that stripping removes virus enters host cell; Dopaminergic terminals release Dopamine HCL (DA) in striatum can also be promoted, strengthen the DA of central nervous system and the effect of catecholamine, increase neuronic DA content. Amantadine and derivative thereof as clinical medicine, extensively for treatment and the prevention of the diseases such as influenza virus A type infectious diseases and Parkinson's disease. Pyridine derivatives, the title complex that easy and metal ion assembling is formed has various structure and unique physicochemical property. Thus inferring, title complex provided by the invention may have excellently stability, relatively strong parent's fat and cross film, bio-compatibility so that this title complex likely has the drug effects such as anti-malarial, antitumor, sterilization, anti-inflammatory, hypertension; Pyridine structure makes the method for the adamantyl picolinamide title complex of structure shown in preparation formula (I) or formula (II) comparatively simple simultaneously, and raw material is easy to get.
Other features and advantages of the present invention are described in detail in embodiment part subsequently.
Accompanying drawing explanation
Accompanying drawing is used to provide a further understanding of the present invention, and forms a part for specification sheets, is used from explanation the present invention with embodiment one below, but is not construed as limiting the invention. In the accompanying drawings:
Fig. 1 is that riboflavin-methionine(Met) luminescence method measures complex-catalyzed superoxide anion O2��-The schematic diagram of disproportionation activity;
Fig. 2 is the adamantyl picolinamide complex monocrystal diffractogram of structure shown in formula (III);
Fig. 3 is the adamantyl picolinamide complex monocrystal diffractogram of structure shown in formula (IV);
Fig. 4 is the test result figure of the adamantyl picolinamide title complex of structure and the activity of BeSOD catalysis superoxide anion disproportionation shown in formula (III) and formula (IV);
Fig. 5 is the test result figure of the electrochemical properties of the adamantyl picolinamide title complex of structure shown in formula (III);
Fig. 6 is the test result figure of the electrochemical properties of the adamantyl picolinamide title complex of structure shown in formula (IV).
Embodiment
Hereinafter the specific embodiment of the present invention is described in detail. Should be understood that, embodiment described herein, only for instruction and explanation of the present invention, is not limited to the present invention.
The present invention provides a kind of adamantyl picolinamide title complex, wherein, the structure of described title complex such as formula shown in (I) or formula (II),
In formula (I), M is divalent metal, and N1, N2 are halogen anion independently of one another; In formula (II), M is divalent metal, and N3 is selected from perchlorate, hexafluorophosphoricacid acid ions or tetrafluoroborate ion;
Preferably, in formula (I), M is Cu2+Or Zn2+, N1, N2 are selected from Cl independently of one another-Or Br-; In formula (II), M is Cu2+Or Zn2+, N3 is perchlorate;
More preferably, in formula (I), M is Cu2+, N1, N2 are selected from Cl independently of one another-Or Br-, and N1 with N2 is identical; In formula (II), M is Cu2+, N3 is perchlorate;
Further preferably, the title complex of structure shown in formula (I) is the title complex of structure shown in formula (III), and the title complex of structure shown in formula (II) is the title complex of structure shown in formula (IV).
The present invention also carries the intermediate having encircleed the adamantyl picolinamide title complex of structure shown in a kind of preparation formula (I) or formula (II), it is characterised in that, the structure of described intermediate such as formula shown in (L1),
Present invention also offers the preparation method of the intermediate of the adamantyl picolinamide title complex of structure shown in a kind of preparation formula (L1), it is characterized in that, under the existence of carbonate, compound by structure shown in 1-diamantane acyl chlorides and formula (C1) carries out contact reacts in organic solvent.
According to the present invention, if described organic solvent can solubilizing reaction raw material and with reaction solvent reaction organic solvent. Acetonitrile, N can be enumerated, one or more in dinethylformamide, methyl-sulphoxide and toluene as such reaction solvent. It is preferably toluene. More preferably above-mentioned organic solvent is anhydrous solvent (namely water-content is less than 50ppm).
1-diamantane acyl chlorides can be commercially available product in the present invention, it is also possible to be existing synthesis now use, in order to ensure the receipts rate of contact reacts, it is preferable that 1-diamantane acyl chlorides now synthesizes existing use.
According to the present invention, the carbonate (namely can be dissolved in above-mentioned organic solvent) that described carbonate preferably can be dissolved in reaction system. One or more in sodium carbonate, salt of wormwood and cesium carbonate can be enumerated as such carbonate. It is preferably sodium carbonate or salt of wormwood, it is more preferable to be salt of wormwood.
According to the present invention, being within the scope of suitable pH to ensure the receipts rate of contact reacts to control described contact reacts, relative to 1-diamantane acyl chlorides 1mmol, the consumption of described carbonate is 1-4mmol.
According to the present invention, the consumption of described Compound C 1 and the consumption of organic solvent can change in wide scope. But in order to improve receipts rate, it is preferable that relative to 1-adamantanamine hydrochloride 1mmol, the consumption of described Compound C 1 is 1-3mmol, and the consumption of described organic solvent is 2-20ml.
In the preparation method of above-mentioned intermediate, in order to improve the receipts rate of contact reacts, it is preferable that described contact reacts carries out below 0 DEG C, and the temperature of reaction of described contact reacts is-10-0 DEG C, it is preferable to-3-0 DEG C;
According to the present invention, in order to described contact reacts can be enable fully to carry out, the reaction times of described contact reacts is 3-20h, it is preferable that 10-15h.
Present invention also offers the preparation method of the adamantyl picolinamide title complex of structure shown in a kind of preparation formula (I) or formula (II), wherein, in presence of organic solvent, by the intermediate of structure shown in formula (L1) and [M (N3)2]��6H2O or [(N1) M (N2)] 2H2O carries out complex reaction;
In formula (L1), n is 1-3, it may be preferred that n is 1;
In above-mentioned formula, M is divalent metal, N1 and N2 is halogen anion, and N3 is selected from perchlorate, hexafluorophosphoricacid acid ions or tetrafluoroborate ion;
Preferably, M is Cu2+Or Zn2+, N1, N2 are selected from Cl independently of one another-Or Br-, N3 is perchlorate;
More preferably, M is Cu2+Or Zn2+, N3 is perchlorate, and N1, N2 are selected from Cl independently of one another-Or Br-, and N1 with N2 is identical;
Further preferably, described [(N1) M (N2)] 2H2O is CuCl2��2H2O, described [M (N3)2]��6H2O is Cu (ClO4)2��6H2O��
According to the present invention, if described organic solvent can solubilizing reaction raw material and with reaction solvent reaction organic solvent. Acetonitrile, N can be enumerated, one or more in the alcohol of dinethylformamide, C1-C3 and methyl-sulphoxide as such reaction solvent. It is preferably the alcohol of C1-C3, it is more preferable to be ethanol. Further preferred above-mentioned organic solvent is anhydrous solvent (namely water-content is less than 50ppm).
According to the present invention, described [M (N3)2]��6H2O��[(N1)M(N2)]��2H2The consumption of O can change in wide region. But in order to improve receipts rate, relative to intermediate described in 1mmol, described [M (N3)2]��6H2O or [(N1) M (N2)] 2H2The consumption of O is 0.5-2mmol; In order to improve receipts rate further, it is more preferable to ground, relative to intermediate described in 1mmol, described [(N1) M (N2)] 2H2The consumption of O or (N1) M (N2) is 0.5-1mmol, and the consumption of described organic solvent is 40-250ml.
According to the present invention, the consumption of described organic solvent can change in wide scope. But in order to improve receipts rate, it is preferable that, relative to intermediate described in 1mmol, the consumption of described organic solvent is 20-400ml; In order to improve receipts rate further, relative to intermediate described in 1mmol, the consumption of described organic solvent is 40-250ml.
According to the present invention, in order to improve the speed of response of complex reaction, it may be preferred that described complex reaction carries out under heating, it is preferable that the temperature of reaction of described complex reaction is 40-100 DEG C, it is more preferable to be 40-80 DEG C.
According to the present invention, in order to described complex reaction can be enable fully to carry out, it is preferable that the reaction times of described complex reaction is 1-6h, it is more preferable to be 2-3h.
Adamantyl picolinamide title complex prepared by the method described in above-mentioned adamantyl picolinamide title complex or upper item that present invention also offers is in the application eliminated in Superoxide radical anion.
Hereinafter will be described the present invention by embodiment, but the present invention is not limited in following embodiment.
The medicine used in following examples, test case and solvent: riboflavin and methionine(Met) are purchased from my fourth reagent (China) company limited; Nitro blue tetrazolium (NBT) is purchased from Sa grace chemical technology (Shanghai) company limited; Other reagent is purchased from Chemical Reagent Co., Ltd., Sinopharm Group.
Testing method in following examples and test case is: ultimate analysis carries out with the use of Germany elemental analyser VarioELICHNanalyzer, examination of infrared spectrum carries out with the use of Japan Shimadzu Fourier transformation infrared spectrometer IRPrestige-21, single crystal diffraction test is undertaken by Germany BrukerAXS single crystal diffractometer Smol/LARTAPEX II, visible-ultraviolet test is undertaken by Japan's Shimadzu ultraviolet-visible pectrophotometer UV-2450 photometer, electrochemical properties test is undertaken by CHI-440a type electrochemical workstation, core magnetic tester is undertaken by Germany's BrukerAV300 nuclear magnetic resonance analyser.
Preparation example 1
The preparation of 1-diamantane acyl chlorides:
In 250mL round-bottomed flask, add 1-adamantanecarboxylic acid solid 10.0mmol and dry toluene solvent 60mL successively, magnetic agitation is slowly dripped after dissolving and is added thionyl chloride 15-40mL, back flow reaction 8 hours at 80 DEG C, being cooled to 20 DEG C, rotary evaporation is except desolventizing, then repeats 3 times and add 10mL dry toluene, rotary evaporation, except desolventizing and excessive thionyl chloride, obtains faint yellow crystalline powder.
Embodiment 1-1
The preparation of the intermediate of structure shown in formula (L1):
In 100mL round-bottomed flask, under 0 DEG C of condition, add 1-diamantane acyl chlorides 5.0mmol and 25mL dry toluene successively, after magnetic agitation is dissolved, add 10mmol Anhydrous potassium carbonate, slower dripping adds PA 6.3mmol, reacts 12 hours under condition of ice bath, filtering, decompression rotates distilled and obtains light yellow thick product 1.154g except after desolventizing. Thick product carries out recrystallization with ethyl acetate and ether mixed solvent, obtains white powder. At ethyl acetate and sherwood oil mixed solvent (v/v=1:3) recrystallization, obtaining white powder 0.873g, receipts rate is 68%. Its detection data are as follows.
White powder is carried out ultimate analysis, and result is C16H20N2O:C, 75.12%; N, 10.87%; H, 7.68%, calculated value: C, 74.97%; N, 10.93%; H, 7.86%, illustrate that detected value and calculated value match;1HNMR(CDCl3,300MHz):��(ppm):8.69(s,1H,NH),8.35-8.38(d,1H,Py),8.241(d,1H,Py),7.78(m,1H,Py),7.08(m,1H,Py),2.11(d,3H,CH),2.00(d,6H,CH2),1.76(m,6H,CH2); IR (KBrdisc, cm-1):3284,3056,2901,2846,1666,1528,1438,1291,1232,1169,1079,790��
Embodiment 1-2
The preparation of the intermediate of structure shown in formula (L1):
Carrying out according to the method for embodiment 1-1, institute is 10mmol the difference is that PA, obtains white powder, and receipts rate is 67%.
White powder is carried out ultimate analysis, and result is C16H20N2O:C, 75.12%; N, 10.87%; H, 7.68%, calculated value: C, 74.97%; N, 10.93%; H, 7.86%, illustrate that detected value and calculated value match;1HNMR(CDCl3,300MHz):��(ppm):8.69(s,1H,NH),8.35-8.38(d,1H,Py),8.241(d,1H,Py),7.78(m,1H,Py),7.08(m,1H,Py),2.11(d,3H,CH),2.00(d,6H,CH2),1.76(m,6H,CH2); IR (KBrdisc, cm-1):3284,3056,2901,2846,1666,1528,1438,1291,1232,1169,1079,790��
Embodiment 1-3
The preparation of the intermediate of structure shown in formula (L1):
Carrying out according to the method for embodiment 1-1, institute is 15mmol the difference is that PA, obtains white powder, and receipts rate is 68%. Its detection data are as follows.
White powder is carried out ultimate analysis, and result is C16H20N2O:C, 75.12%; N, 10.87%; H, 7.68%, calculated value: C, 74.97%; N, 10.93%; H, 7.86%, illustrate that detected value and calculated value match;1HNMR(CDCl3,300MHz):��(ppm):8.69(s,1H,NH),8.35-8.38(d,1H,Py),8.241(d,1H,Py),7.78(m,1H,Py),7.08(m,1H,Py),2.11(d,3H,CH),2.00(d,6H,CH2),1.76(m,6H,CH2); IR (KBrdisc, cm-1):3284,3056,2901,2846,1666,1528,1438,1291,1232,1169,1079,790��
Embodiment 1-4
The preparation of the intermediate of structure shown in formula (L1):
Carrying out according to the method for embodiment 1-1, institute is 5mmol the difference is that salt of wormwood, obtains white powder, and receipts rate is 65%. Its detection data are as follows.
White powder is carried out ultimate analysis, and result is C16H20N2O:C, 75.12%; N, 10.87%; H, 7.68%, calculated value: C, 74.97%; N, 10.93%; H, 7.86%, illustrate that detected value and calculated value match;1HNMR(CDCl3,300MHz):��(ppm):8.69(s,1H,NH),8.35-8.38(d,1H,Py),8.241(d,1H,Py),7.78(m,1H,Py),7.08(m,1H,Py),2.11(d,3H,CH),2.00(d,6H,CH2),1.76(m,6H,CH2); IR (KBrdisc, cm-1):3284,3056,2901,2846,1666,1528,1438,1291,1232,1169,1079,790��
Embodiment 1-5
The preparation of the intermediate of structure shown in formula (L1):
Carrying out according to the method for embodiment 1-1, institute is 18mmol the difference is that salt of wormwood, obtains white powder, and receipts rate is 66%. Its detection data are as follows.
White powder is carried out ultimate analysis, and result is C16H20N2O:C, 75.12%; N, 10.87%; H, 7.68%, calculated value: C, 74.97%; N, 10.93%; H, 7.86%, illustrate that detected value and calculated value match;1HNMR(CDCl3,300MHz):��(ppm):8.69(s,1H,NH),8.35-8.38(d,1H,Py),8.241(d,1H,Py),7.78(m,1H,Py),7.08(m,1H,Py),2.11(d,3H,CH),2.00(d,6H,CH2),1.76(m,6H,CH2); IR (KBrdisc, cm-1):3284,3056,2901,2846,1666,1528,1438,1291,1232,1169,1079,790��
Embodiment 2
The preparation of title complex shown in formula (III):
In 100ml round-bottomed flask, add 0.017gCuCl successively2��2H2O (0.1mmol), (2-pyridine)-1-diamantane acid amides 0.051g (0.2mmol) and 40mL dehydrated alcohol, after 20 DEG C of lower magnetic force stirring and dissolving, back flow reaction 2 hours at 85 DEG C, obtain deep green settled solution, it is cooled to 20 DEG C, place at filtrate 20 DEG C after filtering, slowly volatilization obtained deep green prism-shaped crystal after 3 days, and receipts rate is 52%.
Above-mentioned deep green prism-shaped crystal is carried out ultimate analysis, and result is C32H40N4O2Cl2Cu:C, 63.15%; N, 6.06%; H, 8.91%; Calculated value: C, 63.30%; N, 6.23%; H, 8.66%, illustrate that detected value and calculated value match; IR (KBrdisc, cm-1):2903,2843,1625,1518,1473,1230,781��
Title complex III is carried out single crystal diffraction, result is as shown in Figure 2, as shown in Figure 2, title complex III is mononuclear copper complex, O on 1 upper carbonyl of bivalent cupric ion and two N, Cl and two diamantane carries out coordinating the title complex being formed and having 5 coordinate bonds, and two adamantane structures are centrosymmetric distribution about bivalent cupric ion simultaneously.
Embodiment 3
The preparation of title complex shown in formula (IV):
In 100ml round-bottomed flask, add 0.037gCu (ClO successively4)2��6H2O (0.1mmol), (2-pyridine)-1-diamantane acid amides 0.051g (0.2mmol) and 50mL dehydrated alcohol, after 20 DEG C of lower magnetic force stirring and dissolving, back flow reaction 2 hours at 85 DEG C, obtain mazarine settled solution, it is cooled to 20 DEG C, placing at filtrate 20 DEG C after filtering, slowly volatilization obtained light green prism-shaped crystal after 2 days, and receipts rate is 66%.
Above-mentioned light green prism-shaped crystal is carried out ultimate analysis, and result is C32H40N4O10Cl2Cu:C, 49.39%; N, 7.08%; H, 5.40%; Calculated value: C, 49.58%; N, 7.23%; H, 5.20%, illustrate that detected value and calculated value match; IR (KBrdisc, cm-1):3295,2909,2851,1623,1533,1485,1147,1095,1047,781,621��
Title complex IV is carried out single crystal diffraction, result is as shown in Figure 3, as shown in Figure 3, title complex IV is mononuclear copper complex, O on the upper carbonyl of 1 of bivalent cupric ion and two N and two diamantane carries out coordinating the title complex being formed and having 4 coordinate bonds, and two adamantane structures are centrosymmetric distribution about bivalent cupric ion simultaneously.
Test case 1
Riboflavin-methionine(Met) luminescence method measures complex-catalyzed superoxide anion O2��-The principle of disproportionation activity as shown in Figure 1, when there are not the stand-in of SOD or SOD in the solution, O2The Superoxide radical anion O that under existing, riboflavin and methionine(Met) produce2��-, main O2��-Can react with nitro blue tetrazolium NBT and generate blue compound (in ultraviolet-visible spectrophotometer ��maxCan be detected under=560nm). When solution having SOD or stand-in exist, O2��-Will part catalyzed generation H2O2And O2, the amount generating compound of wearing in one's hair by the blue first moon with NBT reaction just reduces, and therefore can be measured SOD and stand-in catalysis O over time by ��=560nm place absorbancy2��-The activity of disproportionation. Specific experiment method is as follows:
Prepare, with redistilled water, the 0.05mol/L phosphate buffer soln that pH is 7.8, and it is that solvent prepares 8.25 �� 10 respectively taking phosphate buffer soln-5Mol/L riboflavin, the methionine(Met) of 0.25mol/L, 1.15 �� 10-3The NBT of mol/L. In the SOD or stand-in determination of activity of various different concns, get above riboflavin successively, methionine(Met) and each 1mL of NBT solution, mix with the SOD of different concns or stand-in, being diluted to 25mL with phosphate buffered saline buffer, the thermostatic bath lucifuge that then mixed solution puts into 25 �� 0.1 DEG C is put into thermostat container after being incubated 10 minutes and is carried out illumination. Took out the absorbance A that 3mL solution Japan Shimadzu ultraviolet-visible pectrophotometer UV-2450 photometer (doing blank with phosphate buffer soln) measures solution under 560nm wavelength every 0.5 minute in 3.5 minutes. Under measuring, by riboflavin-methionine(Met) method, the title complex different concns obtained, absorbancy is over time, data linear regression fit absorbancy under finite concentration changed in time obtains a straight line, gained straight slope, i.e. the changing value �� A/ �� t of unit time absorbancy. When SOD in solution or stand-in concentration are zero, the �� A/ �� t obtained is (�� A/ �� t) 0, measuring, when the concentration of SOD in solution or stand-in is mol/L, the �� A/ �� t that obtains is (�� A/ �� t) m, obtains SOD or the stand-in inhibiting rate percentage ratio under this concentration by following formula.
Taking title complex concentration as X-coordinate, inhibiting rate is ordinate zou, obtains the concentration that inhibiting rate is 50% title complex, namely draws the SOD reactivity parameter IC of title complex III and title complex IV50, i.e. the concentration of an activity unit, the IC of stand-in50It is worth more little, represents that activity is more high.
Measure the activity of natural ox erythrocyte superoxide dismutase (BeSOD), title complex III and title complex IV catalysis Superoxide radical anion disproportionation according to the method described above. As shown in Figure 4, it is possible to from the change curve of inhibiting rate with Different Complex concentration, the concentration of title complex, i.e. IC when showing that inhibiting rate is 50%50Value. By comparing IC50Value judges the activity of title complex, IC50It is worth more little then expression title complex activity more high.
The IC of BeSOD50It is 0.04 ��m of ol/L, the IC of title complex III50It is the IC of 0.16 ��m of ol/L and title complex IV50It is 0.15 ��m of ol/L, thus illustrates that title complex provided by the invention has the activity of higher catalysis Superoxide radical anion disproportionation.
Test case 2
The redox-potential of title complex III and title complex IV utilizes cyclic voltammetry to measure at CHI-440a type electrochemical workstation, use three-electrode system, platinum wire electrode is as supporting electrode, and glass-carbon electrode is as working electrode, and silver/silver chloride electrode is as reference electrode. Title complex III and title complex IV N, N '-dimethyl methane amide makes solvent, and concentration is that the tetrabutylammonium perchlorate of 0.1mol/L is as supporting electrolyte. All tests carry out in room temperature all under nitrogen protection, and sweep velocity is 100mVS-1. The Electrochemical results of title complex III is as shown in Figure 4: Epc is 0.133V and Epa is 0.324V, and its half-wave potential is 0.229V; The Electrochemical results of title complex IV is as shown in Figure 5: Epc is 0.089V and Epa is 0.452V, and its half-wave potential is 0.271V. The half-wave potential of title complex III-IV is in catalysis superoxide anion disproportionation-0.36V-0.69V(vsAg/AgCl) in potential range, so chemically the known copper complex III-IV in thermodynamics aspect has the activity of catalysis superoxide anion disproportionation.
Below the preferred embodiment of the present invention is described in detail; but, the detail that the present invention is not limited in above-mentioned enforcement mode, within the scope of the technical conceive of the present invention; the technical scheme of the present invention can being carried out multiple simple variant, these simple variant all belong to protection scope of the present invention. It should be noted that in addition, each concrete technology feature described in above-mentioned embodiment, when not contradiction, it is possible to combined by any suitable mode, in order to avoid unnecessary repetition, various possible array mode is illustrated by the present invention no longer separately.
In addition, can also carrying out arbitrary combination between the various different enforcement mode of the present invention, as long as it does not run counter to the thought of the present invention, it should be considered as content disclosed in this invention equally.
Claims (19)
1. an adamantyl picolinamide title complex, it is characterised in that, the structure of described title complex such as formula shown in (I) or formula (II),
In formula (I), M is Cu2+, N1, N2 are halogen anion independently of one another; In formula (II), M is Cu2+, N3 is perchlorate.
2. adamantyl picolinamide title complex according to claim 1, wherein, in formula (I), N1, N2 are selected from Cl independently of one another-Or Br-��
3. adamantyl picolinamide title complex according to claim 2, wherein, in formula (I), N1, N2 are selected from Cl independently of one another-Or Br-, and N1 with N2 is identical.
4. adamantyl picolinamide title complex according to claim 3, wherein, the title complex of structure shown in formula (I) is the title complex of structure shown in formula (III),
5. the preparation method of the intermediate of the adamantyl picolinamide title complex of structure shown in a formula (L1), it is characterized in that, under the existence of carbonate, compound by structure shown in 1-diamantane acyl chlorides and formula (C1) carries out contact reacts in organic solvent
Wherein, described carbonate is salt of wormwood, and described organic solvent is toluene.
6. preparation method according to claim 5, wherein, relative to 1-diamantane acyl chlorides 1mmol, the consumption of described Compound C 1 is 1-3mmol, and the consumption of described organic solvent is 2-20ml, and the consumption of described carbonate is 1-4mmol.
7. preparation method according to claim 5 or 6, wherein, the temperature of reaction of described contact reacts is-10-0 DEG C; The reaction times of described contact reacts is 3-20h.
8. preparation method according to claim 7, wherein, the temperature of reaction of described contact reacts is-3-0 DEG C; The reaction times of described contact reacts is 10-15h.
9. the preparation method of the adamantyl picolinamide title complex of structure shown in a formula according to claim 1 (I) or formula (II), it is characterized in that, in presence of organic solvent, by the intermediate of structure shown in formula according to claim 5 (L1) and [M (N3)2]��6H2O or [(N1) M (N2)] 2H2O carries out complex reaction;
In above-mentioned formula, M is Cu2+, N1 and N2 is halogen anion, and N3 is perchlorate; Described organic solvent is ethanol.
10. preparation method according to claim 9, wherein, N1, N2 are selected from Cl independently of one another-Or Br-��
11. preparation methods according to claim 10, wherein, N1, N2 are selected from Cl independently of one another-Or Br-, and N1 with N2 is identical.
12. preparation methods according to claim 11, wherein, described [(N1) M (N2)] 2H2O is CuCl2��2H2O��
13. according to preparation method described in any one in claim 9-12, wherein, relative to intermediate described in 1mmol, and described [M (N3)2]��6H2O or [(N1) M (N2)] 2H2The consumption of O is 0.5-2mmol, and the consumption that described organic solvent is is 20-400ml.
14. according to preparation method described in any one in claim 13, wherein, relative to intermediate described in 1mmol, and described [(N1) M (N2)] 2H2The consumption of O or (N1) M (N2) is 0.5-1mmol, and the consumption of described organic solvent is 40-250ml.
15. according to preparation method described in any one in claim 9-12, and wherein, the temperature of reaction of described complex reaction is 40-100 DEG C.
16. preparation methods according to claim 15, wherein, the temperature of reaction of described complex reaction is 40-80 DEG C.
17. according to preparation method described in any one in claim 9-12, and wherein, the reaction times of described complex reaction is 1-6h.
18. preparation methods according to claim 17, wherein, the reaction times of described complex reaction is 2-3h.
The application of 19. adamantyl picolinamide title complexs according to claim 1 in the preparation of the medicine for eliminating Superoxide radical anion.
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1230111A (en) * | 1996-07-08 | 1999-09-29 | 盖尔德马研究及发展公司 | Apoptosis inducing adamantyl derivatives and their usage as anti-cancer agents |
| JP2004284994A (en) * | 2003-03-24 | 2004-10-14 | Sumitomo Chem Co Ltd | New copper complex containing adamantane structure |
| CN102105437A (en) * | 2008-07-25 | 2011-06-22 | H.隆德贝克有限公司 | Adamantyl diamide derivatives and uses of same |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1230111A (en) * | 1996-07-08 | 1999-09-29 | 盖尔德马研究及发展公司 | Apoptosis inducing adamantyl derivatives and their usage as anti-cancer agents |
| JP2004284994A (en) * | 2003-03-24 | 2004-10-14 | Sumitomo Chem Co Ltd | New copper complex containing adamantane structure |
| CN102105437A (en) * | 2008-07-25 | 2011-06-22 | H.隆德贝克有限公司 | Adamantyl diamide derivatives and uses of same |
Non-Patent Citations (3)
| Title |
|---|
| Noncovalent interactions between classical supramolecular synthons in solution: Hydrogen bonding in hindered 2-acylaminopyridine/2-pyridone associates;B. Os´miałowski;《Journal of Molecular Structure》;20111109;第1018卷;第84-87页 * |
| owski et al..Self-Organization of 2-Acylaminopyridines in the Solid State and in Solution.《J. Phys. Chem. A》.2010,第114卷第10421-10426页. * |
| SYNTHESIS AND ANTIAGGREGATION ACTIVITY OF 1-ADAMANTOYLAMINOPYRIDINES;V.A. Ermokhin et al.;《Pharmaceutical Chemistry Journal》;20080430;第42卷(第4期);第175-176页 * |
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