CN112574160B - Galangin derivative and preparation method and application thereof - Google Patents
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Abstract
The invention discloses a galangin derivative and a preparation method and application thereof, wherein the galangin derivative is a compound with a structure shown as a general formula I, a stereoisomer, a hydrate, an ester, a solvate, a co-crystal, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof; wherein R is-NH 2 、‑N(CH 3 ) 2 、‑NHCH 3 、
Or
According to the invention, a series of galangin derivatives are prepared by carrying out structural modification on galangin; most of the galangin derivatives prepared by the invention have stronger uric acid reducing effect than galangin.
Description
Technical Field
The invention belongs to the technical field of pharmacy, and particularly relates to a galangin derivative and a preparation method and application thereof.
Background
With the improvement of living standard and the change of eating habit of people, the incidence of hyperuricemia and gout in China is on a rising trend year by year in recent years. Hyperuricemia is a disease in which blood uric acid exceeds normal values due to purine metabolic disorder and/or uric acid excretion disorder, and means 2 times of fasting blood uric acid levels on the same day under a normal purine diet: >420 μmol/L in males and >360 μmol/L in females, without clinically exhibiting any symptoms. When a human body is in hyperuricemia for a long time, uric acid is precipitated in joints, soft tissues, cartilages and kidneys in the form of sodium salt, so that organ and tissue diseases of the human body are caused, gout is caused, serious complications are caused, the symptoms comprise gouty arthritis, gouty kidney diseases, gouty kidney stones, gouty heart diseases, gouty hypertension and the like, and patients have symptoms of arthralgia, renal colic or hematuria and the like.
At present, the clinical medicine for treating hyperuricemia is mainly western medicine, has obvious curative effect, but has a plurality of adverse reactions, such as gastrointestinal symptoms, rash, liver function damage, bone marrow suppression and the like, and damages the health of a human body in the treatment process; for example, Allopurinol (Allopurinol) is a drug widely used for reducing uric acid, and has the effect of reducing uric acid by inhibiting uric acid synthesis, but adverse reactions caused by Allopurinol include gastrointestinal symptoms, rash, liver function damage, bone marrow inhibition and the like, and the Allopurinol is monitored. About 5% of patients are intolerant. Occasionally, severe Allopurinol Hypersensitivity Syndrome (AHS) occurs. This risk is increased in patients with renal insufficiency and when thiazide diuretics are used. The relevant literature proves that AHS is closely related to leukocyte antigen HLA-B5801 gene positivity. Although the incidence of AHS is only 0.1%, the mortality rate is as high as 20%. Therefore, the medicament for reducing the uric acid is developed, has safety, effectiveness and lower toxic and side effects, has extremely wide market prospect, and can create good social and economic benefits. In recent years, it has been found that galangin has a significant xanthine oxidase inhibitory effect in vivo and in vitro, can be used for the treatment of hyperuricemia, and has less toxic and side effects, but the 7-hydroxy group of galangin is easily metabolized in vivo, and thus bioavailability is not high.
Disclosure of Invention
The invention aims to overcome the defects of the prior art, provides a galangin derivative, a preparation method and application thereof, and can expand and obtain a novel efficient uric acid reducing medicament.
In order to achieve the above objects, a first aspect of the present invention provides a galangin derivative, which is a compound having a structure represented by general formula i, a stereoisomer, a hydrate, an ester, a solvate, a co-crystal, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof;
wherein R is-NH 2 、-N(CH 3 ) 2 、-NHCH 3 、
In the invention, the galangin is structurally modified by the inventor to obtain a series of galangin amide derivatives, wherein some compounds have higher in vivo activity and are obviously improved.
According to the present invention, preferably, the galangin derivative is at least one selected from the group consisting of compounds represented by structural formulae GAL-001 to GAL-006;
a second aspect of the present invention provides a method for producing the galangin derivative, the method comprising:
(1) in the presence of a first organic solvent and an acid-binding agent, carrying out contact reaction on a compound shown as a formula II and a compound shown as a formula III to obtain a compound shown as a formula IV;
(2) in the presence of a second organic solvent, carrying out hydrolysis reaction on the compound shown in the formula IV and an alkali solution to obtain the galangin derivative;
wherein, in the formulas III and IV, R is-NH 2 、-N(CH 3 ) 2 、-NHCH 3 、
The preparation method of the galangin derivative is shown as a reaction equation 1;
according to the present invention, preferably, in step (1), the first organic solvent is at least one of acetonitrile, acetone, butanone and DMF;
the acid-binding agent is sodium carbonate and/or potassium carbonate.
In the present invention, the sodium carbonate and/or potassium carbonate is preferably anhydrous sodium carbonate and/or anhydrous potassium carbonate.
According to the present invention, preferably, in the step (2), the second organic solvent is at least one of methanol, ethanol and THF;
the alkali solution is sodium hydroxide aqueous solution and/or potassium hydroxide aqueous solution.
The third aspect of the present invention provides the use of the galangin derivative described above in the preparation of a medicament for the treatment of hyperuricemia.
The technical scheme of the invention has the following beneficial effects:
according to the invention, a series of galangin derivatives are prepared by carrying out structural modification on galangin; most of the galangin derivatives prepared by the invention have stronger uric acid reducing effect than galangin.
Additional features and advantages of the invention will be set forth in the detailed description which follows.
Detailed Description
Preferred embodiments of the present invention will be described in more detail below. While the following describes preferred embodiments of the present invention, it should be understood that the present invention may be embodied in various forms and should not be limited by the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the scope of the invention to those skilled in the art.
In the following examples, 3, 5-diacetoxy-7-hydroxyflavone was purchased from Wuhan Ying Rui pharmaceutical science, Inc.
Example 1
Adding 354mg of 3, 5-diacetoxy-7-hydroxyflavone (compound shown in formula II), 200ml of anhydrous butanone, 0.2g of anhydrous potassium carbonate and 302mg of 3-bromopropionamide (compound shown in formula III) into a reaction bottle, heating and refluxing, detecting by TLC until a raw material point disappears, filtering to remove the potassium carbonate, recovering the solvent, adding 200ml of methanol and 10ml of 40% sodium hydroxide aqueous solution, heating to 50 ℃ until the TLC detects complete hydrolysis, cooling, adjusting the pH to 4-5 by hydrochloric acid, recovering the solvent, adding water, extracting by ethyl acetate, and performing 200-mesh and 300-mesh silica gel column chromatography to obtain a yellow solid (compound shown in formula I, wherein R is-NH, and the structure is-NH 2 ). The spectrum analysis and verification are carried out on the product, and the data are as follows:
1 H NMR(400MHz,DMSO-d 6 )12.37(1H,s),10.56(1H,s),9.67(1H,s),8.12(2H,m),7.57(2H,m)，7.46(1H,m)，6.32(1H,d,J＝2.0Hz),6.27(1H,d,J＝2.0Hz),3.87(2H,t),2.64(2H,t),-ESI 340.1
example 2
Adding 354mg of 3, 5-diacetoxy-7-hydroxyflavone (compound shown in formula II), 200ml of acetonitrile, 0.3g of anhydrous potassium carbonate and 332mg of N-methyl-3-bromopropionamide (compound shown in formula III) into a reaction bottle, heating and refluxing, detecting by TLC until a raw material point disappears, filtering to remove the potassium carbonate, recovering the solvent, adding 200ml of methanol and 10ml of 40% sodium hydroxide aqueous solution, heating to 50 ℃ until the TLC detects complete hydrolysis, cooling, adjusting the pH to 4-5 by hydrochloric acid, recovering the solvent, adding water, extracting by ethyl acetate, and performing 200-mesh 300-mesh silica gel column chromatography to obtain a yellow solid (compound shown in formula I, wherein R is-NHCH 3 ). The spectrum analysis and verification are carried out on the product, and the data are as follows:
1 H NMR(400MHz,DMSO-d 6 )12.36(1H,s),10.58(1H,s),9.67(1H,s),8.09(2H,m),7.58(2H,m)，7.46(1H,m)，6.32(1H,d,J＝2.0Hz),6.25(1H,d,J＝2.0Hz),3.81(2H,t),2.65(2H,t),2.43(3H,s)-ESI 354.3
example 3
Adding 354mg of 3, 5-diacetoxy-7-hydroxyflavone (compound shown in formula II), 200ml of acetonitrile, 0.3g of anhydrous potassium carbonate and 360mg of N, N-dimethyl-3-bromopropionamide (compound shown in formula III) into a reaction bottle, heating and refluxing, detecting by TLC until a raw material point disappears, filtering to remove the potassium carbonate, recovering the solvent, adding 200ml of methanol and 10ml of sodium hydroxide aqueous solution with the mass concentration of 40%, heating to 50 ℃ until the TLC detects complete hydrolysis, cooling, adjusting the pH to 4-5 by hydrochloric acid, recovering the solvent, adding water, extracting by ethyl acetate, and performing 200-mesh 300-mesh silica gel column chromatography to obtain a yellow solid (compound shown in formula I, wherein R is-N (CH) and R is-N (compound shown in formula I) 3 ) 2 ). The spectrum analysis and verification are carried out on the product, and the data are as follows:
1 H NMR(400MHz,DMSO-d 6 )12.35(1H,s),10.59(1H,s),9.63(1H,s),8.11(2H,m),7.46(2H,m)，7.37(1H,m)，6.41(1H,d,J＝2.0Hz),6.18(1H,d,J＝2.0Hz),3.85(2H,t),2.63(2H,t),2.45(6H,s)-ESI 368.1
example 4
Adding 354mg of 3, 5-diacetoxy-7-hydroxyflavone (compound shown in formula II), 200ml of butanone, 0.3g of anhydrous potassium carbonate and 412mg of 1- (3-bromopropionyl) pyrrolidine (compound shown in formula III) into a reaction bottle, heating for reflux, detecting by TLC until a raw material point disappears, filtering to remove the potassium carbonate, recovering the solvent, adding 200ml of ethanol and 10ml of sodium hydroxide aqueous solution with the mass concentration of 40%, heating at 50 ℃ until the TLC detects that the hydrolysis is complete, cooling, adjusting the pH to 4-5 by hydrochloric acid, recovering the solvent, adding water, extracting by ethyl acetate, and performing 200-mesh 300-mesh silica gel column chromatography to obtain a yellow solid (compound shown in formula I, wherein R is the compound shown in formula I, and R is the compound shown in formula I
). The spectrum analysis and verification are carried out on the product, and the data are as follows:
1 H NMR(400MHz,DMSO-d 6 )12.35(1H,s),10.49(1H,s),9.63(1H,s),8.11(2H,m),7.45(2H,m)，7.32(1H,m)，6.45(1H,d,J＝2.0Hz),6.14(1H,d,J＝2.0Hz),3.87(2H,t),2.65(2H,t),2.47(4H,t)，1.49(4H,m)-ESI 394.2
example 5
Adding 354mg of 3, 5-diacetoxy-7-hydroxyflavone (compound shown in formula II), 200ml of butanone, 0.3g of anhydrous potassium carbonate and 440mg of 1- (3-bromopropionyl) piperidine (compound shown in formula III) into a reaction bottle, heating for reflux, detecting by TLC until a raw material point disappears, filtering to remove the potassium carbonate, recovering the solvent, adding 200ml of ethanol and 10ml of sodium hydroxide aqueous solution with the mass concentration of 40%, heating to 50 ℃ until the TLC detects complete hydrolysis, cooling, adjusting the pH to 4-5 by hydrochloric acid, recovering the solvent, adding water, extracting by ethyl acetate, and performing 200-mesh 300-mesh silica gel column chromatography to obtain a yellow solid (compound shown in formula I, wherein R is a compound shown in formula I, and R is a compound shown in formula I
). The spectrum analysis and verification are carried out on the product, and the data are as follows:
1 H NMR(400MHz,DMSO-d 6 )12.37(1H,s),10.60(1H,s),9.65(1H,s),8.12(2H,m),7.43(2H,m)，7.41(1H,m)，6.45(1H,d,J＝2.0Hz),6.22(1H,d,J＝2.0Hz),3.84(2H,t),2.65(2H,t),2.48(4H,t)，1.47(6H,m)-ESI 408.2
example 6
Adding 354mg of 3, 5-diacetoxy-7-hydroxyflavone (compound shown in formula II), 200ml of butanone, 0.3g of anhydrous potassium carbonate and 444mg of 4- (3-bromopropionyl) morpholine (compound shown in formula III) into a reaction bottle, heating for reflux, detecting by TLC until a raw material point disappears, filtering to remove the potassium carbonate, recovering the solvent, adding 200ml of ethanol and 10ml of sodium hydroxide aqueous solution with the mass concentration of 40%, heating to 50 ℃ until the TLC detects complete hydrolysis, cooling, adjusting the pH to 4-5 by hydrochloric acid, recovering the solvent, adding water, extracting by ethyl acetate, and performing 200-mesh 300-mesh silica gel column chromatography to obtain a yellow solid (compound shown in formula I, wherein R is a compound shown in formula I, and R is a compound shown in formula I
). The spectrum analysis and verification are carried out on the test piece, and the data are as follows:
1 H NMR(400MHz,DMSO-d 6 )12.34(1H,s),10.45(1H,s),9.67(1H,s),8.13(2H,m),7.42(2H,m)，7.35(1H,m)，6.47(1H,d,J＝2.0Hz),6.15(1H,d,J＝2.0Hz),3.89(2H,t),3.75(4H,t)2.67(2H,t)2.45(4H,t)，-ESI 410.3
test example
Data of drug effect experiment
This test example compares the effect of the compound on uric acid lowering activity with allopurinol as a positive control.
(1) Weighing a proper amount of oteracil potassium, suspending with 0.5% CMC-Na aqueous solution by mass concentration, and preparing into 12.5mg/mL molding solution.
(2) 100 test mice (Kunming mice, male mice) were divided into 10 groups at random according to body weight, and 10 mice were each divided into a blank control group, a model control group, an allopurinol group, and a galangin group, respectively, in example 1, example 2, example 3, example 4, example 5, and example 6,
day 1-5: the test mice are raised indoors in cages at room temperature (20-22 ℃), with relative humidity of 35-50%, and are fed with free diet and drinking water for 5 days;
day 6-11:
feeding 0.2ml/10g of CMC-Na aqueous solution with the mass concentration of 0.5 percent to mice of a blank control group and a model control group by intragastric administration every day;
feeding allopurinol to allopurinol group mice by intragastric administration every day, wherein the administration dose is 10mg/kg once a day;
the mice of other administration groups are subjected to intragastric administration of each compound, and the administration dose is 10mg/kg once a day;
day 12:
injecting 0.2mL/10g CMC-Na aqueous solution with the mass concentration of 0.5% into the abdominal cavity of the empty and white control group mouse;
the abdominal cavities of mice in a model control group, an allopurinol group, a galangin group, an example 1 group, an example 2 group, an example 3 group, an example 4 group, an example 5 group and an example 6 group are respectively injected with 0.2mL/10g of the molding solution prepared in the step (1);
after 1 hour of drug injection into mice in the blank control group, model control group, allopurinol group, and galangin group, examples 1 group, 2 group, 3 group, 4 group, 5 group, and 6 group, the eyes were removed and blood was collected, and the above samples were collectedAdding a reaction reagent according to a uric acid determination kit to perform determination. The test data were statistically analyzed by SPSS11.5 software, and the results were analyzed to
And (4) showing. The test results are shown in table 1 below.
TABLE 1
| Group of | Dosage (mg/kg) | Animals (only) | Blood uric acid (mu mol/L) |
| Blank control group | — | 10 | 205.19±15.20 |
| Model control group | — | 10 | 408.54±15.23 |
| Allopurinol group | 10 | 10 | 207.43±13.11 |
| Galangin group | 10 | 10 | 305.76±24.05 |
| EXAMPLE 1 group | 10 | 10 | 317.08±13.92 |
| EXAMPLE 2 group | 10 | 10 | 286.89±14.35 |
| EXAMPLE 3 group | 10 | 10 | 296.34±15.35 |
| EXAMPLE 4 group | 10 | 10 | 254.73±20.13 |
| EXAMPLE 5 group | 10 | 10 | 265.89±14.35 |
| EXAMPLE 6 group | 10 | 10 | 217.26±15.59 |
As can be seen from table 1, in the groups of examples 1 to 6, except that the effect of the higher galangin in the group of example 1 is reduced, the effect of other compounds is better than that of the higher galangin, wherein the effect of the group of example 6 is equivalent to that of the allopurinol positive drug.
Having described embodiments of the present invention, the foregoing description is intended to be exemplary, not exhaustive, and not limited to the embodiments disclosed. Many modifications and variations will be apparent to those of ordinary skill in the art without departing from the scope and spirit of the described embodiments.
Claims (6)
1. A galangin derivative is characterized in that the galangin derivative is a compound with a structure shown as a general formula I or a pharmaceutically acceptable salt thereof;
wherein R is-NH 2 、-N(CH 3 ) 2 、-NHCH 3 、
2. The galangin derivative according to claim 1, wherein the galangin derivative is at least one selected from the group consisting of compounds represented by structural formulae GAL-001 to GAL-006;
3. the process for producing a galangin derivative according to claim 1 or 2, which comprises:
(1) in the presence of a first organic solvent and an acid-binding agent, carrying out contact reaction on a compound shown as a formula II and a compound shown as a formula III to obtain a compound shown as a formula IV;
(2) in the presence of a second organic solvent, carrying out hydrolysis reaction on the compound shown in the formula IV and an alkali solution to obtain the galangin derivative;
wherein, in the formulas III and IV, R is-NH 2 、-N(CH 3 ) 2 、-NHCH 3 、
4. The production method according to claim 3, wherein in step (1), the first organic solvent is at least one of acetonitrile, acetone, butanone and DMF;
the acid-binding agent is sodium carbonate and/or potassium carbonate.
5. The production method according to claim 3, wherein in step (2), the second organic solvent is at least one of methanol, ethanol, and THF;
the alkali solution is sodium hydroxide aqueous solution and/or potassium hydroxide aqueous solution.
6. Use of a galangin derivative according to claim 1 or 2 for the preparation of a medicament for the treatment of hyperuricemia.
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008040236A1 (en) * | 2006-09-20 | 2008-04-10 | Topharman Shanghai Co., Ltd. | Flavones derivatives, preparation methods and uses thereof |
| US20100310688A1 (en) * | 2009-06-08 | 2010-12-09 | National Taiwan University | acacia extracts and their compounds on inhibition of xanthine oxidase |
| CN102911147A (en) * | 2012-11-01 | 2013-02-06 | 昆明制药集团股份有限公司 | Novel compound, preparation method and application thereof and medicament composition and preparation of novel compound |
| CN103301110A (en) * | 2013-07-02 | 2013-09-18 | 新疆维吾尔自治区维吾尔医药研究所 | Application for galangin derivatives in preparation of medicines for preventing and treating vitiligo |
| CN109761944A (en) * | 2019-02-13 | 2019-05-17 | 武汉翼博济生生物科技有限公司 | A kind of chrysin amide derivatives and preparation method thereof and medical usage |
-
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- 2020-12-07 CN CN202011419886.5A patent/CN112574160B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008040236A1 (en) * | 2006-09-20 | 2008-04-10 | Topharman Shanghai Co., Ltd. | Flavones derivatives, preparation methods and uses thereof |
| US20100310688A1 (en) * | 2009-06-08 | 2010-12-09 | National Taiwan University | acacia extracts and their compounds on inhibition of xanthine oxidase |
| CN102911147A (en) * | 2012-11-01 | 2013-02-06 | 昆明制药集团股份有限公司 | Novel compound, preparation method and application thereof and medicament composition and preparation of novel compound |
| CN103301110A (en) * | 2013-07-02 | 2013-09-18 | 新疆维吾尔自治区维吾尔医药研究所 | Application for galangin derivatives in preparation of medicines for preventing and treating vitiligo |
| CN109761944A (en) * | 2019-02-13 | 2019-05-17 | 武汉翼博济生生物科技有限公司 | A kind of chrysin amide derivatives and preparation method thereof and medical usage |
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