CN104193717B - The preparation method and applications of genistein derivative containing phenylpiperazine - Google Patents
The preparation method and applications of genistein derivative containing phenylpiperazine Download PDFInfo
- Publication number
- CN104193717B CN104193717B CN201410496784.1A CN201410496784A CN104193717B CN 104193717 B CN104193717 B CN 104193717B CN 201410496784 A CN201410496784 A CN 201410496784A CN 104193717 B CN104193717 B CN 104193717B
- Authority
- CN
- China
- Prior art keywords
- genistein
- phenylpiperazine
- derivative containing
- genistein derivative
- containing phenylpiperazine
- 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.)
- Active
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/22—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4
- C07D311/26—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3
- C07D311/34—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3 with aromatic rings attached in position 3 only
- C07D311/36—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3 with aromatic rings attached in position 3 only not hydrogenated in the hetero ring, e.g. isoflavones
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The genistein derivative containing phenylpiperazine is prepared it is an object of the invention to provide a kind of, it has antimicrobial antiphlogistic active, and for preparing the functional food or medicine of protection mucosal lesion, invention also provides preparation method and use.Genistein derivative of the present invention containing phenylpiperazine, its structural formula are as follows：
Description
Technical field
The present invention relates to the genistein derivative preparation method and applications containing phenylpiperazine, belong to organic synthesis technology
Field.
Background technology
With the quickening of modern society's life rhythm, the pressure that people bear society, psychology and work increasing causes
The incidence of stomach lining disease accordingly increases.And allegro life style, nervous working and learning, and excessive drinking etc.
It is then the common cause for causing mucosal lesion.As a kind of worldwide disease, no matter in developed country, or in development China
Family, its incidence of disease are all high.It is reported that in Chinese society population, the people more than 10% suffers from gastric ulcer, and about 25% people suffers from
There are various gastritis, national patients with gastric disease total number of persons nearly 300,000,000 people.Therefore, the work(of high efficiency, low side effects of mucosal lesion is found
The energy property food factor or drug ingedient turn into an important and urgent task.
Genistein is closely related with human health, has many physiological functions, such as anti-oxidant, antitumor action, to blood
The protective action of pipe, improve immunity and antibacterial and anti-inflammation functions etc..Recent someone reports that piperazine also has certain antimicrobial antiphlogistic
Activity.Therefore, piperazine is introduced genistein by the present invention, prepares the genistein derivative containing piperazine.
This analog derivative has protection activity to mucosal lesion, and therefore, genistein derivative is as very promising stomach
Mucosa injury has the functional food factor of protection activity or the prospect of medicine extremely to merit attention.With genistein class medicine
Research deepens continuously, and is carried out on the basis of the mechanism of action for having protection activity to its mucosal lesion constantly understands effective
Structure of modification and modification and MOLECULE DESIGN, it will have increasing efficient, low toxicity genistein class mucosal lesion protection
The functional food factor or medicine of activity are used for clinic, promote the well-being of mankind.
The content of the invention
The genistein derivative containing phenylpiperazine is prepared it is an object of the invention to provide a kind of, it has antimicrobial antiphlogistic
Activity, for preparing the functional food or medicine of protection mucosal lesion, invention also provides its preparation method and use
On the way.
Genistein derivative of the present invention containing phenylpiperazine, its structural formula are as follows：
。
The preparation method of the described genistein derivative containing phenylpiperazine, comprises the following steps：
（1）Genistein, absolute ethyl alcohol, formalin are pressed into quality:Volume:Volume ratio=270:25:0.08~270:
30:0.1 mixing is placed in vessel in heating to 58 ± 3 DEG C, after reaction solution clarification, adds the 1- of 1 ~ 1.1 times of genistein mol ratio
Phenylpiperazine；
（2）Rotor is put into container, is sealed, is placed it on magnetic stirring apparatus and be stirred, reacted at 23 ± 3 DEG C；
（3）After reaction 72 hours, reaction terminates, and has solid precipitation, and filtering, solid is through ethanol: dichloromethane=1: 4 it is mixed
Solution recrystallization is closed, isolates and purifies, obtains target compound.
The purposes of the described genistein derivative containing phenylpiperazine is the function for preparing protection mucosal lesion
Property food or medicine.
In use, mixture is made in the genistein derivative containing phenylpiperazine and sodium carboxymethylcellulose, containing phenyl
The genistein derivative dosage of piperazine accounts for the 1.42-59% of mixture gross mass.
Genistein derivative containing phenylpiperazine can also be dissolved in 0.5-1wt.% sodium carboxymethyl cellulose solutions
In, the concentration of the genistein derivative containing phenylpiperazine is 0.144-14.4mg/mL.
Synthetic route is as follows：
Beneficial effects of the present invention are as follows：
Genistein derivative of the present invention containing phenylpiperazine has protection activity to mucosal lesion, of the invention
Genistein derivative containing phenylpiperazine can be used for the functional food or medicine for preparing protection mucosal lesion.It is prepared
Method is simple and easy, is easily achieved.
Embodiment
The present invention is described further with reference to embodiments.
Embodiment 1
One genistein derivative containing phenylpiperazine：5,7- dihydroxy -3- (4- hydroxyphenyls) -8- ((4- phenyl piperazines
Piperazine -1-yl) methyl) -4H- chroman-4-ons (target compound) preparation.
Genistein 270mg, the mL of absolute ethyl alcohol 25,37% formalin 0.08 are added in 50 mL round-bottomed flasks
mL；58 ± 3 DEG C are heated to, after reaction solution clarification, adds the μ L of 1-php 153；Magnetic agitation reaction is 72 small at room temperature
When, detect reaction process using thin-layer chromatography.After reaction terminates, the solid of precipitation is filtered, solid is through ethanol: dichloromethane=1: 4
Recrystallization separates to obtain target compound；Target compound is mixed with sodium carboxymethylcellulose, object mass ratio in mixture
Example is 1.42%, can be as the functional food or medicine of protection mucosal lesion；Target compound is dissolved in 0.5% carboxymethyl fibre
Tie up in plain sodium solution, the concentration of target compound is 0.144mg/mL in solution, can be as the feature of protection mucosal lesion
Food or medicine.
213.8-214.7 DEG C of fusing point；1H NMR(400 MHz, DMSO-d6)：2.65-2.75 (m, 5H)；3.12-
3.21 (m, 4H)；3.81- 3.89 (m, 3H)；6.22-6.29 (m, 1H)；6.78-6.86(m, 3H)；6.91-6.98
(m, 2H)；7.18-7.27 (m, 2H)；7.36-7.42(m, 2H)；8.39-8.43 (m, 1H).MS (ESI)：444.47
(C26H25N2O5, [M+H]+)。Anal.Calcd for C26H24N2O5：C：70.25%；H：5.44%；N：6.30%；O：18.00%.
Found：C：70.85%；H：4.94%；N：6.95%；O：17.25%.
Embodiment 2
One genistein derivative containing phenylpiperazine：5,7- dihydroxy -3- (4- hydroxyphenyls) -8- ((4- phenyl piperazines
Piperazine -1-yl) methyl) -4H- chroman-4-ons (target compound) preparation.
Genistein 270mg, absolute ethyl alcohol 30 mL, 37% mL of formalin 0.1 are added in 50 mL round-bottomed flasks；
58 ± 3 DEG C are heated to, after reaction solution clarification, adds the μ L of 1-php 168；Magnetic agitation reacts 72 hours at room temperature.
After reaction terminates, the solid of precipitation is filtered, solid is through ethanol: dichloromethane=1: 4 recrystallizations separate to obtain target compound；By mesh
Mark compound mixes with sodium carboxymethylcellulose, and object mass ratio is 59% in mixture, can be used as protection mucosal lesion
Functional food or medicine；Target compound is dissolved in 1% carboxymethylcellulose sodium solution, target compound in solution
Concentration is 14.4mg/mL, can be as the functional food or medicine of protection mucosal lesion.
Target compound physicochemical property and1The data consistent with Example such as H NMR 1.
Embodiment 3
Genistein derivative protection mucosal lesion activity research containing phenylpiperazine：
1. experiment material and method
1.1 medicines and reagent
70% ethanol, CMC（Sodium carboxymethylcellulose）Etc. being that AR, ranitidine are purchased from Hong Rentang pharmacy, close
Into example 1 in target compound.
1.2 animal
SD rat 100-200g, male, purchased from Shandong, animal productiong licensing SCXK (Shandong) 20130001.
1.3 experimental method
1.3.1 animal packet is prepared by model
Animal is randomly divided into six groups, every group of 8 rats, 25 DEG C, 70% humidity.
Treatment group and experimental protocol are as follows in detail：
（1）Reagent controls group：0th, 24,48,49 hours gavage 0.5%CMC 1mL, kill rat in 50 hours.
（2）Ethanol group：0th, 24,48 hours gavage 0.5%CMC 1mL, the 49 hours ethanol of gavage 70%, dosage 2mL/
1000g rat body weights.Kill rat within 50 hours.
（3）Positive drug group：0th, 24,48 hours gavage ranitidines (50 mg/1000g rat body weights), 49 hours gavages
70% ethanol, dosage are 2mL/1000g rat body weights.Kill rat within 50 hours.
（4）Target compound low dose group：0th, once, dosage is 0.45 mg/ to 24,48 hours gavage target compounds
1000g rat body weights, 49 hours oral 70% ethanol, dosage are 2 mL/1000g rat body weights, kill rat within 50 hours.
（5）Target compound middle dose group：0th, once, dosage is 4.5 mg/ to 24,48 hours gavage target compounds
1000g rat body weights, 49 hours oral 70% ethanol, dosage are 2 mL/1000g rat body weights, kill rat within 50 hours.
（6）Target compound high dose group：0th, once, dosage is 45 mg/1000g to 24,48 hours gavage target compounds
Rat body weight, 49 hours oral 70% ethanol, dosage are 2 mL/1000g rat body weights, kill rat within 50 hours.
1.3.2 gastric mucosal damage index and mucosal lesion inhibiting rate calculate
Put to death rat and take gastric mucosa tissue, with the naked eye with the degree of impairment of amplification sem observation stomach lining, commented with reference to Guth
Minute mark is accurate, calculates gastric mucosal damage index, and it is 1 point that point-like damage or damage, which are less than 1 mm, and the mm of wire damaged length 1~2 is 2
Point, the mm of wire damaged length 2~3 is 3 points, and the mm of wire damaged length 3~4 is 4 points, and by that analogy, wherein lesion width is big
Being doubled in 2 mm score values, all score sums are gastric mucosal damage index, mucosal lesion inhibiting rate=（Model group damage refers to
Number-administration group damage index）/ model group damage index × 100%
2. experimental result
Inhibiting rate of the target compound to mucosal lesion listed by the present invention of table 1
| Sample | Inhibiting rate（%） |
| Positive drug group | 72.5±2.6 |
| Target compound low dose group | 31.4±3.4 |
| Target compound middle dose group | 52.9±5.9 |
| Target compound high dose group | 88.2±4.7 |
From table 1, when target compound dosage is respectively 0.9%, 9% and the 90% of control drug group dosage, inhibiting rate point
Not Wei control drug group 43.3%, 73.0% and 122%.It can be seen that the effect of target compound is better than positive drug effect.
Claims (5)
1. a kind of genistein derivative containing phenylpiperazine, it is characterised in that its structural formula is as follows：
。
A kind of 2. preparation method of the genistein derivative containing phenylpiperazine described in claim 1, it is characterised in that bag
Include following steps：
（1）Genistein, absolute ethyl alcohol, formalin are pressed into quality:Volume:Volume ratio=270:25:0.08~270:30:
0.1 mixing is placed in vessel in heating to 58 ± 3 DEG C, after reaction solution clarification, adds the 1- phenyl of 1 ~ 1.1 times of genistein mol ratio
Piperazine；
（2）Rotor is put into container, is sealed, is placed it on magnetic stirring apparatus and be stirred, reacted at 23 ± 3 DEG C；
（3）After reaction 72 hours, reaction terminates, and has solid precipitation, and filtering, solid is through ethanol:Dichloromethane=1:4 mixing is molten
Liquid recrystallizes, and isolates and purifies, obtains target compound.
A kind of 3. purposes of the genistein derivative containing phenylpiperazine described in claim 1, it is characterised in that：For preparing
The functional food or medicine of auxiliary protection mucosal lesion.
4. the purposes of the genistein derivative containing phenylpiperazine according to claim 3, it is characterised in that：Benzene will be contained
The genistein derivative of base piperazine is dissolved in 0.5-1wt.% sodium carboxymethyl cellulose solutions, the dyewood containing phenylpiperazine
The concentration of plain derivative is 0.144-14.4mg/mL.
5. a kind of its synthetic route of the genistein derivative containing phenylpiperazine according to claim 2 is as follows：
。
Its specific preparation method of genistein derivative containing phenylpiperazine is as claimed in claim 2.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410496784.1A CN104193717B (en) | 2014-09-25 | 2014-09-25 | The preparation method and applications of genistein derivative containing phenylpiperazine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410496784.1A CN104193717B (en) | 2014-09-25 | 2014-09-25 | The preparation method and applications of genistein derivative containing phenylpiperazine |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN104193717A CN104193717A (en) | 2014-12-10 |
| CN104193717B true CN104193717B (en) | 2018-02-02 |
Family
ID=52079125
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410496784.1A Active CN104193717B (en) | 2014-09-25 | 2014-09-25 | The preparation method and applications of genistein derivative containing phenylpiperazine |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104193717B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NL2031294B1 (en) * | 2021-12-30 | 2023-07-05 | Univ Shandong Technology | Preparation method and application of genistein derivative containing benzylpiperazine |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1603318A (en) * | 2004-07-05 | 2005-04-06 | 南京大学 | Genistein derivatives and their preparation process and use |
| CN101012213A (en) * | 2006-12-22 | 2007-08-08 | 南京大学 | Derivative of genistein and its preparing method and use |
| CN102659742A (en) * | 2012-05-29 | 2012-09-12 | 南京大学 | Application of genistein derivative in preparing medicament for treating learning and memory disorder |
-
2014
- 2014-09-25 CN CN201410496784.1A patent/CN104193717B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1603318A (en) * | 2004-07-05 | 2005-04-06 | 南京大学 | Genistein derivatives and their preparation process and use |
| CN101012213A (en) * | 2006-12-22 | 2007-08-08 | 南京大学 | Derivative of genistein and its preparing method and use |
| CN102659742A (en) * | 2012-05-29 | 2012-09-12 | 南京大学 | Application of genistein derivative in preparing medicament for treating learning and memory disorder |
Non-Patent Citations (3)
| Title |
|---|
| 染料木素的研究进展;张萍、郑万金、仲英;《齐鲁药事》;20080520;第27卷(第2期);第103-107页 * |
| 染料木素结构修饰及其抗氧化活性构效关系的研究;陈传平；陈乃东；葛飞飞;《安徽农业科学》;20131231;第41卷(第16期);第7061-7065页 * |
| 染料木素结构修饰研究进展;王秋亚；高锦红;《广州化工》;20110307;第38卷(第11期);第25-27页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN104193717A (en) | 2014-12-10 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102234259A (en) | Sphaelactone derivatives, their pharmaceutical compositions, preparation method thereof and application thereof | |
| CN104311519B (en) | Functional food factor preparation and its application with mucosal lesion protective effect | |
| JP4286238B2 (en) | Bacthiol-containing pharmaceutical composition | |
| CN104292199B (en) | Genistein derivative preparation method containing benzyl diethylenediamine and its to gastric mucosal protection application | |
| CN101965185A (en) | Use of tea polyphenols in preparing medicaments for prevention or treatment of tumors | |
| CN104193717B (en) | The preparation method and applications of genistein derivative containing phenylpiperazine | |
| CN102166260B (en) | Clove extract with tumor resisting effect and pharmaceutical preparation thereof | |
| CN102234258B (en) | Preparation method and application of sphaelactone | |
| CN104274455B (en) | The preparation method of quercetin derivative containing benzyl diethylenediamine and its to the protective effects on gastric mucosa | |
| CN102010398B (en) | Nitrogen-containing biphenyl compound, pharmaceutical composition containing compound, preparation methods and application of compound in HIV-1 resistance | |
| CN101792401B (en) | Biphenyl compound with anti-tumor activity and preparation method thereof | |
| CN106554339A (en) | A kind of isoflavone derivative and its production and use | |
| WO2008148269A1 (en) | Anti-tumor medicine containing betulinic acid derivatives | |
| CN101239964B (en) | 15-oxospiramilactone and its medicament composition, preparation method and application | |
| JP4286237B2 (en) | Bacthiol-containing pharmaceutical composition | |
| CN101569654B (en) | Application of pigeon pea stilbene acid in the preparation of antitumor drug | |
| CN1178118A (en) | External use disinfectant anagesic and production thereof | |
| CN109053770A (en) | A kind of 1,4- sulphur azatropylidene medicinal compound and its preparation method and application for skin ulcer nursing | |
| CN102309487A (en) | The antihepatocarcinoma effect of piperine and pharmaceutical preparation thereof | |
| CN108785383A (en) | A kind of antibacterial gynecology externally used pharmaceutical combination and the preparation method and application thereof | |
| NL2031294B1 (en) | Preparation method and application of genistein derivative containing benzylpiperazine | |
| CN102584846A (en) | Curcumenol derivatives resisting influenza A(H1N1) virus | |
| CN105055471A (en) | Application of radix bupleuri total saponin and monomer saponin thereof in pharmacy | |
| CN102106858A (en) | Anti-cervical carcinoma effect of maslinic acid and medicinal preparation thereof | |
| CN102309484A (en) | The effect of anti-lung cancer of piperine and pharmaceutical preparation 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 | ||
| CB03 | Change of inventor or designer information |
Inventor after: Zhou Quancheng Inventor after: Su Xinyong Inventor after: Feng Chuanxing Inventor after: Wang Qi Inventor after: Li Hui Inventor after: Wang Meng Inventor before: Zhou Quancheng Inventor before: Zhu Hailiang Inventor before: Chen Xiangfei Inventor before: Feng Chuanxing Inventor before: Zhang Guangyao Inventor before: Lu Hao Inventor before: Chang Xuan |
|
| CB03 | Change of inventor or designer information | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |