CN105968127A - Azacyclic transition metal zinc complex containing multiple coordination sites, and preparation method and application of azacyclic transition metal zinc complex - Google Patents
Azacyclic transition metal zinc complex containing multiple coordination sites, and preparation method and application of azacyclic transition metal zinc complex Download PDFInfo
- Publication number
- CN105968127A CN105968127A CN201610555494.9A CN201610555494A CN105968127A CN 105968127 A CN105968127 A CN 105968127A CN 201610555494 A CN201610555494 A CN 201610555494A CN 105968127 A CN105968127 A CN 105968127A
- Authority
- CN
- China
- Prior art keywords
- transition metal
- solution
- azacyclo
- bta
- methyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 239000011701 zinc Substances 0.000 title claims abstract description 75
- 229910052723 transition metal Inorganic materials 0.000 title claims abstract description 51
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 title claims abstract description 29
- 229910052725 zinc Inorganic materials 0.000 title claims abstract description 29
- 238000002360 preparation method Methods 0.000 title claims abstract description 23
- 150000003624 transition metals Chemical class 0.000 title abstract description 13
- 102000004139 alpha-Amylases Human genes 0.000 claims abstract description 23
- 108090000637 alpha-Amylases Proteins 0.000 claims abstract description 23
- 229940024171 alpha-amylase Drugs 0.000 claims abstract description 23
- -1 transition metal salt Chemical class 0.000 claims abstract description 19
- 230000002218 hypoglycaemic effect Effects 0.000 claims abstract description 13
- 239000003814 drug Substances 0.000 claims abstract description 12
- IQUVMOWIZMLZIA-VOTSOKGWSA-N 6-[(e)-2-phenylethenyl]pyrimidine-2,4,5-triamine Chemical compound NC1=NC(N)=C(N)C(\C=C\C=2C=CC=CC=2)=N1 IQUVMOWIZMLZIA-VOTSOKGWSA-N 0.000 claims abstract description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical class OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 48
- 239000000243 solution Substances 0.000 claims description 47
- 239000003446 ligand Substances 0.000 claims description 31
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 30
- ZNNZYHKDIALBAK-UHFFFAOYSA-M potassium thiocyanate Chemical compound [K+].[S-]C#N ZNNZYHKDIALBAK-UHFFFAOYSA-M 0.000 claims description 21
- 239000013078 crystal Substances 0.000 claims description 20
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 18
- 239000000203 mixture Substances 0.000 claims description 15
- 239000011259 mixed solution Substances 0.000 claims description 14
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 13
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 12
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 9
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims description 9
- 238000000034 method Methods 0.000 claims description 9
- 239000012467 final product Substances 0.000 claims description 8
- 239000002904 solvent Substances 0.000 claims description 8
- 239000000706 filtrate Substances 0.000 claims description 7
- 238000010438 heat treatment Methods 0.000 claims description 7
- 239000012043 crude product Substances 0.000 claims description 6
- 238000001556 precipitation Methods 0.000 claims description 6
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims description 6
- 230000001629 suppression Effects 0.000 claims description 5
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 claims description 4
- ONDPHDOFVYQSGI-UHFFFAOYSA-N zinc nitrate Chemical compound [Zn+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O ONDPHDOFVYQSGI-UHFFFAOYSA-N 0.000 claims description 4
- 229910006124 SOCl2 Inorganic materials 0.000 claims description 3
- MOFINMJRLYEONQ-UHFFFAOYSA-N [N].C=1C=CNC=1 Chemical class [N].C=1C=CNC=1 MOFINMJRLYEONQ-UHFFFAOYSA-N 0.000 claims description 3
- ZOIORXHNWRGPMV-UHFFFAOYSA-N acetic acid;zinc Chemical compound [Zn].CC(O)=O.CC(O)=O ZOIORXHNWRGPMV-UHFFFAOYSA-N 0.000 claims description 3
- 238000001816 cooling Methods 0.000 claims description 3
- 238000001914 filtration Methods 0.000 claims description 3
- 239000000047 product Substances 0.000 claims description 3
- 238000001953 recrystallisation Methods 0.000 claims description 3
- 239000007787 solid Substances 0.000 claims description 3
- 238000003756 stirring Methods 0.000 claims description 3
- 239000004246 zinc acetate Substances 0.000 claims description 3
- 239000011592 zinc chloride Substances 0.000 claims description 2
- 235000005074 zinc chloride Nutrition 0.000 claims description 2
- NWONKYPBYAMBJT-UHFFFAOYSA-L zinc sulfate Chemical group [Zn+2].[O-]S([O-])(=O)=O NWONKYPBYAMBJT-UHFFFAOYSA-L 0.000 claims description 2
- 229960001763 zinc sulfate Drugs 0.000 claims description 2
- 229910000368 zinc sulfate Inorganic materials 0.000 claims description 2
- MLVWCBYTEFCFSG-UHFFFAOYSA-L zinc;dithiocyanate Chemical compound [Zn+2].[S-]C#N.[S-]C#N MLVWCBYTEFCFSG-UHFFFAOYSA-L 0.000 claims 1
- 230000002401 inhibitory effect Effects 0.000 abstract description 10
- 206010012601 diabetes mellitus Diseases 0.000 abstract description 6
- XUFXOAAUWZOOIT-SXARVLRPSA-N (2R,3R,4R,5S,6R)-5-[[(2R,3R,4R,5S,6R)-5-[[(2R,3R,4S,5S,6R)-3,4-dihydroxy-6-methyl-5-[[(1S,4R,5S,6S)-4,5,6-trihydroxy-3-(hydroxymethyl)-1-cyclohex-2-enyl]amino]-2-oxanyl]oxy]-3,4-dihydroxy-6-(hydroxymethyl)-2-oxanyl]oxy]-6-(hydroxymethyl)oxane-2,3,4-triol Chemical compound O([C@H]1O[C@H](CO)[C@H]([C@@H]([C@H]1O)O)O[C@H]1O[C@@H]([C@H]([C@H](O)[C@H]1O)N[C@@H]1[C@@H]([C@@H](O)[C@H](O)C(CO)=C1)O)C)[C@@H]1[C@@H](CO)O[C@@H](O)[C@H](O)[C@H]1O XUFXOAAUWZOOIT-SXARVLRPSA-N 0.000 abstract description 5
- 229960002632 acarbose Drugs 0.000 abstract description 5
- XUFXOAAUWZOOIT-UHFFFAOYSA-N acarviostatin I01 Natural products OC1C(O)C(NC2C(C(O)C(O)C(CO)=C2)O)C(C)OC1OC(C(C1O)O)C(CO)OC1OC1C(CO)OC(O)C(O)C1O XUFXOAAUWZOOIT-UHFFFAOYSA-N 0.000 abstract description 5
- 229940079593 drug Drugs 0.000 abstract description 4
- 239000003472 antidiabetic agent Substances 0.000 abstract 1
- 229940126904 hypoglycaemic agent Drugs 0.000 abstract 1
- 150000001875 compounds Chemical class 0.000 description 14
- 238000012360 testing method Methods 0.000 description 12
- 229920002472 Starch Polymers 0.000 description 6
- 239000008280 blood Substances 0.000 description 6
- 210000004369 blood Anatomy 0.000 description 6
- 239000003153 chemical reaction reagent Substances 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 6
- 235000019698 starch Nutrition 0.000 description 6
- 239000008107 starch Substances 0.000 description 6
- 239000007788 liquid Substances 0.000 description 5
- 239000000470 constituent Substances 0.000 description 4
- 229910017464 nitrogen compound Inorganic materials 0.000 description 4
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000002329 infrared spectrum Methods 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- DTMHTVJOHYTUHE-UHFFFAOYSA-N thiocyanogen Chemical compound N#CSSC#N DTMHTVJOHYTUHE-UHFFFAOYSA-N 0.000 description 3
- WDMUXYQIMRDWRC-UHFFFAOYSA-N 2-hydroxy-3,4-dinitrobenzoic acid Chemical class OC(=O)C1=CC=C([N+]([O-])=O)C([N+]([O-])=O)=C1O WDMUXYQIMRDWRC-UHFFFAOYSA-N 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 229940088598 enzyme Drugs 0.000 description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- 201000001421 hyperglycemia Diseases 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 108010059892 Cellulase Proteins 0.000 description 1
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 206010018473 Glycosuria Diseases 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 244000208060 Lawsonia inermis Species 0.000 description 1
- 238000002441 X-ray diffraction Methods 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 230000005260 alpha ray Effects 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 150000003851 azoles Chemical class 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 229910052804 chromium Inorganic materials 0.000 description 1
- 239000011651 chromium Substances 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 238000002447 crystallographic data Methods 0.000 description 1
- 238000006356 dehydrogenation reaction Methods 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000000378 dietary effect Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000007877 drug screening Methods 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 210000001508 eye Anatomy 0.000 description 1
- 229910002804 graphite Inorganic materials 0.000 description 1
- 239000010439 graphite Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 210000002216 heart Anatomy 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 210000004153 islets of langerhan Anatomy 0.000 description 1
- 238000005304 joining Methods 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 235000012054 meals Nutrition 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 229940127017 oral antidiabetic Drugs 0.000 description 1
- 239000003538 oral antidiabetic agent Substances 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000000135 prohibitive effect Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 229910052720 vanadium Inorganic materials 0.000 description 1
- GPPXJZIENCGNKB-UHFFFAOYSA-N vanadium Chemical compound [V]#[V] GPPXJZIENCGNKB-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F3/00—Compounds containing elements of Groups 2 or 12 of the Periodic Table
- C07F3/06—Zinc compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F3/00—Compounds containing elements of Groups 2 or 12 of the Periodic Table
- C07F3/003—Compounds containing elements of Groups 2 or 12 of the Periodic Table without C-Metal linkages
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses an azacyclic transition metal zinc complex containing multiple coordination sites, and a preparation method and application of the azacyclic transition metal zinc complex. The azacyclic transition metal zinc complex is a 1-(benzotriazole-1-methyl)-1-(2-ethyl imidazole) zinc complex, and has a molecular formula of [Zn (SCN) 2(C12H13N5)2]. The azacyclic transition metal zinc complex, namely, the 1-(benzotriazole-1-methyl)-1-(2-ethyl imidazole) zinc complex provided by the invention has a higher inhibiting effect for alpha-amylase, and the inhibiting effect of the 1-(benzotriazole-1-methyl)-1-(2-ethyl imidazole) zinc complex is much higher than that of singly-used 1-(benzotriazole-1-methyl)-1-(2-ethyl imidazole) or transition metal salt for the alpha-amylase and is higher than that of commonly-used hypoglycemic agent acarbose for the alpha-amylase. Therefore, the azacyclic transition metal zinc complex is proved to have a good hypoglycemic effect so as to be effectively used for preparing medicines for treating diabetes mellitus, and is an innovation in the aspect of medicines for treating the diabetes mellitus.
Description
Technical field
The present invention relates to a kind of azacyclo-transition metal Zn complex containing multiple coordination sites, preparation method and application, belong to medicine
Technical field.
Background technology
Diabetes are a kind of metabolic diseases being characterized with hyperglycemia.Long-standing hyperglycemia during diabetes, is easily caused each
Plant tissue, particularly eye, kidney, heart, blood vessel, neural chronic lesion and dysfunction.At present, the whole world trouble of diabetes
Sick rate is in the rapid increase phase, and China has become as the country that diabetics in the world is most.According to relevant report, crowd
In the middle of many diabeticss, type 2 diabetes mellitus patient has accounted for 90%-95%, and owing to its pathogenic factor is hidden, their early stage
The reasons such as symptom is inconspicuous, and caused complication is many and serious, type 2 diabetes mellitus has become as the main disease threatening human health
One of sick.
The method taked for the treatment of type 2 diabetes mellitus at present mainly has: oral antidiabetic drug, insulin injection, pancreas transplantation hands
The methods such as art, motor adjustment, dietary adjustments.But due to these Therapeutic Method have that blood sugar lowering after the meal is slow, type 2 diabetes mellitus is to islets of langerhans
The strong stress resistance of element, hypoglycemic effect is inconspicuous and the shortcoming such as blood sugar lowering cost prohibitive, and therefore these Therapeutic Method cannot preferably be expired
The blood sugar lowering of foot patient needs.At present, with enzyme or receptor, the drug screening as target spot has become the critical path finding new drug.α-shallow lake
Powder enzyme (α-amylase) is a kind of Endoglucanases, can hydrolyze the α-Isosorbide-5-Nitrae-glucoside bond in starch molecule, by starch
Degrade step by step.Therefore under α-amylase existence condition, add soluble starch and test sample, dropped by α-amylase by measuring
The amount solving the reducing sugar generated evaluates the activity of test sample, i.e. uses the external inhibitory action to α-amylase to evaluate some medicines
The hypoglycemic activity of thing, is a kind of common method of testing.
Heterocyclic nitrogen compound has the strongest coordination function, and this compound can be with a lot of stable joining of transition metal generating structure
Compound；Emulative can occupy the binding site of carbohydrate as hypoglycemic medicine, postpone substrate hydrolysis thus reach blood sugar lowering
Effect.It addition, also there are some researches show, some transition metal such as copper, zinc, chromium, vanadium etc. also have good hypoglycemic activity.
The coordination compound of zinc also result in the concern of vast researcher as the research of hypoglycemic medicine in recent years.But due to transition metal
Large dose oral administration can produce toxic action to human body, and using merely asymmetric heterocyclic nitrogen compound hypoglycemic effect is not to manage very much
The reason such as think.Therefore asymmetric heterocyclic nitrogen compound and transition metal are reacted and make coordination compound just to become a solution above-mentioned
One effective way of problem.
Summary of the invention
In order to solve the problems referred to above, it is an object of the invention to provide a kind of azacyclo-transition metal Zn complex containing multiple coordination sites,
Preparation method and application, this coordination compound preparation method is simple, has good blood sugar reducing function.
To achieve these goals, the technical solution adopted in the present invention is:
A kind of azacyclo-transition metal Zn complex containing multiple coordination sites, described azacyclo-transition metal Zn complex is 1-(benzene
And triazole-1-methyl)-1-(2-ethyl imidazol(e)) Zn complex, molecular formula is [Zn (SCN)2(C12H13N5)2]；Wherein, C12H13N5
For ligand 1-(BTA-1-methyl)-1-(2-ethyl imidazol(e)), molecular structural formula is:
The preparation method of described ligand 1-(BTA-1-methyl)-1-(2-ethyl imidazol(e)), comprises the following steps:
(1) 11.9g BTA, 30ml water and 30ml formaldehyde being mixed, heated and stirred makes solid dissolve, at 80 DEG C of bars
Heating in water bath 1h under part, cooling, it is filtrated to get product as white needles, obtains white crystal by re-crystallizing in ethyl acetate, be hydroxyl
Methyl benzotriazazole；
(2) methylol BTA 7.4g is added in single port bottle, drip 25ml SOCl2, mix and blend after completion of dropwise addition
30min, 80 DEG C of backflow 3h；The SOCl of excess is boiled off with Rotary Evaporators2, obtain white crystal, be chloromethyl benzo three nitrogen
Azoles；
(3) take 2-ethyl imidazol(e) 40mmol, be dissolved in 20ml DMSO, add the NaOH 80mmol pulverized, be heated to
60 DEG C, add 40mmol chloromethyl BTA, 60 DEG C of heating in water bath 1h, be cooled to room temperature, pour in 100g frozen water,
, there is precipitation, sucking filtration in stirring, and precipitation washes with water 3 times, obtains crude product；
(4) crude product recrystallization in ethyl acetate, obtains lacteous crystal, is ligand 1-(BTA-1-methyl)-1-
(2-ethyl imidazol(e)).
The preparation method of a kind of azacyclo-transition metal Zn complex containing multiple coordination sites, comprises the following steps:
(1) accurately weigh transition metal zinc salt 0.02-0.04mmol, be dissolved in 4-6ml solvent, obtain zinc solution；
(2) accurately weigh ligand 1-(BTA-1-methyl)-1-(2-ethyl imidazol(e)) 0.02-0.03mmol, be dissolved in
In 4-6ml solvent, obtain ligand solution；
(3) accurately weigh 0.02-0.03mmol KSCN, be dissolved in 1-2ml water, obtain KSCN solution；And by KSCN
Solution adds in zinc solution, obtains mixed solution；
(4) ligand solution is added in mixed solution, mix homogeneously, filter, filtrate solubilizer to 14-18ml, quiet under room temperature
Put, to separating out colourless rectangle crystal, to obtain final product.
Described transition metal zinc salt is zinc sulfate, zinc acetate, zinc nitrate or zinc chloride.
The solvent of step (1), (2) and (4) be in water, methanol, ethanol, dimethyl sulfoxide, acetonitrile one or both
Mixture.
Preferably, the preparation method of the described azacyclo-transition metal Zn complex containing multiple coordination sites, comprise the following steps:
(1) Zn (Ac) is accurately weighed20.02mmol, is dissolved in 4ml methanol, obtains zinc solution；
(2) accurately weigh ligand 1-(BTA-1-methyl)-1-(2-ethyl imidazol(e)) 0.02mmol, be dissolved in 4ml
In methanol, obtain ligand solution；
(3) accurately weigh 0.02mmol KSCN, be dissolved in 1ml water, obtain KSCN solution；And by KSCN solution
Add in zinc solution, obtain mixed solution；
(4) ligand solution is added in mixed solution, mix homogeneously, to filter, filtrate adds methanol to 14ml, left at room temperature,
To separating out colourless rectangle crystal, to obtain final product.
The application in terms of suppression α-amylase of a kind of azacyclo-transition metal Zn complex containing multiple coordination sites.
The application in terms of preparing hypoglycemic medicine of a kind of azacyclo-transition metal Zn complex containing multiple coordination sites.
Beneficial effect of the present invention
1, the present invention is using 1-(BTA-1-methyl)-1-(2-ethyl imidazol(e)) as part, using zinc as transition metal,
Prepare azacyclo-transition metal Zn complex, efficiently solve asymmetric heterocyclic nitrogen compound as part, with transition metal zinc
Combination problem.
2, the azacyclo-transition metal Zn complex that prepared by the present invention, i.e. 1-(BTA-1-methyl)-1-(2-ethyl miaow
Azoles) Zn complex, α-amylase is had stronger inhibitory action, is significantly larger than used alone 1-(BTA-1-methyl)
-1-(2-ethyl imidazol(e)) or the transition metal salt inhibitory action to α-amylase, be also better than conventional hypoglycemic medicine acarbose.
This shows, the azacyclo-transition metal Zn complex of the present invention has good blood sugar reducing function, can be effectively used for preparation treatment glycosuria
Medicine, is the innovation on treatment diabetes medicament.
3, the preparation method of the present invention is simple and convenient to operate, and production cost is low, it is easy to technology is promoted, and has good society
And economic benefit.
Accompanying drawing explanation
Fig. 1 is coordination compound [Zn (SCN)2(C12H13N5)2] construction unit figure.
Fig. 2 is coordination compound [Zn (SCN)2(C12H13N5)2] accumulation graph.
Detailed description of the invention
Below in conjunction with embodiment, the detailed description of the invention of the present invention is described in further detail.
Embodiment 1
The preparation method of ligand 1 of the present invention-(BTA-1-methyl)-1-(2-ethyl imidazol(e)), comprises the following steps:
(1) 11.9g BTA, 30ml water and 30ml formaldehyde being mixed, heated and stirred makes solid dissolve, at 80 DEG C of bars
Heating in water bath 1h under part, cooling, it is filtrated to get product as white needles, obtains white crystal by re-crystallizing in ethyl acetate, be hydroxyl
Methyl benzotriazazole；
(2) methylol BTA 7.4g is added in single port bottle, drip 25ml SOCl2, mix and blend after completion of dropwise addition
30min, 80 DEG C of backflow 3h；The SOCl of excess is boiled off with Rotary Evaporators2, obtain white crystal, be chloromethyl benzo three nitrogen
Azoles；
(3) take 2-ethyl imidazol(e) 40mmol, be dissolved in 20ml dimethyl sulfoxide (DMSO), add the NaOH pulverized
80mmol, is heated to 60 DEG C, adds 40mmol chloromethyl BTA, 60 DEG C of heating in water bath 1h, is cooled to room temperature,
Pour in 100g frozen water, stirring, precipitation, sucking filtration occur, precipitation washes with water 3 times, obtains crude product；
(4) crude product recrystallization in ethyl acetate, obtains lacteous crystal, is ligand 1-(BTA-1-methyl)-1-
(2-ethyl imidazol(e)).
Prepared ligand 1-(BTA-1-methyl)-1-(2-ethyl imidazol(e)) constituent content is according to C12H13N5Meter (%),
Theoretical value (%): C 63.41；H 5.77；N 30.82；Experiment value (%): C 63.21；H 5.82；N 30.97.Infrared light
Spectrum (cm-1, KBr): 3503 (s), 3236 (m), 3141 (m), 3115 (m), 3092 (w), 2976 (m), 2177
(w), 1927 (w), 1662 (m), 1614 (w), 1531 (w), 1496 (s), 1457 (s), 1431 (m), 1386
(m), 1362 (m), 1269 (s), 1237 (m), 1165 (s), 1103 (w), 1075 (s), 1009 (m), 967
(m), 923 (w), 785 (w), 746 (s), 603 (w), 538 (w).
Embodiment 2
The preparation method of a kind of azacyclo-transition metal Zn complex containing multiple coordination sites, comprises the following steps:
(1) zinc acetate [Zn (Ac) is accurately weighed2] 0.02mmol, it is dissolved in 4ml methanol, obtains zinc solution；
(2) accurately weigh ligand 1-(BTA-1-methyl)-1-(2-ethyl imidazol(e)) 0.02mmol, be dissolved in 4ml
In methanol, obtain ligand solution；
(3) accurately weigh 0.02mmol KSCN, be dissolved in 1ml water, obtain KSCN solution；And by KSCN solution
Add in zinc solution, obtain mixed solution；
(4) ligand solution is added in mixed solution, mix homogeneously, to filter, filtrate adds methanol to 14ml, left at room temperature,
To separating out colourless rectangle crystal, to obtain final product.
Experiment condition and the result of the X-ray single crystal diffraction structure of coordination compound of the present invention are as follows:
Select the preferable single crystal samples of crystal form, Rigaku Saturn 724CCD diffractometer carries out x-ray diffraction experiment, adopts
With the Mo-k alpha ray position (λ=0.71073A) through graphite monochromator monochromatization as diffraction light sources, receive with ω-2 θ scan mode
Collection point diffraction.Crystal structure uses direct method to solve, and extends by Fourier techniques, is modified by anisotropy, finally
Using complete matrix method of least square, be corrected according to observable diffraction data and variable element, all data are through Lp factor school
Just.Solving whole non-hydrogen atom coordinate with direct method, hydrogen atom coordinate is obtained by difference Founcr synthetic method, and structural parameters are by entirely
Matrix least square method optimizes, and dehydrogenation atom uses outside isotropic thermal parameter, and other atom all uses anisotropic thermal parametric method,
All of calculating all uses SHELX 97 program.
The mono-crystalline structures of prepared azacyclo-transition metal Zn complex see Fig. 1,2, this coordination compound belongs to anorthic system, P-1
Space group, cell parameter a isB isC isα is 82.339 °, and β is 82.783 °,
γ is 70.940 °.Constituent content is according to C26H26N12S2Zn counts (%), theoretical value (%): C 49.09；H 4.12；N 26.43；
Experiment value (%): C 49.37；H 4.10；N 26.70.Infrared spectrum (cm-1, KBr): 3435 (w), 3122 (m),
2981 (w), 2940 (w), 2073 (s), 1613 (w), 1547 (m), 1496 (s), 1481 (s), 1378 (m),
1347 (m), 1263 (s), 1180 (s), 1154 (s), 1081 (s), 1054 (w), 964 (m), 751 (s), 654
(w), 509 (w).
Embodiment 3
The preparation method of a kind of azacyclo-transition metal Zn complex containing multiple coordination sites, comprises the following steps:
(1) ZnSO is accurately weighed40.03mmol, is dissolved in 5ml water, obtains zinc solution；
(2) accurately weigh ligand 1-(BTA-1-methyl)-1-(2-ethyl imidazol(e)) 0.03mmol, be dissolved in 5ml
In methanol, obtain ligand solution；
(3) accurately weigh 0.03mmol KSCN, be dissolved in 2ml water, obtain KSCN solution；And by KSCN solution
Add in zinc solution, obtain mixed solution；
(4) ligand solution is added in mixed solution, mix homogeneously, to filter, filtrate adds ethanol to 16ml, left at room temperature,
To separating out colourless rectangle crystal, to obtain final product.
The mono-crystalline structures of prepared azacyclo-transition metal Zn complex see Fig. 1,2, this coordination compound belongs to anorthic system, P-1
Space group, cell parameter a isB isC isα is 82.339 °, and β is 82.783 °,
γ is 70.940 °.Constituent content is according to C26H26N12S2Zn counts (%), theoretical value (%): C 49.09；H 4.12；N 26.43；
Experiment value (%): C 49.37；H 4.10；N 26.70.Infrared spectrum (cm-1, KBr): 3435 (w), 3122 (m),
2981 (w), 2940 (w), 2073 (s), 1613 (w), 1547 (m), 1496 (s), 1481 (s), 1378 (m),
1347 (m), 1263 (s), 1180 (s), 1154 (s), 1081 (s), 1054 (w), 964 (m), 751 (s), 654
(w), 509 (w).
Embodiment 4
The preparation method of a kind of azacyclo-transition metal Zn complex containing multiple coordination sites, comprises the following steps:
(1) ZnCl is accurately weighed20.04mmol, is dissolved in 6ml methanol, obtains zinc solution；
(2) accurately weigh ligand 1-(BTA-1-methyl)-1-(2-ethyl imidazol(e)) 0.03mmol, be dissolved in 6ml
In methanol, obtain ligand solution；
(3) accurately weigh 0.03mmol KSCN, be dissolved in 2ml water, obtain KSCN solution；And by KSCN solution
Add in zinc solution, obtain mixed solution；
(4) ligand solution is added in mixed solution, mix homogeneously, to filter, filtrate adds acetonitrile to 18ml, left at room temperature,
To separating out colourless rectangle crystal, to obtain final product.
The mono-crystalline structures of prepared azacyclo-transition metal Zn complex see Fig. 1,2, this coordination compound belongs to anorthic system, P-1
Space group, cell parameter a isB isC isα is 82.339 °, and β is 82.783 °,
γ is 70.940 °.Constituent content is according to C26H26N12S2Zn counts (%), theoretical value (%): C 49.09；H 4.12；N 26.43；
Experiment value (%): C 49.37；H 4.10；N 26.70.Infrared spectrum (cm-1, KBr): 3435 (w), 3122 (m),
2981 (w), 2940 (w), 2073 (s), 1613 (w), 1547 (m), 1496 (s), 1481 (s), 1378 (m),
1347 (m), 1263 (s), 1180 (s), 1154 (s), 1081 (s), 1054 (w), 964 (m), 751 (s), 654
(w), 509 (w).
Experimental example
The azacyclo-transition metal Zn complex of the present invention inhibitory action to α-amylase, its suppression ratio assay method is:
1, the preparation of reagent
The preparation of DNS reagent weighs 1.625g 3,5 one dinitrosalicylic acids, adds 2mol/l sodium hydroxide solution 81.25ml,
Glycerol 11.25g, shakes up, and adds water and is settled to 250ml, and ultrasonic dissolution assisting, after all dissolving and clarifying, is cooled to room temperature,
Put in brown reagent bottle standby.
The preparation of α-amylase liquid weighs 0.06g α-amylase, by 0.2mol/l, pH6.5PBS buffer constant volume chamber 100ml,
Ultrasonic dissolution assisting, filters, to obtain final product, and this reagent is the most now with the current.
2, take 4 brace plug test tubes and be all sequentially added into α-amylase liquid 1ml, the 2mg/ml soluble starch solution 1ml of 600 μ g/ml,
And add following reagent according to setting:
Test tube 1:0.25mg/ml, 0.5mg/ml or 1mg/ml acarbose 1ml
The azacyclo-transition metal Zn complex 1ml of test tube 2:0.25mg/ml, 0.5mg/ml or 1mg/ml present invention
Test tube 3:0.25mg/ml, 0.5mg/ml or 1mg/ml Zn (Ac)2 1ml
Test tube 4:0.25mg/ml, 0.5mg/ml or 1mg/ml 1-(BTA-1-methyl)-1-(2-ethyl imidazol(e)) 1ml
After mixing, 37 DEG C of heating in water bath for reaction.Often manage accurate timing 20min, to add DNS reagent 5ml termination reaction.Boiling
(colour developing principle is: under α-amylase existence condition, add soluble starch and test sample, by measuring in water-bath 5min colour developing
The amount of the reducing sugar generated by α-amylase degraded evaluates the activity of test sample, and reducing sugar can be by 3,5 under alkaline environment
One dinitrosalicylic acid reduction, generates henna amino-compound, has absorption maximum at 540nm), after being cooled to room temperature,
Absorbance is measured at 540nm.
The computing formula of suppression ratio is:
In formula: Emin is to replace test liquid and α-amylase with water, Emax is to replace test liquid with water, and background radix is with water
Replace soluble starch solution.
The inhibitory activity of the α-amylase of coordination compound of the present invention see table:
The compound of the variable concentrations suppression ratio to α-amylase
Note: AEmin=0.134, AEmax=0.622
From the point of view of the measurement result that external hypoglycemic activity is tested, ligand 1-(BTA-1-methyl)-1-(2-ethyl imidazol(e))
α-amylase is had certain inhibitory action, the azacyclo-transition metal Zn complex of the present invention inhibitory action ratio to α-amylase
Relatively strong, it is better than conventional hypoglycemic medicine acarbose.And only Zn (Ac)2Test liquid bright to the inhibitory action of α-amylase
Aobvious more weak, it is not only below 1-(BTA-1-methyl)-1-(2-ethyl imidazol(e)) and azacyclo-transition metal Zn complex,
Acarbose to be less than.This shows, only with regard to external hypoglycemic activity from the point of view of, the present invention synthesis azacyclo-transition metal zinc coordinate
Thing has bigger superiority.Based on this, this coordination compound can be carried out the research of further pharmacology and physiologically active.
Claims (8)
1. the azacyclo-transition metal Zn complex containing multiple coordination sites, it is characterised in that described azacyclo-transition metal
Zn complex is 1-(BTA-1-methyl)-1-(2-ethyl imidazol(e)) Zn complex, and molecular formula is
[Zn(SCN)2(C12H13N5)2]；Wherein, C12H13N5For ligand 1-(BTA-1-methyl)-1-(2-ethyl imidazol(e)),
Molecular structural formula is:
Azacyclo-transition metal Zn complex containing multiple coordination sites the most according to claim 1, it is characterised in that described
The preparation method of ligand 1-(BTA-1-methyl)-1-(2-ethyl imidazol(e)), comprise the following steps:
(1) 11.9g BTA, 30ml water and 30ml formaldehyde being mixed, heated and stirred makes solid dissolve, at 80 DEG C of bars
Heating in water bath 1h under part, cooling, it is filtrated to get product as white needles, obtains white crystal by re-crystallizing in ethyl acetate, be hydroxyl
Methyl benzotriazazole；
(2) methylol BTA 7.4g is added in single port bottle, drip 25ml SOCl2, mix and blend after completion of dropwise addition
30min, 80 DEG C of backflow 3h；The SOCl of excess is boiled off with Rotary Evaporators2, obtain white crystal, be chloromethyl benzo three nitrogen
Azoles；
(3) take 2-ethyl imidazol(e) 40mmol, be dissolved in 20ml DMSO, add the NaOH 80mmol pulverized, be heated to
60 DEG C, add 40mmol chloromethyl BTA, 60 DEG C of heating in water bath 1h, be cooled to room temperature, pour in 100g frozen water,
, there is precipitation, sucking filtration in stirring, and precipitation washes with water 3 times, obtains crude product；
(4) crude product recrystallization in ethyl acetate, obtains lacteous crystal, is ligand 1-(BTA-1-methyl)-1-
(2-ethyl imidazol(e)).
3. the preparation side of the azacyclo-transition metal Zn complex containing multiple coordination sites as described in any one of claim 1-2
Method, it is characterised in that comprise the following steps:
(1) accurately weigh transition metal zinc salt 0.02-0.04mmol, be dissolved in 4-6ml solvent, obtain zinc solution；
(2) accurately weigh ligand 1-(BTA-1-methyl)-1-(2-ethyl imidazol(e)) 0.02-0.03mmol, be dissolved in
In 4-6ml solvent, obtain ligand solution；
(3) accurately weigh 0.02-0.03mmol KSCN, be dissolved in 1-2ml water, obtain KSCN solution；And by KSCN
Solution adds in zinc solution, obtains mixed solution；
(4) ligand solution is added in mixed solution, mix homogeneously, filter, filtrate solubilizer to 14-18ml, quiet under room temperature
Put, to separating out colourless rectangle crystal, to obtain final product.
The preparation method of the azacyclo-transition metal Zn complex containing multiple coordination sites the most according to claim 3, its feature
Being, described transition metal zinc salt is zinc sulfate, zinc acetate, zinc nitrate or zinc chloride.
The preparation method of the azacyclo-transition metal Zn complex containing multiple coordination sites the most according to claim 3, its feature
Being, the solvent of step (1), (2) and (4) is the one in water, methanol, ethanol, dimethyl sulfoxide, acetonitrile or two
The mixture planted.
The preparation method of the azacyclo-transition metal Zn complex containing multiple coordination sites the most according to claim 3, its feature
It is, comprises the following steps:
(1) Zn (Ac) is accurately weighed20.02mmol, is dissolved in 4ml methanol, obtains zinc solution；
(2) accurately weigh ligand 1-(BTA-1-methyl)-1-(2-ethyl imidazol(e)) 0.02mmol, be dissolved in 4ml
In methanol, obtain ligand solution；
(3) accurately weigh 0.02mmol KSCN, be dissolved in 1ml water, obtain KSCN solution；And by KSCN solution
Add in zinc solution, obtain mixed solution；
(4) ligand solution is added in mixed solution, mix homogeneously, to filter, filtrate adds methanol to 14ml, left at room temperature,
To separating out colourless rectangle crystal, to obtain final product.
7. the azacyclo-transition metal Zn complex containing multiple coordination sites as claimed in claim 1 is in suppression α-amylase side
The application in face.
8. the azacyclo-transition metal Zn complex containing multiple coordination sites as claimed in claim 1 is preparing hypoglycemic medicine side
The application in face.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610555494.9A CN105968127B (en) | 2016-07-14 | 2016-07-14 | A kind of azacyclo- transition metal Zn complex containing multiple coordination sites, preparation method and application |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610555494.9A CN105968127B (en) | 2016-07-14 | 2016-07-14 | A kind of azacyclo- transition metal Zn complex containing multiple coordination sites, preparation method and application |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN105968127A true CN105968127A (en) | 2016-09-28 |
| CN105968127B CN105968127B (en) | 2017-08-25 |
Family
ID=56951599
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610555494.9A Expired - Fee Related CN105968127B (en) | 2016-07-14 | 2016-07-14 | A kind of azacyclo- transition metal Zn complex containing multiple coordination sites, preparation method and application |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105968127B (en) |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108586499A (en) * | 2018-07-27 | 2018-09-28 | 河南中医药大学 | A kind of azacyclo- transition metal copper complex of imidazole ring-containing and its preparation method and application |
| CN108586542A (en) * | 2018-06-08 | 2018-09-28 | 河南中医药大学 | A kind of ONO types Schiff-base Palladium (II) complex and its preparation method and application containing multiple coordination sites |
| CN108659022A (en) * | 2018-07-27 | 2018-10-16 | 河南中医药大学 | 1- (benzotriazole -1- methyl) -1- (2-ethyl-4-methylimidazoles）Zn complex and preparation method thereof |
| CN108774252A (en) * | 2018-07-27 | 2018-11-09 | 河南中医药大学 | 1- (benzotriazole -1- methyl) -1- (2,4- methylimidazole) Zn complex and preparation method thereof |
| CN111892715B (en) * | 2020-08-13 | 2021-04-16 | 广东泰金智能包装有限公司 | Metal organic framework material and preparation method and application thereof |
| CN116218611A (en) * | 2021-12-06 | 2023-06-06 | 上海新阳半导体材料股份有限公司 | Polyimide cleaning fluid |
| CN116218610A (en) * | 2021-12-06 | 2023-06-06 | 上海新阳半导体材料股份有限公司 | Preparation method of polyimide cleaning liquid |
| CN116218612A (en) * | 2021-12-06 | 2023-06-06 | 上海新阳半导体材料股份有限公司 | Application of polyimide cleaning solution in cleaning semiconductor device |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102060864A (en) * | 2010-12-29 | 2011-05-18 | 河南中医学院 | Salicylide schiff's base and transition metal compound and preparation method thereof |
| CN102070657A (en) * | 2010-12-21 | 2011-05-25 | 河南中医学院 | Bis-o-vanillin ethylene diamine schiff base and transitional metal coordination compound and preparation method thereof |
-
2016
- 2016-07-14 CN CN201610555494.9A patent/CN105968127B/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102070657A (en) * | 2010-12-21 | 2011-05-25 | 河南中医学院 | Bis-o-vanillin ethylene diamine schiff base and transitional metal coordination compound and preparation method thereof |
| CN102060864A (en) * | 2010-12-29 | 2011-05-18 | 河南中医学院 | Salicylide schiff's base and transition metal compound and preparation method thereof |
Non-Patent Citations (3)
| Title |
|---|
| HUAI-XIA YANG等: "Bis{1-[(1H-benzimidazol-1-yl)methyl-kN3]-1H-1,2,3,4-tetrazole}silver(I)", 《ACTA CRYSTALLOGRAPHICA, SECTION E: STRUCTURE REPORTS》 * |
| SHUXUN YAN等: "Syntheses, Crystal Structures, and Fluorescent Properties of Three Complexes Constructed From 2-(1H-imidazole-1-ylmethyl)-1H-benzimidazole", 《SYNTHESIS AND REACTIVITY IN INORGANIC, METAL-ORGANIC, AND NANO-METAL CHEMISTRY》 * |
| XIANGRU MENG等: "Syntheses, structures and thermal stabilities of eight 1-((benzotriazol-yl)methyl)-1H-1,3-imidazole complexes based on different anions", 《JOURNAL OF MOLECULAR STRUCTURE》 * |
Cited By (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108586542A (en) * | 2018-06-08 | 2018-09-28 | 河南中医药大学 | A kind of ONO types Schiff-base Palladium (II) complex and its preparation method and application containing multiple coordination sites |
| CN108586542B (en) * | 2018-06-08 | 2020-06-02 | 河南中医药大学 | ONO type Schiff base palladium (II) complex containing multiple coordination sites as well as preparation method and application thereof |
| CN108586499A (en) * | 2018-07-27 | 2018-09-28 | 河南中医药大学 | A kind of azacyclo- transition metal copper complex of imidazole ring-containing and its preparation method and application |
| CN108659022A (en) * | 2018-07-27 | 2018-10-16 | 河南中医药大学 | 1- (benzotriazole -1- methyl) -1- (2-ethyl-4-methylimidazoles）Zn complex and preparation method thereof |
| CN108774252A (en) * | 2018-07-27 | 2018-11-09 | 河南中医药大学 | 1- (benzotriazole -1- methyl) -1- (2,4- methylimidazole) Zn complex and preparation method thereof |
| CN108659022B (en) * | 2018-07-27 | 2020-09-25 | 河南中医药大学 | 1- (benzotriazole-1-methyl) -1- (2-ethyl-4-methylimidazole) zinc complex and preparation method thereof |
| CN108774252B (en) * | 2018-07-27 | 2021-01-08 | 河南中医药大学 | 1- (benzotriazole-1-methyl) -1- (2, 4-dimethyl imidazole) zinc complex and preparation method thereof |
| CN111892715B (en) * | 2020-08-13 | 2021-04-16 | 广东泰金智能包装有限公司 | Metal organic framework material and preparation method and application thereof |
| CN116218611A (en) * | 2021-12-06 | 2023-06-06 | 上海新阳半导体材料股份有限公司 | Polyimide cleaning fluid |
| CN116218610A (en) * | 2021-12-06 | 2023-06-06 | 上海新阳半导体材料股份有限公司 | Preparation method of polyimide cleaning liquid |
| CN116218612A (en) * | 2021-12-06 | 2023-06-06 | 上海新阳半导体材料股份有限公司 | Application of polyimide cleaning solution in cleaning semiconductor device |
Also Published As
| Publication number | Publication date |
|---|---|
| CN105968127B (en) | 2017-08-25 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN105968127A (en) | Azacyclic transition metal zinc complex containing multiple coordination sites, and preparation method and application of azacyclic transition metal zinc complex | |
| CN106188103B (en) | A kind of azacyclo- transition metal copper complex containing multiple coordination sites, preparation method and application | |
| CN103193627B (en) | Crystal formation of a kind of prostaglandin analogue and its production and use | |
| CN102939089A (en) | Method of treating obesity using antioxidant inflammation modulators | |
| CN102178741B (en) | Guava leaf extract with function of reducing blood sugar as well as preparation method and application thereof | |
| CN103936725A (en) | C crystal form of canagliflozin and crystal preparation method of canagliflozin | |
| CN107531745B (en) | A kind of new 18 α-Enoxolone derivative and its medical usage | |
| CN102391336B (en) | Compound and preparation method and use thereof | |
| CN108014118B (en) | A kind of purposes of notoginsenoside Ft1 | |
| CN102603575B (en) | Rhein-arginine eutectic compound, and preparation method, purification method and application thereof in preparation of medicines for treating diabetic complications | |
| CN103599117B (en) | Use of szechuan melandium root pentacyclic triterpenoid saponin compound in preparation of drug for reducing blood sugar | |
| CN103550281B (en) | The pharmaceutical composition of a kind of prevention and therapy diabetes and complication thereof and preparation thereof | |
| CN108451959A (en) | The application of galloyl glucose glycoside derivative and the pharmaceutical composition for treating hyperuricemia | |
| CN101230035B (en) | Aspartic acid amlodipine series salt as well as preparation method, composition, preparation and tablets thereof | |
| CN102688248B (en) | Use of bufadienolide compound in preparing medicines for treating oral mucosal malignant tumors | |
| CN101066982B (en) | Amino acid-glucose derivative 99m TC compound and its prepn process | |
| CN108586542A (en) | A kind of ONO types Schiff-base Palladium (II) complex and its preparation method and application containing multiple coordination sites | |
| CN102060864A (en) | Salicylide schiff's base and transition metal compound and preparation method thereof | |
| CN101683320A (en) | Olprinone hydrochloric parenteral solution and method for preparing same | |
| CN103408554B (en) | Hypertensive activity reducing pyrrole coumarins compound and preparation method thereof | |
| CN102614247A (en) | Application of red bean (bean, winged bean) extracts in preparing anti-diabetes medicines | |
| CN104013614B (en) | A kind of golden larch lactone H preparation method and application | |
| CN106432136B (en) | A kind of Hydrochioro and atenolol are total to unformed system and preparation method thereof | |
| CN103585469B (en) | A kind of gymnadenia conopsea medicinal composition and its preparation method and application | |
| CN104447852A (en) | Novel schiff base vanadium oxide compound as well as preparation method and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20170825 Termination date: 20180714 |