CN109336800A - A kind of DHNB contracting phenyl thiosemicarbazide compound and its preparation method and application - Google Patents
A kind of DHNB contracting phenyl thiosemicarbazide compound and its preparation method and application Download PDFInfo
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- CN109336800A CN109336800A CN201811081638.7A CN201811081638A CN109336800A CN 109336800 A CN109336800 A CN 109336800A CN 201811081638 A CN201811081638 A CN 201811081638A CN 109336800 A CN109336800 A CN 109336800A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C337/00—Derivatives of thiocarbonic acids containing functional groups covered by groups C07C333/00 or C07C335/00 in which at least one nitrogen atom of these functional groups is further bound to another nitrogen atom not being part of a nitro or nitroso group
- C07C337/06—Compounds containing any of the groups, e.g. thiosemicarbazides
- C07C337/08—Compounds containing any of the groups, e.g. thiosemicarbazides the other nitrogen atom being further doubly-bound to a carbon atom, e.g. thiosemicarbazones
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/06—Antigout agents, e.g. antihyperuricemic or uricosuric agents
Abstract
The invention discloses a kind of chemical synthetic drug DHNB contracting phenyl thiosemicarbazide, structure is as follows:The preparation method of above-mentioned chemical synthetic drug DHNB contracting phenyl thiosemicarbazide, 3 shown in structural formula (I), 4- dihydroxy -5- nitrobenzaldehyde (DHNB) is raw material, condensation reaction, DHNB contracting phenyl thiosemicarbazide shown in composite structure formula (III) are carried out through aldehyde amine with 4- phenyl thiosemicarbazide shown in structural formula (II) in solvent methanol；The present invention reduces internal uric acid synthesis, to effectively treat gout and hyperuricemia by inhibiting xanthine oxidase (XOD).
Description
Technical field
The present invention relates to new drug development and application field, specifically a kind of chemical synthetic drug DHNB contracting phenyl thiosemicarbazide
And preparation method thereof and prevent, treat the purposes of gout and hyperuricemia.
Background technique
Gout is crystal correlation arthropathy caused by a kind of monosodium urate salt (MSU) deposition, with purine metabolic disturbance or
Hyperuricemia caused by underexcretion (hyperuricemia, HUA) is directly related.The illness rate of China HUA be in by
Year ascendant trend, age of onset more become to becoming younger, and have become the second largest metabolic disease for being only second to diabetes, to society with
Family brings huge economy and mental burden.The epidemiological study of last decade shows, China different regions HUA illness rate
There are biggish difference, are 5.46%~19.30%, and wherein male is 9.2%~26.2%, and women is 0.7%~10.5%,
Overall male is higher than women.Gout be long-term disorders of purine metabolism (or) underexcretion, blood uric acid, which increases, causes tissue to damage
One group of clinical syndrome of wound, hyperuricemia is the most important biochemical basis of gout.Uric acid is decomposed by diet intake and in vivo
Purine compound generated in liver, by kidney excretion, remaining is drained about 2/3 uric acid by alimentary canal.Gout includes acute
Urarthritis and chronic gout stone disease, blood uric acid increase in addition to it can cause gout, also with kidney, endocrine metabolism and
The occurrence and development of the systemic diseases such as cardiovascular and cerebrovascular are related.
The conventional medicine for the treatment of gout mainly has colchicin, non-steroid anti-inflammatory drug, allopurinol, Febuxostat at present
With Benzbromarone etc..These drugs with inhibit uric acid formation or (and) promote uric acid excretion reach alleviation and treatment gout with
The purpose of hyperuricemia.The synthesis of internal uric acid is related with purine metabolism, xanthine oxidase (XOD), is that internal uric acid is raw
At key enzyme, it can be catalyzed hypoxanthine and xanthine is converted into uric acid.Body hyperuricuria can lead hyperuricemia, in turn
It can lead to gout.Allopurinol and Febuxostat are the inhibitor of XOD, both drugs reduce internal uric acid by inhibiting XOD
Synthesis, to effectively treat gout.But they all have certain side effect in clinical use, as allopurinol can cause skin
The hypersensitivity syndrome such as lethal exfoliative dermatitis can occur for skin allergic reaction and hepatic and renal function damage, serious person；Fei Busuo
It is smooth to cause hepatic disorder, nausea, fash etc..The adverse reaction for taking Benzbromarone has upset,gastro-intestinal, diarrhea, fash and liver
Functional lesion etc.；Colchicin adverse reaction is common nausea,vomiting,diarrhea, abdominal pain, hepatosis and renal impairment
Deng.It can be seen that the drug of current prevention and treatment gout and hyperuricemia is although more, but most of drug side-effect compared with
Greatly, quality of life is influenced.Therefore, the drug for developing novel treatment hyperuricemia and gout is still current the world of medicine's research
Hot spot.
Some researches show that it is one that 3,4- dihydroxy -5- nitrobenzaldehydes (DHNB), which belong to a kind of derivative of protocatechualdehyde,
Kind stronger XOD inhibitor can be used as and a kind of treat hyperuricemia and the potential drug of gout.DHNB can reduce high urine
Sour mice serum uric acid level, and the DHNB of large dosage does not have any side effect (500mg/kg) to mouse.But DHNB inhibits XOD
Activity has the defect of time dependence, and action time is extremely short, and it inhibits XOD ability weaker than Allopurinol.
Summary of the invention
Present invention aims to overcome that the prior art is insufficient, realistic development is adapted to, a kind of chemical synthetic drug DHNB is provided
Contracting phenyl thiosemicarbazide and preparation method thereof and the purposes for preventing, treating gout and hyperuricemia, to solve above-mentioned background
The problem of being proposed in technology.
In order to achieve the above objectives, The technical solution adopted by the invention is as follows:
A kind of chemical synthetic drug DHNB contracting phenyl thiosemicarbazide, structure are as follows:
The preparation method of above-mentioned chemical synthetic drug DHNB contracting phenyl thiosemicarbazide, with 3,4- bis- shown in structural formula (I)
Hydroxyl -5- nitrobenzaldehyde (DHNB) is raw material, is passed through in solvent methanol with 4- phenyl thiosemicarbazide shown in structural formula (II)
Aldehyde amine carries out condensation reaction, DHNB contracting phenyl thiosemicarbazide shown in composite structure formula (III), wherein shown in structural formula (I)
The molar ratio of 4- phenyl thiosemicarbazide shown in 3,4- dihydroxy -5- nitrobenzaldehydes (DHNB) and structural formula (II) is 1.0~
1.05:1；The reaction equation of the above process is as follows.
Above-mentioned chemical synthetic drug DHNB contracting phenyl thiosemicarbazide prevents, treats gout and the purposes of hyperuricemia exists
In, the DHNB contracting phenyl thiosemicarbazide as active pharmaceutical ingredient be configured to tablet, capsule, granula, injection, liposome or
Sustained-release and controlled release preparation.
The DHNB contracting phenyl thiosemicarbazide can also be united and applied in pre- with allopurinol, Febuxostat or colchicin
Anti-, treatment gout and hyperuricemia.
The DHNB contracting phenyl thiosemicarbazide can also form corresponding metal complex with metal ion-chelant and be applied to
Prevent, treat gout and hyperuricemia.
Above-mentioned chemical synthetic drug DHNB contracting phenyl thiosemicarbazide prevents, treats the purposes of gout and hyperuricemia, makees
It is additive application in health food or feed.
Compared with prior art, the advantages and positive effects of the present invention are as follows:
The present invention provides a kind of chemical synthetic drug DHNB contracting phenyl thiosemicarbazides, and it is real that inside and outside pharmacodynamics is carried out to it
It tests, experiment in vivo includes measuring its influence to high lithemia model mice serum XOD, liver XOD and serum uric acid；It is external real
The inhibiting effect for measuring it to XOD using multi-function microplate reader is tested, its suppression mechanism is inquired into；And acute toxicity test is carried out, from
And obtain the xanthine oxidase inhibitor DHNB contracting phenyl thiosemicarbazide of high-efficiency low-toxicity.
DHNB contracting phenyl thiosemicarbazide Compound ira vitro inhibits XOD enzyme activity research to show: in xanthine oxidase system
In, the concentration of fixed xanthine changes the concentration of xanthine oxidase, the DHNB contracting phenyl thiosemicarbazide of various concentration is added,
Inhibiting effect of the DHNB contracting phenyl thiosemicarbazide to XOD of various concentration is measured respectively；With DHNB contracting phenyl thiosemicarbazide
The increase of concentration, DHNB contracting phenyl thiosemicarbazide compound enhance the inhibiting effect of XOD enzymatic activity, i.e., inhibiting rate is in concentration
Positive correlation；And DHNB contracting phenyl thiosemicarbazide is more significant compared with DHNB and positive control Allopurinol.
Influence in DHNB contracting phenyl thiosemicarbazide compound body to high lithemia model mice research shows that: DHNB contracting benzene
Base thiosemicarbazides can significantly reduce high lithemia model mice serum XOD vigor and serum uric acid level, and can significantly reduce high urine
Acid profile mouse liver XOD vigor；Inhibit XOD vigor and drop serum uric acid ability stronger than positive control Allopurinol.
Detailed description of the invention
Fig. 1 is the chemosynthesis reaction formula of DHNB contracting phenyl thiosemicarbazide of the present invention；
Fig. 2 is suppression result of the DHNB contracting phenyl thiosemicarbazide to the XOD of various concentration；
Fig. 3 is the Lineweaver-Burk curve that DHNB contracting phenyl thiosemicarbazide inhibits XOD catalysis；
Fig. 4~5 are inhibiting effect result of the DHNB contracting phenyl thiosemicarbazide to high lithemia model mice serum XOD vigor；
Fig. 6~7 are exercising result of the DHNB contracting phenyl thiosemicarbazide to high lithemia model mice blood uric acid；
Fig. 8 is inhibiting effect result of the DHNB contracting phenyl thiosemicarbazide to high lithemia model mice liver XOD vigor.
Specific embodiment
Specific embodiments of the present invention will now be described in detail with reference to the accompanying drawings.
The preparation of 1.DHNB contracting phenyl thiosemicarbazide compound, isolation and purification
A kind of chemical synthetic drug DHNB contracting phenyl thiosemicarbazide, structure are as follows:
The preparation method of above-mentioned chemical synthetic drug DHNB contracting phenyl thiosemicarbazide, includes the following steps:
Take 0.005mol 4- phenyl thiosemicarbazide in 500mL three-necked flask, the methanol for adding 80ml is heated to reflux, directly
It is completely dissolved to 4- phenyl thiosemicarbazide；The DHNB of 0.005mol is taken to be dissolved in the hot methanol of 100mL；To 4- phenyl amino sulphur
After urea is completely dissolved, the methanol solution dissolved with DHNB is slowly instilled in three-necked flask with constant pressure funnel, and in 20min
It inside drips off, instills 3 after dripping off into three-necked flask and drip glacial acetic acids and make catalyst, continue to be heated to reflux 2h, TLC tracking and monitoring,
Until raw material point disappears, then fully reacting；
Specific reaction equation is as follows:
The separation and purifying of above-mentioned chemical synthetic drug DHNB contracting phenyl thiosemicarbazide: DHNB contracting phenyl thiosemicarbazide methanol
Reaction solution (rufous liquid), vacuum distillation concentration, cooling that crystallization is precipitated, filtering, ice acetone washing, drying obtain brick-red wadding
Shape crystallization.
In-vitro Inhibitory Effect of the 2.DHNB contracting phenyl thiosemicarbazide to xanthine oxidase
2.1 experimental material DHNB contracting phenyl thiosemicarbazides, phosphate buffer (PBS), xanthine, xanthine oxidase
(XOD) and allopurinol etc..
2.2 experimental method
2.2.1 enzyme activity detection and sample inhibit XOD measurement
25 DEG C of reaction temperature, (PBS of the 0.05M pH=7.5 including the EDTA containing 1mM is buffered overall reaction system 0.3mL
Solution, 0.15mM xanthine substrate solution, 0.5IUmL-1XOD enzyme solutions), it is returned to zero with buffer, with software containing enzyme kinetics
Multi-function microplate reader measurement.Experimental setup normal group of (sample is not added), sample sets, by xanthine substrate solution 100uL, sample
Solution sequentially adds 96 orifice plates, other to be replaced with PBS, and the volume (300uL) for keeping whole system unanimously, it is molten to be eventually adding XOD
Liquid 3uL starting reaction measures the absorbance value at 290nm, and interval 10s record is primary, surveys 2min internal absorbance changing value altogether, with
Time is independent variable, and absorbance value is dependent variable, and available absorbance-time straight line calculates the slope of straight line
Rate(dA/min).Each sample needs operation repetitive 3 times, is averaged the inhibiting rate for calculating sample.Inhibiting rate (%)=
[(K1-K2)/K1] × 100%.Wherein K1 indicates that the straight slope normally organized, K2 indicate the straight slope of sample sets.With sample
Concentration is independent variable X, and inhibiting rate is dependent variable Y, calculates regression equation using SPSS19.0 statistical package.According to recurrence side
Journey calculates sample concentration when inhibiting rate is 50%, i.e. half-inhibitory concentration IC50。
2.2.2 DHNB contracting phenyl thiosemicarbazide is to XOD inhibiting mechanism
Referring to 2.2.1, in live body system, the DHNB contracting phenylamino of various concentration is added in immobilized substrate xanthine concentration
Base thiocarbamide changes the mass concentration of XOD, measures influence of the inhibitor of various concentration to XOD catalysis oxidation xanthine ability.With
The speed of enzymatic reaction maps to enzyme concentration, if a series of straight lines by origin are obtained, for reversible inhibition；If obtaining one group
Parallel lines, then for can not retroactive inhibition.
2.2.3 DHNB contracting phenyl thiosemicarbazide inhibits type to XOD
The mass concentration of fixed XOD, changes the concentration of substrates xanthine, measures the inhibitor of various concentration to enzyme activity
It influences.Pass through Lineweaver-Burk equation: 1/V=Km/Vmax*1/ [S]+1/Vmax mapping is it can be concluded that inhibit type.
2.3 experimental result
2.3.1 inhibiting effect of the DHNB contracting phenyl thiosemicarbazide to xanthine oxidase
The inhibiting rate and IC of DHNB, DHNB contracting phenyl thiosemicarbazide and positive reference substance Allopurinol to XOD50As shown in table 1.
The different samples of table 1 to the inhibiting effect result of xanthine oxidase (n=3,)
Table 1 shows that different samples are different to the inhibiting rate of XOD, and inhibiting rate and being positively correlated property of concentration, DHNB is to XOD's
IC50For 32.12 μm of ol/L, DHNB contracting phenyl thiosemicarbazide IC50For 0.05 μm of ol/L, inhibitory effect is more significant compared with DHNB, and
And inhibit XOD vigor than Allopurinol (IC50=6.75 μm of ol/L) it is stronger.
2.3.2 DHNB contracting phenyl thiosemicarbazide is to XOD inhibiting mechanism
Suppression result such as Fig. 2 institute of the DHNB contracting phenyl thiosemicarbazide to the xanthine oxidase catalysis xanthine of various concentration
Show, to yellow fast when DHNB contracting phenyl thiosemicarbazide concentration is respectively 0 μ g/mL, 0.01 μ g/mL, 0.02 μ g/mL and 0.03 μ g/mL
Four straight lines of the suppression result of the oxidase catalyzed xanthine of purine intersect at a point there is no parallel, show DHNB contracting benzene
Base thiosemicarbazides is the reversible inhibitor of xanthine oxidase.
2.3.3 DHNB contracting phenyl thiosemicarbazide inhibits type to XOD
In xanthine oxidase system, under identical XOD concentration conditions, change substrates xanthine in 300 μ of total system
Volume [50 μ L (3.8 μ g/mL), 60 μ L (4.564 μ g/mL), 70 μ L (5.32 μ g/mL), 80 μ L (μ g/mL), 100 μ L in L
(7.6 μ g/mL)], that is, mass concentration of the substrates xanthine in system is changed, is measured by microplate reader different dense at 290nm
The inhibitor DHNB contracting phenyl thiosemicarbazide of (0 μ g/mL, 0.01 μ g/mL, 0.02 μ g/mL, 0.03 μ g/mL) is spent to xanthine oxidase
Change the inhibiting effect of enzyme.Lineweaver-Burk curve is drawn with reciprocal map to corresponding concentration of substrate of straight slope.Knot
Fruit is as shown in figure 3, DHNB contracting phenyl thiosemicarbazide inhibits the Lineweaver-Burk curve of xanthine oxidase catalysis first
Quadrant has common intersection point, and intersection point is not fallen in reference axis, shows DHNB contracting phenyl thiosemicarbazide to xanthine oxidase
Suppression mechanism neither it is competitive nor uncompetitive therefore can tentatively judge DHNB contracting phenyl thiosemicarbazide to Huang
Purine oxidase suppression mechanism may be mixed type.
Influence of the 3.DHNB contracting phenyl thiosemicarbazide to high lithemia model mice
3.1 experimental animals choose healthy male mice in kunming 60, and weight 18-22g is tested by Jiangxi University of Traditional Chinese Medicine
Animal Science & Technology Center provides [experimental animal production licence number: SCXK (Jiangxi) 2018-003].Raising one week before experiment, to adapt to
Environment.Rearing conditions: 25 ± 2 DEG C of room temperature, relative humidity 60%-70%.
It is mixed that 3.2 medical fluids preparation each group gastric infusion drug and animal model substance are made into drug containing with 0.9%CMC-Na liquid
Suspension.
3.3 experimental method
3.3.1 animal model
With Oteracil Potassium and uric acid ip mouse, increases serum uric acid level, cause Studies on Animal Models of Hyperuricemic Mice.Male elder brother
It is low that bright kind of mouse adaptive feeding is randomly divided into physiological saline group, high lithemia model group, DHNB contracting phenyl thiosemicarbazide after a week
Dosage group, DHNB contracting phenyl thiosemicarbazide middle dose group, DHNB contracting phenyl thiosemicarbazide high dose group, totally 6 groups of allopurinol group,
Every group 10.In addition to physiological saline group, for other each groups with Oteracil Potassium and uric acid ip mouse, continuous 2d carries out modeling to increase
Serum uric acid level causes Studies on Animal Models of Hyperuricemic Mice.
3.3.2 experimental implementation
Physiological saline group and high lithemia model group press 20mLkg daily-1Dosage stomach-filling (ig) is raw containing 0.9%CMC-Na
Manage salt water, continuous 6d, allopurinol group (10mgkg-1) daily ig be administered once, continue 6d, DHNB contracting phenyl thiosemicarbazide is low
Dosage group is with 5mgkg-1Dosage, DHNB contracting phenyl thiosemicarbazide middle dose group are with 10mgkg-1Dosage, DHNB contracting phenylamino
Base thiocarbamide high dose group is with 20mgkg-1The daily ig of dosage is administered once, and continues 6d, since administration the 5th day, removes physiological saline
Group is outer, and 1h is intended to ip Oteracil Potassium and uric acid before the daily ig of other each groups is administered, and the dosage of Oteracil Potassium and uric acid is respectively
0.3g·kg-1And 0.25gkg-1, 1 time a day, continuous 2d carries out modeling.After 1h is administered in the 6th day ig from mouse femoral artery into
Row blood sampling, blood sample are respectively placed in 1.5mL centrifuge tube, 2h are solidified in 4 DEG C of refrigerators, in 3000rmin-1Low-temperature centrifugation 5min.
Every part of blood sample serum carries out serum uric acid level and serum XOD vitality test.After taking blood, dissection mouse takes liver tinfoil paper paper bag
After wrapping up in, XOD vigor to be measured in -20 DEG C of refrigerators is placed in through liquid nitrogen flash freezer.
3.1.3 biochemical indicator detects
XOD activity in measurement mouse serum uric acid level, blood and liver respectively.Each group mouse blood urine is detected using phosphotungstic acid method
Acid, enzymic colorimetric detect XOD activity.Concrete operations are carried out by kit specification.
3.2 experimental result
3.2.1 inhibiting effect of the DHNB contracting phenyl thiosemicarbazide to high lithemia model mice serum XOD vigor
Using phosphotungstic acid method detection physiological saline group, high lithemia model group, DHNB contracting phenyl thiosemicarbazide low dose group,
DHNB contracting phenyl thiosemicarbazide middle dose group, DHNB contracting phenyl thiosemicarbazide high dose group and allopurinol group mice serum XOD
Vigor, as shown in figure 4, the vigor of model group XOD and saline control group show extremely significant difference, show to test modeling at
Function.After modeling, DHNB contracting phenyl thiosemicarbazide middle dosage, DHNB contracting phenyl thiosemicarbazide high dose and positive drug allopurinol are equal
It can inhibit mice serum XOD vigor；Significant difference is presented in allopurinol group compared with model group；DHNB contracting phenyl amino sulphur
Extremely significant sex differernce is presented in urea middle dosage, high dose compared with model group.The above result shows that DHNB contracting phenyl thiosemicarbazide
There is good inhibiting effect to mice serum XOD vigor.
In addition, as shown in figure 5, DHNB contracting phenyl thiosemicarbazide middle dosage, high dose compared with positive drug allopurinol,
Significant difference is presented, shows have the function of more preferably inhibiting XOD vigor compared with allopurinol in DHNB contracting phenyl thiosemicarbazide.No
It is different to the inhibiting effect of mice serum XOD vigor with the DHNB contracting phenyl thiosemicarbazide of dosage, DHNB contracting phenyl thiosemicarbazide
Low dosage is bad to the inhibitory effect of XOD vigor；And DHNB contracting phenyl thiosemicarbazide middle dosage, high dose are to mice serum XOD
The inhibiting effect of vigor has extremely significant sex differernce compared with allopurinol；Meanwhile DHNB contracting phenyl thiosemicarbazide middle dosage with
There was no significant difference between high dose.The above result shows that DHNB contracting phenyl thiosemicarbazide imitates the inhibition of mice serum XOD
Fruit is significant, and has dosage correlation, and DHNB contracting phenyl thiosemicarbazide middle dosage aggregate level is best.
3.2.2 effect of the DHNB contracting phenyl thiosemicarbazide to high lithemia model mice blood uric acid
Mouse detects physiological saline group, high lithemia model group, low dose of DHNB contracting phenyl thiosemicarbazide after high lithemia modeling
Amount group, DHNB contracting phenyl thiosemicarbazide middle dose group, DHNB contracting phenyl thiosemicarbazide high dose group and allopurinol group mouse blood
Clear uric acid level.As shown in fig. 6, model group mice serum content and saline control group show extremely significant sex differernce, table
Bright experiment modeling success.DHNB contracting phenyl thiosemicarbazide and positive drug allopurinol can reduce mice serum uric acid level, and
There is significant difference compared with model group.Compared with positive drug allopurinol, mice serum uric acid level is in DHNB contracting phenyl
It is lower after thiosemicarbazides administration.
As shown in fig. 7, the DHNB contracting phenyl thiosemicarbazide of various dose is to mice serum uric acid compared with allopurinol group
Reducing effect it is more preferable, and show extremely significant level.In addition, the DHNB contracting phenyl thiosemicarbazide of various dose is to mouse blood
The influence of clear uric acid level is different, and the effect of DHNB contracting phenyl thiosemicarbazide middle dosage and high dose is more preferable, has between low dosage
There is significant difference, but drug effect is suitable between middle high dose, without significant difference.The above result shows that DHNB contracting phenyl amino
Thiocarbamide has the function of preferably reducing mice serum uric acid level, and, overall merit more preferable than the effect of positive drug allopurinol
It is best with DHNB contracting phenyl thiosemicarbazide middle dosage.
3.2.3 inhibiting effect of the DHNB contracting phenyl thiosemicarbazide to high lithemia model mice liver XOD vigor
Using phosphotungstic acid method detection physiological saline group, high lithemia model group, DHNB contracting phenyl thiosemicarbazide low dose group,
DHNB contracting phenyl thiosemicarbazide middle dose group, DHNB contracting phenyl thiosemicarbazide high dose group and allopurinol group mouse liver XOD
Vigor shows to test modeling success as shown in figure 8, the vigor of model group XOD enhances compared with saline control group.Modeling
Afterwards, DHNB contracting phenyl thiosemicarbazide and positive drug allopurinol can inhibit mouse liver XOD vigor.In addition, DHNB contracting phenyl
Thiosemicarbazides is slightly stronger than allopurinol to the inhibiting effect of XOD, but there was no significant difference between the two.The above result shows that
DHNB contracting phenyl thiosemicarbazide has good inhibiting effect to mouse liver XOD vigor.
4.DHNB contracting phenyl thiosemicarbazide studies animal toxicity
The poisoning experiment of 4.1 chmice acutes
Choose healthy Kunming mouse 24 (32 ± 2g), half male and half female is divided to two groups, DHNB contracting phenyl thiosemicarbazide group,
Allopurinol group, every group 12, half male and half female is observed after administration by weight quality the stomach-filling of 500mg/kg dosage (ig) single administration
Record mouse behavior, death condition.As a result, mouse non-toxic reaction in one week is administered in DHNB contracting phenyl thiosemicarbazide group, none
Death, it is in good condition；And 12 mouse of Allopurinol group, 6 in the dust, wherein female mice 4, male white mouse 2.Preliminary toxicity examination
It tests and shows that DHNB contracting phenyl thiosemicarbazide toxicity is very low or nontoxic.
Above-described embodiment is only more excellent embodiment of the invention, is implemented according to the technical essence of the invention to above
Any simple modification, modification and the alternate variation that example is made, belong in the range of technical solution of the present invention.
Claims (7)
1. a kind of chemical synthetic drug DHNB contracting phenyl thiosemicarbazide, which is characterized in that structure is as follows:
2. a kind of preparation method of chemical synthetic drug DHNB contracting phenyl thiosemicarbazide as described in claim 1, feature exist
In, with 3,4- dihydroxy -5- nitrobenzaldehyde (DHNB) shown in structural formula (I) be raw material, in solvent methanol with structural formula
(II) 4- phenyl thiosemicarbazide shown in carries out condensation reaction, DHNB contracting phenyl amino shown in composite structure formula (III) through aldehyde amine
Thiocarbamide, wherein 3,4- dihydroxy -5- nitrobenzaldehyde (DHNB) shown in structural formula (I) and 4- benzene shown in structural formula (II)
The molar ratio of base thiosemicarbazides is 1.0~1.05:1；The reaction equation of the above process is as follows.
3. a kind of purposes of chemical synthetic drug DHNB contracting phenyl thiosemicarbazide as described in claim 1, which is characterized in that answer
For preventing, treating gout and hyperuricemia.
4. a kind of purposes of chemical synthetic drug DHNB contracting phenyl thiosemicarbazide according to claim 3, which is characterized in that
The DHNB contracting phenyl thiosemicarbazide is configured to tablet, capsule, granula, injection, liposome as active pharmaceutical ingredient or delays
Release controlled release preparation.
5. a kind of purposes of chemical synthetic drug DHNB contracting phenyl thiosemicarbazide according to claim 3, which is characterized in that
It is used in combination with allopurinol, Febuxostat or colchicin.
6. a kind of purposes of chemical synthetic drug DHNB contracting phenyl thiosemicarbazide according to claim 3, which is characterized in that
Corresponding metal complex is formed with metal ion-chelant.
7. a kind of purposes of chemical synthetic drug DHNB contracting phenyl thiosemicarbazide according to claim 3, which is characterized in that
The DHNB contracting phenyl thiosemicarbazide is as additive application in health food or feed.
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| MENGRONG LI 等: "Investigation of the interaction between benzaldehyde thiosemicarbazone compounds and xanthine oxidase", 《JOURNAL OF MOLECULAR STRUCTURE》 * |
| MING-XUE LI 等: "Synthesis, crystal structures, and biological activities of 2-thiophene N(4)-methylthiosemicarbazone and its unusual hexanuclear silver(I) cluster", 《INORGANIC CHEMISTRY COMMUNICATIONS》 * |
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| Publication number | Publication date |
|---|---|
| CN109336800B (en) | 2022-11-29 |
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