CN111302942B - Compound with PTP1B inhibitory activity and application thereof - Google Patents
Compound with PTP1B inhibitory activity and application thereof Download PDFInfo
- Publication number
- CN111302942B CN111302942B CN202010273869.9A CN202010273869A CN111302942B CN 111302942 B CN111302942 B CN 111302942B CN 202010273869 A CN202010273869 A CN 202010273869A CN 111302942 B CN111302942 B CN 111302942B
- Authority
- CN
- China
- Prior art keywords
- compound
- methanol
- inhibitory activity
- ethyl acetate
- formula
- 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
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/66—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety
- C07C69/73—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of unsaturated acids
- C07C69/732—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of unsaturated acids of unsaturated hydroxy carboxylic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/48—Separation; Purification; Stabilisation; Use of additives
- C07C67/56—Separation; Purification; Stabilisation; Use of additives by solid-liquid treatment; by chemisorption
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/48—Separation; Purification; Stabilisation; Use of additives
- C07C67/58—Separation; Purification; Stabilisation; Use of additives by liquid-liquid treatment
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Diabetes (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Steroid Compounds (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
The invention provides two compounds with PTP1B inhibitory activity, which have a structure shown in formula 1 or formula 2. The invention discloses two hydroquinone-containing heteroterpene compounds discovered from ganoderma tropicalis for the first time. The compounds are found to have obvious PTP1B inhibitory activity through biological activity evaluation, enhance the sensitivity of insulin receptors and have application prospects in development of diabetes drugs.
Description
Technical Field
The invention relates to the technical field of natural medicines, in particular to two compounds with PTP1B inhibitory activity and application thereof.
Background
Diabetes mellitus is a metabolic disease characterized by chronic hyperglycemia due to multiple causes, whether hyperglycemia is caused by defective insulin secretion or impaired biological action, or both. Hyperglycemia occurring in the long term of diabetes results in chronic damage to, and dysfunction of, various tissues, particularly the eyes, kidneys, heart, blood vessels, nerves. Diabetes is one of the most major non-infectious diseases that currently threaten global human health in the world. There are two major types of diabetes, type i diabetes (insulin-dependent) and type II diabetes (non-insulin-dependent), with type II diabetes accounting for more than 90% of the total number of diabetic patients. According to the international diabetes union, there are about 3.7 billion diabetic patients worldwide in 2011 and nearly 5.7 billion diabetic patients worldwide by 2030, 80% of which are in developing countries. The number of the diabetics given by the national health department in 2009 is 9200 ten thousand, the number of the diabetics becomes 1.14 hundred million by 2013, 2200 million diabetics are increased in China in four years, the number of the diabetics is increased by 550 ten thousand per year on average, and the number of the diabetics is increased by 1.5 ten thousand per day. PTP1B is a member of the protein tyrosine phosphatase family, which down-regulates insulin signal transduction by dephosphorylating tyrosine residues on the insulin receptor or its substrate, and is also a potentially important target for the treatment of type II diabetes and obesity.
Disclosure of Invention
In view of the above, the technical problem to be solved by the present invention is to provide two compounds with PTP1B inhibitory activity and their applications, the present invention uses pseudotropical ganoderma lucidum fruiting body as research object, separates and purifies its crude extract to obtain 2 novel hydroquinone heteroterpene compounds, and through biological activity evaluation, the compounds have good PTP1B inhibitory activity, enhance insulin receptor sensitivity, and can be used for developing drugs for treating type II diabetes.
Ganoderma lucidum (Ganoderma ahmadii Steyaret) is medicinal fungus of Ganoderma of Ganodermataceae (Ganoderma). The chemical components of the ganoderma fungus mainly comprise polysaccharide, triterpenes, alkaloid, sterol compounds, polypeptide nucleosides, amino acid, trace elements and the like. The triterpene and polysaccharide are used as main active ingredients, and have effects of resisting tumor, protecting liver, resisting HIV-4 and HIV-4 protease activity, resisting histamine release, inhibiting angiotensin and resisting oxidation. In recent years, the heteroterpenoids discovered from ganoderma are another important active molecule in ganoderma, and have biological activities such as liver protection and allergy resistance.
The invention provides two compounds with PTP1B inhibitory activity, which have a structure shown in formula 1 or formula 2:
the invention provides a preparation method of the compound, which comprises the following steps:
A) extracting the dried fruiting body powder of the Ganoderma tropicalis with ethanol under heating and refluxing to obtain ethanol extractive solution;
B) concentrating the ethanol extract under reduced pressure, adding water for suspension, extracting with ethyl acetate, and distilling and concentrating the extract to obtain ethyl acetate extract;
C) separating the ethyl acetate extract by normal phase silica gel column chromatography to obtain components Fr.1-Fr.7;
d-1) taking Fr.6, inverting C18Performing column chromatography to obtain Fr.6-1-Fr.6-5;
e-1) taking Fr.6-4, and purifying by using semi-preparative high performance liquid chromatography to obtain a compound shown in a formula 1;
d-2) taking Fr.7 and inverting C18Performing column chromatography to obtain Fr.7-1-Fr.7-6;
e-2) taking Fr.7-5, carrying out chromatography by a sephadex column LH-20, and eluting by methanol to obtain Fr.7-5-1-Fr.7-5-5;
f-2) taking Fr.7-5-4, and purifying by semi-preparative high performance liquid chromatography to obtain the compound shown in the formula 2.
The ethanol of step a) is preferably 95% ethanol.
The step B) is preferably as follows:
concentrating the ethanol extract under reduced pressure, adding water for suspension, sequentially extracting with petroleum ether, ethyl acetate and n-butanol, collecting ethyl acetate extract, and distilling and concentrating to obtain ethyl acetate extract.
In the step C), the eluent for normal phase silica gel column chromatography is preferably petroleum ether/ethyl acetate, and the volume ratio of the petroleum ether to the ethyl acetate is 10: 1-1: and 2, performing gradient elution.
In some embodiments of the invention, gradient elution is performed sequentially with a petroleum ether/ethyl acetate system (V: V ═ 10: 1, 8: 1, 6: 1, 4: 1, 2: 1, 1: 1, 1: 2), and the fractions are collected in fractions, and combined after detection by thin layer chromatography to give 7 fractions fr.1 to fr.7.
Fr.6 is taken and subjected to reversed phase C18Column chromatography is carried out to obtain Fr.6-1 to Fr.6-5.
In said step D-1), the phase inversion C18Preferably, the eluent for column chromatography is methanol/water, the volume ratio of the methanol to the water is preferably 30: 1-100: 0, and gradient elution is carried out.
After Fr.6-1-Fr.6-5 is obtained, Fr.6-4 is taken and purified by semi-preparative high performance liquid chromatography to obtain the compound shown in the formula 1, which is recorded as Ganodulariporol F.
The mobile phase of the semi-preparative high performance liquid chromatography is preferably a mixed solvent of acetonitrile and trifluoroacetic acid.
The mobile phase is more preferably V (acetonitrile): V (0.1% aqueous trifluoroacetic acid): 42: 58.
The flow rate of the semi-preparative high performance liquid chromatography mobile phase is preferably 4mL min-1。
Fr.7 is taken and subjected to reversed phase C18Performing column chromatography to obtain Fr.7-1-Fr.7-6.
In the step D-2), the phase inversion C18Preferably, the eluent for column chromatography is methanol/water, the volume ratio of the methanol to the water is preferably 20: 1-100: 0, and gradient elution is carried out.
After Fr.7-1-Fr.7-6 is obtained, Fr.7-5 is taken and chromatographed by sephadex column LH-20 and eluted by methanol to obtain Fr.7-5-1-Fr.7-5-5.
And (5) purifying Fr.7-5-4 by using semi-preparative high performance liquid chromatography to obtain a compound shown as a formula 2, which is recorded as Ganodulariporol G.
The mobile phase of the semi-preparative high performance liquid chromatography is preferably a mixed solvent of methanol and trifluoroacetic acid.
The mobile phase is more preferably V (methanol): V (0.1% aqueous trifluoroacetic acid): 72: 28.
The flow rate of the mobile phase is preferably 4 mL-min-1。
The invention provides the application of the compound with PTP1B inhibitory activity or the compound with PTP1B inhibitory activity prepared by the preparation method in preparing a medicament for treating or relieving diabetes.
In particular, the diabetes is type II diabetes.
The invention provides a pharmaceutical composition, which comprises the compound with PTP1B inhibitory activity or the compound with PTP1B inhibitory activity prepared by the preparation method, and pharmaceutically acceptable auxiliary materials.
The auxiliary materials are not particularly limited in the invention, and can be suitable auxiliary materials well known to those skilled in the art.
The above-mentioned compound having PTP1B inhibitory activity or the above-mentioned pharmaceutical composition may also be used in combination with other drugs for treating or alleviating diabetes.
Compared with the prior art, the invention provides two compounds with PTP1B inhibitory activity, which have the structure shown in formula 1 or formula 2. The invention discloses two hydroquinone-containing heteroterpene compounds discovered from ganoderma tropicalis for the first time. The compounds are found to have obvious PTP1B inhibitory activity through biological activity evaluation, enhance the sensitivity of insulin receptors and have application prospects in development of diabetes drugs.
Drawings
FIG. 1 is a schematic representation of Ganodulariporol F1HNMR spectrogram;
FIG. 2 is a schematic representation of Ganodulariporol F13CNMR spectrogram;
FIG. 3 is a DEPT spectrum of Ganodulariporol F;
FIG. 4 is an HSQC spectrum of Ganodulariporol F;
FIG. 5 is an HMBC spectrum of Ganodulariporol F;
FIG. 6 is of Ganodulariporol F1H-1H COSY spectrogram;
FIG. 7 is a ROESY spectrum of Ganodulariporol F;
FIG. 8 is a HRESIMS spectrum of Ganodulariporol F;
FIG. 9 is a schematic representation of ganoduroporol G1HNMR spectrogram;
FIG. 10 is a schematic representation of Ganodulariporol G13CNMR spectrogram;
FIG. 11 is a DEPT spectrum of Ganodulariporol G;
FIG. 12 is an HSQC spectrum of Ganodulariporol G;
FIG. 13 is an HMBC spectrum of Ganodulariporol G;
FIG. 14 is of Ganodulariporol G1H-1H COSY spectrogram;
FIG. 15 is a ROESY spectrum of Ganodulariporol G;
FIG. 16 is a HRESIMS spectrum of Ganodulariporol G.
Detailed Description
In order to further illustrate the present invention, the compounds having PTP1B inhibitory activity and uses thereof provided by the present invention are described in detail below with reference to examples.
Example 1
Isolation and purification of Ganodulariporol F and Ganodulariporol G
Drying fruiting body sample (5.0kg) of Ganoderma tropicalis, pulverizing into powder, extracting with 95% ethanol under heating and refluxing for 3 times, concentrating the extractive solution under reduced pressure, mixing to obtain ethanol extract, suspending the extract, sequentially extracting with petroleum ether, ethyl acetate and n-butanol for 3 times, and concentrating the extractive solution under reduced pressure to obtain petroleum ether, ethyl acetate and n-butanol fraction.
Ethyl acetate fractions (50.0g) of crude extracts of the pseudotropical ganoderma lucidum are separated by normal phase silica gel column chromatography, gradient elution is carried out in sequence by using a petroleum ether/ethyl acetate system (V: 10: 1, 8: 1, 6: 1, 4: 1, 2: 1, 1: 1, 1: 2), and collection is carried out in sections, each section is subjected to thin layer chromatography detection and then is combined, and 7 fractions Fr.1-Fr.7 are obtained.
Fr.6(5.0g) by reverse phase C18The column was subjected to gradient elution with methanol/water (V: 30:1 to 100:0) in this order, and the column was combined after detection on a thin-layer silica gel plate to obtain 5 fractions fr.6-1 to fr.6-5. Fr.6-4(65.0mg) was subjected to semipreparative HPLC [ V (acetonitrile): V (0.1% trifluoroacetic acid in water) 42:58 at a flow rate of 4 mL/min-1]Purification gave the compound Ganodulariporol F (3.2mg, t)R＝15min)。
Fr.7(6.0g) by reverse phase C18The column was subjected to gradient elution with methanol/water (V: V ═ 20:1 to 100:0) in this order, and the column was combined after detection on a thin-layer silica gel plate, whereby 6 fractions fr.7-1 to fr.7-6 were obtained. Fr.7-5(205.0mg) was takenSephadex column LH-20 chromatography, eluting with methanol to obtain 5 components Fr.7-5-1-Fr.7-5-5. Fr.7-5-4(45.0mg) was purified by semipreparative HPLC using [ V (methanol): V (0.1% aqueous trifluoroacetic acid): 72:28, flow rate 4 mL/min-1]Purification gave the compound Ganodulariporol G (3.0mg, t)R＝14.2min)。
Example 2
Structural characterization of ganoduroporol F and ganoduroporol G
The separated compounds Ganodulariporol F and Ganodulariporol G are respectively subjected to various modern spectral techniques such as nuclear magnetic resonance, infrared and mass spectrum detection, and the structures of the compounds are identified by combining a chemical method. The compounds ganoduroporol F and ganoduroporol G were identified as novel hydroquinone heterpenoids.
The structural formula of ganoduroporol F is as follows:
the structural formula of ganoduroporol G is as follows:
structural characterization of compounds ganoduroporol F and ganoduroporol G:
ganoduroporol F is a yellow oil, readily soluble in methanol. HRESIMS shows that the molecular formula of the compound is C30H32O9(calced for C30H32NaO9[M+Na]+559.1938, found 559.1939), the unsaturation is 15. Process for preparation of compound ganoduroporol F1The H-NMR spectrum (Table 1) gives 1,2, 4-trisubstituted benzenediol structural fragment deltaH 7.13(d,J＝2.9Hz,1H)，δH7.05(dd, J ═ 9.0,2.9Hz,1H) and δH6.89(d, J ═ 9.0Hz,1H), 1 p-hydroxybenzene ring structure segment deltaH7.44(d, J ═ 8.4Hz,2H) and δH6.80(d, J ═ 8.4Hz,2H), 2 trans-coupled olefin signals δH6.31(d, J ═ 15.9Hz,1H) and δH7.60(d, J ═ 15.9Hz,1H), 1 methyl signal δH1.65(s,3H),2 AlOxymethylene signals δH4.53(s,2H) and δH4.07(s, 2H). Comprehensive analysis thereof13C-NMR and DEPT spectra giving a total of 30 carbon signals including 1 methyl signal (CH)3) 5 methylene signals (CH)2) 14 methine signals (CH) and 10 quaternary carbon signals (C). The compound1H-NMR and13the C-NMR spectrum was very similar to that of ganoduroporol A in the reference (Liu, J.Q.; Lian, C.L.; Hu, T.Y.; Wang, C, F.; Xu, Y.; Xiao, L.; Liu, Z.Q.; Qiu, S.Q.; Cheng, B.H.two by way of farnesyl phenyl compounds with anti-inflammatory responses from ganoderima duropora.food chemistry.2018,04,97.), with the main difference being very similar to that of CH in the ganoduroporol A nuclear magnetic spectrum2The-2 'and CH-3' signals are measured by the one olefin quaternary carbon signal (. delta.) in the NMR spectrum of the compound Ganodulariporol FC) And one olefin methine group (. delta.)C/H) The signal substitution presumably occurs at the double bond between C-2 'and C-3' in the compound Ganodulariporol F. H-2' and H2Correlation of HMBC signal at-4 'with C-3' demonstrated that in the compound Ganodulariporol F. In the ROESY spectrum, H-2 'and H-4' are correlated, H-6 'and H-8' are correlated, and H-10 'and H-12' are correlated, demonstrating that2'，Δ6'And Δ10'The configuration of the double bond is Z, Z and E respectively. The coupling constants for H-2 "and H-3" were 15.9Hz, demonstrating a2”The configuration of the double bond is E.
Ganoduroporol G is a yellow oil, readily soluble in methanol. HRESIMS shows that the molecular formula of the compound is C30H34O10(calced for C30H34NaO10[M+Na]+577.2046, found 577.2044). The compound1H-NMR and13the C-NMR spectra (Table 1) are very similar to those of Ganodulariporol F, suggesting that they have the same structural backbone. The main difference is that compound ganoduroporol G has one more hydroxyl group (OH) at the C-6 "position, in addition to which a CH (6') -C (7') structural fragment is substituted at the CH (6') -C (7') double bond. The conclusion is speculated from H-5 and C-6, H-8 and C-6; and HMBC related signals of H-15 'and C-6', C-7 'and C-8' are determined. In the ROESY spectrum, H-2 'and H-4' are related, and H-10 'and H-12' are relatedProves a2'And Δ10'The configuration of the double bond is Z and E, respectively. The coupling constants for H-2 "and H-3" were 16.0Hz, demonstrating a2”The configuration of the double bond is E.
TABLE 1 of the Compounds Ganodulariporol F and Ganodulariporol G1H-NMR (500MHz) and13C-NMR (125MH) data with CD as solvent3OD
The physicochemical properties of the compounds ganoduroporol F and ganoduroporol G are as follows:
compound ganoduroporol F
Ganoduroporol F (1): yellow oil; UV-vis (MeOH) λmax[logε(L·mol-1·cm-1)]：307(4.4),224(4.0)nm；1H-NMR(CD3OD, 500MHz) and13C-NMR(CD3OD, 125MHz) data are shown in table 1; IR (KBr) vmax：3436,2925,2851,1630,1388,1168cm-1；HRESIMS calcd for C30H32NaO9[M+Na]+559.1939，found 559.1938。
Compound ganoduroporol G
Ganoduroporol G (2): yellow oil;
UV-vis(MeOH)λmax[logε(L·mol-1·cm-1)]：328(4.1),288(3.8)nm；1H-NMR(CD3OD, 500MHz) and13C-NMR(CD3OD, 125MHz) data are shown in table 1; IR (KBr) vmax：3414,2927,2859,1610,1474,1263,1195cm-1；HRESIMS calcd for C30H34NaO10[M+Na]+577.2046，found 577.2044。
Example 3
PTP1B inhibitory Activity assays for Compounds Ganodulariporol F and Ganodulariporol G
This example describes the measurement of the inhibitory activity of PTP1B using the compounds Ganodulariporol F and Ganodulariporol G of example 1, as determined by the method reference (Li-Man Zhou, Fan-Dong Kong, Peng Fan, Qing-Yun Ma, Qing-Yi Xie, Jiu-Hui Li, Hai-Zhou Zhung, Zhi-Hui Zheng, Jing-Zhen Yuan, Hao-Fu Dai, Du-Qing Luo, You-Xing Zhuao, Indo-dependent optics with Protein type photoshase enzyme inhibition activity, from the said one-Derived fungi filtration bacterium KF, D28.journal of Natural Products, Ganodulario G2019, 82: Garoriporol G, as well as the measurement of the gradient of the activity of the sample prepared by diluting the sample with different concentrations of the compound F, G, DMSO G, and gradient L2620. mu. for the measurement.2O,3 mu L of pNPP substrate solution), judging the inhibitory activity of the compound to be detected through the reaction result of nonlinear fitting, and calculating IC (integrated Circuit)50The value is obtained. A positive control; sodium orthovanadate, the reaction temperature was 37 ℃ and the light absorption at a wavelength of 405nm was measured.
The results are shown in table 2, and the compound ganoduroporol F shown in the formula 1 and the compound ganoduroporol G shown in the formula 2 both have good inhibitory activity on PTP1B, and have application prospects in development of drugs for treating type II diabetes.
TABLE 2 inhibitory Activity of the Compounds on PTP1B IC50(μM)
The above description of the embodiments is only intended to facilitate the understanding of the method of the invention and its core idea. It should be noted that, for those skilled in the art, it is possible to make various improvements and modifications to the present invention without departing from the principle of the present invention, and those improvements and modifications also fall within the scope of the claims of the present invention.
Claims (4)
1. A compound having PTP1B inhibitory activity, having the structure represented by formula 1 or formula 2:
2. a process for the preparation of a compound according to claim 1, comprising the steps of:
A) extracting the dried fruiting body powder of the Ganoderma tropicalis with ethanol under heating and refluxing to obtain ethanol extractive solution;
B) concentrating the ethanol extract under reduced pressure, adding water for suspension, extracting with ethyl acetate, and distilling and concentrating the extract to obtain ethyl acetate extract;
C) separating the ethyl acetate extract by normal phase silica gel column chromatography to obtain components Fr.1-Fr.7;
d-1) taking Fr.6, inverting C18Performing column chromatography to obtain Fr.6-1-Fr.6-5;
e-1) taking Fr.6-4, and purifying by using semi-preparative high performance liquid chromatography to obtain a compound shown in a formula 1;
d-2) taking Fr.7 and inverting C18Performing column chromatography to obtain Fr.7-1-Fr.7-6;
e-2) taking Fr.7-5, carrying out chromatography by a sephadex column LH-20, and eluting by methanol to obtain Fr.7-5-1-Fr.7-5-5;
f-2) taking Fr.7-5-4, and purifying by using semi-preparative high performance liquid chromatography to obtain a compound shown in the formula 2;
in the step C), an eluent for normal phase silica gel column chromatographic separation is petroleum ether/ethyl acetate, and the volume ratio of the petroleum ether to the ethyl acetate is 10: 1-1: 2;
in said step D-1), the phase inversion C18An eluent for column chromatography is methanol/water, and the volume ratio of the methanol to the water is 30: 1-100: 0;
in the step E-1), the mobile phase of the semi-preparative high performance liquid chromatography is a mixed solvent of acetonitrile and trifluoroacetic acid;
in the step D-2), the phase inversion C18An eluent for column chromatography is methanol/water, and the volume ratio of the methanol to the water is 20: 1-100: 0；
In the step F-2), the mobile phase of the semi-preparative high performance liquid chromatography is a mixed solvent of methanol and trifluoroacetic acid.
3. Use of a compound according to claim 1 having PTP1B inhibitory activity in the manufacture of a medicament for the treatment or alleviation of diabetes.
4. A pharmaceutical composition comprising a compound of claim 1 having PTP1B inhibitory activity and a pharmaceutically acceptable adjuvant.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010273869.9A CN111302942B (en) | 2020-04-09 | 2020-04-09 | Compound with PTP1B inhibitory activity and application thereof |
| PCT/CN2021/083890 WO2021204018A1 (en) | 2020-04-09 | 2021-03-30 | Compounds possessing ptp1b inhibitory activity, and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010273869.9A CN111302942B (en) | 2020-04-09 | 2020-04-09 | Compound with PTP1B inhibitory activity and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN111302942A CN111302942A (en) | 2020-06-19 |
| CN111302942B true CN111302942B (en) | 2022-03-01 |
Family
ID=71153950
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202010273869.9A Active CN111302942B (en) | 2020-04-09 | 2020-04-09 | Compound with PTP1B inhibitory activity and application thereof |
Country Status (2)
| Country | Link |
|---|---|
| CN (1) | CN111302942B (en) |
| WO (1) | WO2021204018A1 (en) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111302942B (en) * | 2020-04-09 | 2022-03-01 | 中国热带农业科学院热带生物技术研究所 | Compound with PTP1B inhibitory activity and application thereof |
| CN114605370B (en) * | 2022-03-25 | 2024-01-05 | 中国科学院西北高原生物研究所 | Chebula acid cracking compound in chebula fruit, and preparation method and application thereof |
| CN115010598B (en) * | 2022-04-11 | 2023-06-23 | 中国科学院昆明植物研究所 | Compound Villanovane VI, pharmaceutical composition thereof, preparation method and application thereof |
| CN114716406B (en) * | 2022-04-15 | 2023-04-25 | 山东省农业科学院 | Semen Scaphii Lychnophori extract with xanthine oxidase activity inhibiting effect, and its preparation method and application |
| CN115011640B (en) * | 2022-06-17 | 2024-08-16 | 自然资源部第三海洋研究所 | Application and method for preparing compound by utilizing monascus durian A2 |
Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104557658A (en) * | 2014-11-03 | 2015-04-29 | 南昌大学 | Haematinic acid esterified chain diterpenoid compound as well as preparation and application thereof |
| CN104873520A (en) * | 2014-02-27 | 2015-09-02 | 天津药物研究院 | 11 beta-hydroxysteroid dehydrogenase inhibitor and its pharmaceutical composition and use |
| CN105175252A (en) * | 2015-10-22 | 2015-12-23 | 云南民族大学 | Diterpenoid compounds, and preparation method and application thereof |
| CN106220701A (en) * | 2016-06-29 | 2016-12-14 | 浙江工业大学 | triterpene compound and preparation method and application thereof |
| CN106748666A (en) * | 2016-12-01 | 2017-05-31 | 南昌大学 | A kind of hypoglycemic natural drug and its preparation diabetes or obesity drug purposes |
| CN106916133A (en) * | 2017-01-18 | 2017-07-04 | 东北大学 | A kind of phloroglucin derivative with suppression PTP1B activity and preparation method thereof, application |
| CN107056867A (en) * | 2017-04-27 | 2017-08-18 | 峨眉山国芝堂生物科技有限公司 | Ganodenic acid compound, its Pharmaceutical composition and its application |
| CN107163009A (en) * | 2017-04-27 | 2017-09-15 | 峨眉山国芝堂生物科技有限公司 | The miscellaneous terpene compound of ganoderma lucidum, its Pharmaceutical composition and its application |
| CN108892651A (en) * | 2018-08-01 | 2018-11-27 | 中国科学院昆明植物研究所 | A kind of mixed source terpene dimer class compound and its pharmaceutical composition and its application |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20140114736A (en) * | 2010-10-19 | 2014-09-29 | 엘셀릭스 테라퓨틱스 인코포레이티드 | Chemosensory receptor ligand-based therapies |
| US11510890B2 (en) * | 2017-09-15 | 2022-11-29 | Societe Des Produits Nestle S.A. | Meroterpenoid compounds for use in the prevention and treatment of a neurological disorder |
| CN111302942B (en) * | 2020-04-09 | 2022-03-01 | 中国热带农业科学院热带生物技术研究所 | Compound with PTP1B inhibitory activity and application thereof |
-
2020
- 2020-04-09 CN CN202010273869.9A patent/CN111302942B/en active Active
-
2021
- 2021-03-30 WO PCT/CN2021/083890 patent/WO2021204018A1/en active Application Filing
Patent Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104873520A (en) * | 2014-02-27 | 2015-09-02 | 天津药物研究院 | 11 beta-hydroxysteroid dehydrogenase inhibitor and its pharmaceutical composition and use |
| CN104557658A (en) * | 2014-11-03 | 2015-04-29 | 南昌大学 | Haematinic acid esterified chain diterpenoid compound as well as preparation and application thereof |
| CN105175252A (en) * | 2015-10-22 | 2015-12-23 | 云南民族大学 | Diterpenoid compounds, and preparation method and application thereof |
| CN106220701A (en) * | 2016-06-29 | 2016-12-14 | 浙江工业大学 | triterpene compound and preparation method and application thereof |
| CN106748666A (en) * | 2016-12-01 | 2017-05-31 | 南昌大学 | A kind of hypoglycemic natural drug and its preparation diabetes or obesity drug purposes |
| CN106916133A (en) * | 2017-01-18 | 2017-07-04 | 东北大学 | A kind of phloroglucin derivative with suppression PTP1B activity and preparation method thereof, application |
| CN107056867A (en) * | 2017-04-27 | 2017-08-18 | 峨眉山国芝堂生物科技有限公司 | Ganodenic acid compound, its Pharmaceutical composition and its application |
| CN107163009A (en) * | 2017-04-27 | 2017-09-15 | 峨眉山国芝堂生物科技有限公司 | The miscellaneous terpene compound of ganoderma lucidum, its Pharmaceutical composition and its application |
| CN108892651A (en) * | 2018-08-01 | 2018-11-27 | 中国科学院昆明植物研究所 | A kind of mixed source terpene dimer class compound and its pharmaceutical composition and its application |
Non-Patent Citations (1)
| Title |
|---|
| 灵芝活性组分在小鼠体内的降糖功效研究;包焜等;《中国兽药杂志》;20151231;第49卷(第1期);第29-32页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2021204018A1 (en) | 2021-10-14 |
| CN111302942A (en) | 2020-06-19 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN111302942B (en) | Compound with PTP1B inhibitory activity and application thereof | |
| CN109912680B (en) | Oleane-type triterpenoid saponin and extraction separation method and application thereof | |
| CN110330503B (en) | Compound, preparation method and application thereof, and anti-rheumatoid arthritis drug | |
| Li et al. | A norsesquiterpene lactone and a benzoic acid derivative from the leaves of Cyclocarya paliurus and their glucosidase and glycogen phosphorylase inhibiting activities | |
| CN109942649B (en) | Indole glycoside compound and extraction and separation method and application thereof | |
| KR101080648B1 (en) | A method for isolating and producing highly-concentrated Eupatilin and Jaceosidine from the extract of Artemisia species by using Centrifugal Partition Chromatography | |
| CN109320571A (en) | The method for extracting luteolin kind compound and cynaropicrin | |
| CN106674309B (en) | Tonka bean camphor glycosides compounds and its preparation method and application | |
| CN111018877B (en) | Sesquiterpene derivative in elecampane inula root, preparation method and application thereof | |
| CN115991692B (en) | Preparation method and application of spirodienone lignan compound in Isatis tinctoria | |
| CN112608306B (en) | Preparation method and application of flavonoid saponin new ketone A in spina gleditsiae | |
| CN111647031B (en) | Alkaloid and extraction and separation method and application thereof | |
| CN111233807B (en) | Preparation method and quality control method of high-purity kaempferol-7, 4' -dimethyl ether | |
| CN106674299B (en) | Carbene glycosides compound and its preparation method and application | |
| CN114539192B (en) | Rosin alkane type diterpenoid compound and preparation method and application thereof | |
| Luo et al. | Two new β-carboline-type alkaloids from Stellaria dichotoma var. lanceolata | |
| CN103113439A (en) | Method for preparing kaempferol-3-O-Beta-D-glucuronide in euphorbia sororia | |
| CN105924351A (en) | Pharmaceutical composition of diprophylline and medical application thereof | |
| CN1935798A (en) | Method for preparing and rographalide | |
| WO2021204192A1 (en) | Use of compound as sirt1 receptor agonist | |
| CN106749147B (en) | Hypoglycemics and preparation method thereof, purposes | |
| JPH0819039B2 (en) | New bioactive substance derived from propolis | |
| CN102050852B (en) | 2'-O-rhamnosyl swertisin, preparation of analogues thereof, and application thereof | |
| CN116003371B (en) | Terpenoid, and extraction method and application thereof | |
| CN111675717B (en) | Tetrandra monomer compound and its extraction method and use |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |