CN104447852B - Schiff base vanadium oxide compound as well as preparation method and application thereof - Google Patents
Schiff base vanadium oxide compound as well as preparation method and application thereof Download PDFInfo
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- CN104447852B CN104447852B CN201410652404.9A CN201410652404A CN104447852B CN 104447852 B CN104447852 B CN 104447852B CN 201410652404 A CN201410652404 A CN 201410652404A CN 104447852 B CN104447852 B CN 104447852B
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- salicylide
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Abstract
The invention discloses a novel schiff base vanadium oxide compound as well as a preparation method and application thereof. The novel schiff base vanadium oxide compound is named N,N'-bis(salicylidene)-4,5-dichloro-1,2-phenylenediamine shrinked-diamine oxovanadium and has a molecular formula of [C20H12Cl2N2O3V] and molecular weight FW equal to 450.16, and a chemical structural formula of the novel schiff base vanadium oxide compound is as shown in the specification. The novel schiff base vanadium oxide compound disclosed by the invention has excellent hypoglycemic activity and can be used for preparing a drug for treating diabetes.
Description
Technical field
The present invention relates to technical field of medical chemistry, more particularly, to a kind of new schiff base anadium complex and its preparation side
Method and purposes.
Background technology
Diabetes are a kind of chronic metabolic disease being caused due to shortage insulin, and its main clinical characteristics is patient's blood
Glucose content in liquid is higher than normal population.The whole world there are about 35,000,000 diabetics at present according to statistics, and to the year two thousand thirty
This numeral may double.Diabetes can be divided into I type and II type by pathological characteristics.I type is due to internal insulin secretion
Deficiency causes, and generally adopts the treatment of external source supplementation with insulin；II type is that target cell causes to insulin generation resistance effect,
Mostly occur in obese people, still lack safely and effectively treatment meanss at present.Treatment type Ⅰ diabetes mellitus method is mainly every at present
It gives patient's insulin injection, and this is substantial amounts of inconvenient and painful to bringing on minimal invasive treatment and work.And treat in the market
The medicine of type Ⅱdiabetes mellitus mainly has sulphonyl to urinate, sulfanilamide, and the medicine such as metformin has no effectively to the side effect that diabetes cause
Treatment.Vanadium is trace element needed by human, and a large amount of further investigations and investigation show generally existing vanadium in diabeticss body
Lack and not enough state, the compound of oral vanadium can improve the state of an illness, reduce blood glucose, I type and type Ⅱdiabetes mellitus are all had
Effect.It is taken as that the compound of vanadium has elimination insulin resistance or " Insulin-Like " (Insulin-mimics) effect.And vanadium
Compound being capable of oral administration.Therefore for diabetes patient, reducing or eliminating that the dependence to injectivity insulin just becomes can
Energy.
Content of the invention
It is an object of the present invention to provide a kind of dilute Buddhist alkali vanadium complex of dichloro, there is anti-diabetic activity
Feature.
The present invention another object is that a kind of method preparing dichloro dilute Buddhist alkali vanadium complex of proposition.
The present invention adopts the following technical scheme that：
The title of the new schiff base anadium complex of the present invention is：N, N'- bis- (salicylidene) -4,5- two chloro- 1,
2- phenylenediamine contracting diamine closes vanadyl, and molecular formula is：[C20H12Cl2N2O3V], molecular weight FW=450.16, its chemical structural formula is such as
Under：
The synthetic route of the new schiff base anadium complex of the present invention is as follows：
Concrete preparation process is as follows：
(1) 4,5- dichloro o-phenylenediamine is taken to be dissolved in ethanol solution, mole body of 4,5- dichloro o-phenylenediamines and ethanol
Long-pending ratio is 1-5:30mmol/ml；Salicylide is taken to be dissolved in ethanol solution, the molal volume of salicylide and ethanol is than for 6-12:
15mmol/ml；Salicylide solution is dropwise instilled in ethanol solution by 50-70 DEG C of water bath with thermostatic control/oil bath, 4,5- dichloro neighbour's benzene
Diamidogen is 1-5 with the mol ratio of salicylide:6-12, mixing, reaction backflow 3-5h, there is yellow flocculent deposit to separate out, cooling, take out
Filter, carries out recrystallization in ethanol, is precipitated, and dries, obtains part；
(2) part obtaining step (1) is dissolved in acetonitrile and obtains ligand solution, the molal volume ratio of part and acetonitrile
For 0.5-2:13mmol/ml；By VOSO4·5H2O is dissolved in the water and obtains metal salt solution, VOSO4·5H2O and water mole
Volume ratio is 0.5-2:20mmol/ml；Metal salt solution is added dropwise in ligand solution, part and VOSO4·5H2O mole
Than for 0.5-2:0.5-2, stirs 20-40min, produces brown precipitate, filters, that is, the dilute Buddhist alkali vanadium oxidation obtaining the present invention is closed
Thing.
In step (1), preferably：The molal volume of 4,5- dichloro o-phenylenediamine and ethanol is than for 3:30mmol/ml；Salicylide
With the molal volume of ethanol than for 9:15mmol/ml；4,5- dichloro o-phenylenediamine is 3 with the mol ratio of salicylide:9.
In step (1), dropwise salicylide solution is instilled in ethanol solution preferably in 60 DEG C of water bath with thermostatic control/oil baths, mix
Close, reaction backflow 4h.
In step (2), preferably：The molal volume of part and acetonitrile is than for 1:13mmol/ml；VOSO4·5H2O is rubbed with water
Your volume ratio is 1:20mmol/ml；Part and VOSO4·5H2The mol ratio of O is 1:1.
In step (2), preferably stir 30min.
The new schiff base anadium complex of the present invention has excellent hypoglycemic activity, can be used for preparation and treats anti-glycosuria
Medicine.
Specific embodiment
Below by specific embodiment, the present invention will be further elaborated.
Embodiment 1：
(1) 4,5- dichloro o-phenylenediamine is taken to be dissolved in ethanol solution, mole body of 4,5- dichloro o-phenylenediamines and ethanol
Long-pending ratio is 1:30mmol/ml；Salicylide is taken to be dissolved in ethanol solution, the molal volume of salicylide and ethanol is than for 12:
15mmol/ml；Salicylide solution is dropwise instilled in ethanol solution by 50 DEG C of water bath with thermostatic control/oil baths, 4,5- dichloro neighbour's benzene two
Amine is 1 with the mol ratio of salicylide:12, mixing, reaction backflow 5h, there is yellow flocculent deposit to separate out, cooling, sucking filtration, in ethanol
In carry out recrystallization, be precipitated, dry, obtain part；
(2) part obtaining step (1) is dissolved in acetonitrile and obtains ligand solution, the molal volume ratio of part and acetonitrile
For 0.5:13mmol/ml；By VOSO4·5H2O is dissolved in the water and obtains metal salt solution, VOSO4·5H2O and mole body of water
Long-pending ratio is 2:20mmol/ml；Metal salt solution is added dropwise in ligand solution, part and VOSO4·5H2The mol ratio of O is
0.5:2, stir 20min, produce brown precipitate, filter, that is, obtain the schiff base anadium complex of the present invention, will be precipitated and dissolved in
In DMSO, retain filtrate, after 30d, DMSO solution separates out yellow bulk complex crystal, suitable X-ray single crystal diffraction simultaneously.Produce
Rate is 75%.
Embodiment 2：
(1) 4,5- dichloro o-phenylenediamine is taken to be dissolved in ethanol solution, mole body of 4,5- dichloro o-phenylenediamines and ethanol
Long-pending ratio is 5:30mmol/ml；Salicylide is taken to be dissolved in ethanol solution, the molal volume of salicylide and ethanol is than for 6:
15mmol/ml；Salicylide solution is dropwise instilled in ethanol solution by 70 DEG C of water bath with thermostatic control/oil baths, 4,5- dichloro neighbour's benzene two
Amine is 5 with the mol ratio of salicylide:6, mixing, reaction backflow 3h, there is yellow flocculent deposit to separate out, cooling, sucking filtration, in ethanol
Carry out recrystallization, be precipitated, dry, obtain part；
(2) part obtaining step (1) is dissolved in acetonitrile and obtains ligand solution, the molal volume ratio of part and acetonitrile
For 2:13mmol/ml；By VOSO4·5H2O is dissolved in the water and obtains metal salt solution, VOSO4·5H2O and the molal volume of water
Than for 0.5:20mmol/ml；Metal salt solution is added dropwise in ligand solution, part and VOSO4·5H2The mol ratio of O is 2:
0.5, stir 40min, produce brown precipitate, filter, that is, obtain the schiff base anadium complex of the present invention, will be precipitated and dissolved in
In DMSO, retain filtrate, after 30d, DMSO solution separates out yellow bulk complex crystal, suitable X-ray single crystal diffraction simultaneously.Produce
Rate is 78%.
Embodiment 3：
(1) take 4,5- dichloro o-phenylenediamine (3mmol, 0.51g) to be dissolved in 30mL ethanol solution, take salicylide
(9mmol, 1.05g) is dissolved in 15mL ethanol solution, dropwise instills salicylide solution in 60 DEG C of water bath with thermostatic control/oil baths,
Both mixing.Reaction backflow 4h, has yellow flocculent deposit to separate out, cooling, sucking filtration.Carry out recrystallization in ethanol, sunk
Form sediment, dry, obtain part.
(2) the above-mentioned part (1mmol, 0.383g) that obtains is dissolved in 13mL MeCN, VOSO4·5H2O (1mmol, 0.254g)
It is dissolved in 20mL water.Under stirring, metal salt solution is added dropwise in ligand solution, stirs 30min, produce brown precipitate,
Filter, will be precipitated and dissolved in DMSO, retain filtrate simultaneously, after 30d, DMSO solution separates out yellow bulk complex crystal, is suitable for
X-ray single crystal diffraction.Yield is 80%.
The chemical characteristic parameter of above-mentioned prepared schiff base anadium complex is：
Elementary analysiss Anal.Calcd.for C20H12Cl2N2O3V:C, C, 53.31；H, 2.67；N, 6.22, experiment value is：
C, 53.19；H, 2.68；N, 6.28；Infrared spectrum IR (KBr disk):ν(cm-1)=1601,1496 (νC=N),730,(νc-cl)；
Its molecular formula C20H12Cl2N2O3V, its molecular weight FW=450.16.
Dilute Buddhist alkali manganese compound prepared by the embodiment of the present invention 3 is used in the experiment treat diabetes it was demonstrated that having bright
Aobvious hypoglycemic activity.Specifically experimentation is：Healthy ICR mice (♂), adaptability is fed 3 days, chooses body weight ＞ 24g's
Mice carries out modeling.Modeling method：Tail vein injection alloxan after mice fasting 6h, dosage 65mg/kg, administered volume
10ml/kg.After injection alloxan, docking in the 4th day takes blood, measures blood glucose with Glucose estimation kit, choose blood glucose value >=
The mice of 11.1mmol/L is diabetic mice, by blood glucose value and body weight random packet, every group 10.Normal group then injects
Equal-volume normal saline (NS).Test mice is randomly divided into normal group, diabetic groups, diabetes+manganese compound group by blood glucose.Point
Group situation is as follows：
1. diabetic model group：0.5%CMC-Na (containing 0.9%NaCl)；
2. positive group：Metformin Hydrochloride Tablets dosage 250mg/kg, a piece of is dissolved in 10ml0.5%CMC-Na；
③[C20H12Cl2N2O3V] group：Dosage 77mg/kg, weighs 0.077g and is dissolved in 10ml0.5%CMC-Na.
All samples are 3 days configuration amount, 4 DEG C of preservations.Daily gastric infusion once, weekly 1 hour after gastric infusion
Measure blood glucose, fasting 2.5 hours before blood sugar detection.
Experimental result carries out statistical disposition, and result is as shown in table 1：
Table 1 coordination compound [C20H12Cl2N2O3V] administration impact to alloxan diabeteses mouse blood sugar in 3 weeks ( n
≧9)
Note：Compared with model group, * P ＜ 0.05, * * P ＜ 0.01
From table 1, it is administered first week coordination compound [C20H12Cl2N2O3V] administration group mice fasting blood glucose level obvious
Less than model group (P ＜ 0.05), effect lasts 3 weeks.
Two weeks carry out oral glucose tolerance (OGTT) experiment, the results are shown in Table 2, gavage gives glucose (2g/kg),
The blood glucose till of diabetic mice raises, and arrives peak after 60min.Metformin administration group blood sugar level ascensional range
Less than model group, during 120min, metformin administration group blood sugar level is significantly lower than model group (P ＜ 0.05).
Coordination compound [C20H12Cl2N2O3V] it is administered 120min in alloxan diabeteses mice, blood sugar level substantially reduces
(with model group ratio, P ＜ 0.05).This shows, coordination compound [C20H12Cl2N2O3V] removing of blood sugar level can be accelerated, four can be improved
The carbohydrate tolerance of oxygen pyrimidine diabetic mice.
Table 2 coordination compound [C20H12Cl2N2O3V] administration impact to alloxan diabeteses mice OGTT in 2 weeks (
n≧9)
Note：Compared with model group, * P ＜ 0.05, * * P ＜ 0.01
Although an embodiment of the present invention has been shown and described, for the ordinary skill in the art, permissible
Understand and can carry out multiple changes, modification, replacement to these embodiments without departing from the principles and spirit of the present invention
And modification, the scope of the present invention be defined by the appended.
Claims (7)
1. a kind of schiff base anadium complex it is characterised in that：The title of described schiff base anadium complex is：N, N'- bis-
Chloro- 1, the 2- phenylenediamine contracting diamine of (salicylidene) -4,5- bis- closes vanadyl, and molecular formula is：[C20H12Cl2N2O3V], its chemistry knot
Structure formula is as follows：
2. a kind of method preparing schiff base anadium complex as claimed in claim 1 it is characterised in that：Described preparation method
Synthetic route as follows：
The comprising the following steps that of described preparation method：
(1) 4,5- dichloro o-phenylenediamine is taken to be dissolved in ethanol solution, the molal volume ratio of 4,5- dichloro o-phenylenediamines and ethanol
For 1-5:30mmol/ml；Salicylide is taken to be dissolved in ethanol solution, the molal volume of salicylide and ethanol is than for 6-12:
15mmol/ml；Salicylide solution is dropwise instilled in ethanol solution by 50-70 DEG C of water bath with thermostatic control/oil bath, 4,5- dichloro neighbour's benzene
Diamidogen is 1-5 with the mol ratio of salicylide:6-12, mixing, reaction backflow 3-5h, there is yellow flocculent deposit to separate out, cooling, take out
Filter, carries out recrystallization in ethanol, is precipitated, and dries, obtains part；
(2) part obtaining step (1) is dissolved in acetonitrile and obtains ligand solution, and part with the molal volume ratio of acetonitrile is
0.5-2:13mmol/ml；By VOSO4·5H2O is dissolved in the water and obtains metal salt solution, VOSO4·5H2O and mole body of water
Long-pending ratio is 0.5-2:20mmol/ml；Metal salt solution is added dropwise in ligand solution, part and VOSO4·5H2The mol ratio of O
For 0.5-2:0.5-2, stirs 20-40min, produces brown precipitate, filters, that is, obtains schiff base anadium complex.
3. preparation method as claimed in claim 2 it is characterised in that：In step (1), 4,5- dichloro o-phenylenediamines and ethanol
Molal volume is than for 3:30mmol/ml；The molal volume of salicylide and ethanol is than for 9:15mmol/ml；4,5- dichloro neighbour's benzene two
Amine is 3 with the mol ratio of salicylide:9.
4. preparation method as claimed in claim 2 it is characterised in that：In step (1), in 60 DEG C of water bath with thermostatic control/oil baths by
Drip and salicylide solution is instilled in ethanol solution, 4,5- dichloro o-phenylenediamines are 1-5 with the mol ratio of salicylide:6-12, mixing,
Reaction backflow 4h.
5. preparation method as claimed in claim 2 it is characterised in that：In step (2), part with the molal volume ratio of acetonitrile is
1:13mmol/ml；VOSO4·5H2The molal volume of O and water is than for 1:20mmol/ml；Part and VOSO4·5H2The mol ratio of O
For 1:1.
6. preparation method as claimed in claim 2 it is characterised in that：In step (2), stir 30min.
7. schiff base anadium complex as claimed in claim 1 is for the purposes in preparation treatment diabetes medicament.
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| CN101857642A (en) * | 2009-04-10 | 2010-10-13 | 烟台海岸带可持续发展研究所 | Polysaccharide derivative and vanadium complex application thereof |
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| CN103232486A (en) * | 2013-05-07 | 2013-08-07 | 山西大学 | Vanadium oxide complex as well as preparation method and application thereof |
| CN103316017A (en) * | 2013-01-09 | 2013-09-25 | 昆明医科大学 | Bis(alpha-furancarboxylato)oxovanadium composition for treatment of diabetes |
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Patent Citations (8)
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| CN1355169A (en) * | 2000-11-28 | 2002-06-26 | 昆明贵金属研究所 | Vanadium compound and its preparing process and usage |
| CN1687083A (en) * | 2005-03-28 | 2005-10-26 | 南开大学 | Compound containing vanadium for treating diabetes and preparation method thereof |
| CN101205236A (en) * | 2006-12-18 | 2008-06-25 | 金文正 | Pyridinedicarboxylic acid vanadyl complexes as well as agent, tablet, capsule and uses thereof |
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| CN103316017A (en) * | 2013-01-09 | 2013-09-25 | 昆明医科大学 | Bis(alpha-furancarboxylato)oxovanadium composition for treatment of diabetes |
| CN103232486A (en) * | 2013-05-07 | 2013-08-07 | 山西大学 | Vanadium oxide complex as well as preparation method and application thereof |
| CN103923117A (en) * | 2014-04-03 | 2014-07-16 | 华东师范大学 | Preparation method of Schiff base vanadium oxide coordination compound crystal with biological activity |
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