CN115124531A - 4-azatryptanthrin aromatic thioether derivatives, and preparation method and application thereof - Google Patents
4-azatryptanthrin aromatic thioether derivatives, and preparation method and application thereof Download PDFInfo
- Publication number
- CN115124531A CN115124531A CN202210948891.8A CN202210948891A CN115124531A CN 115124531 A CN115124531 A CN 115124531A CN 202210948891 A CN202210948891 A CN 202210948891A CN 115124531 A CN115124531 A CN 115124531A
- Authority
- CN
- China
- Prior art keywords
- human
- azatryptanthrin
- substituted
- cell
- aromatic thioether
- 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.)
- Pending
Links
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains three hetero rings
- C07D471/14—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
Abstract
The invention discloses 4-azatryptanthrin aromatic thioether derivatives, and application of the compounds as antitumor activities, wherein the general formulas of the derivatives are shown as (I) and (II). The compound shown in the general formula has better inhibition effect on tumor cell human lung cancer cell line A549, human chronic myelogenous leukemia cell K562, human prostate cancer cell PC3, human hepatoma cell Hep-G2 and the like, especially has outstanding inhibition activity on human leukemia cell line K562, can be used for developing candidate drugs with novel structure and higher antitumor activity by taking natural product alkaloid tryptanthrin as a lead compound,
Description
Technical Field
The invention relates to the technical field of medicinal chemistry, in particular to a preparation method and application of 4-azatryptanthrin aromatic thioether derivatives.
Background
Cancer is a pathological proliferation of a group of abnormal cells, rapid, uncontrolled, and second leading cause of death worldwide to cardiovascular disease. Indoleamine 2,3-dioxygenase (IDO) is becoming an important new therapeutic target for treating cancers, nervous system diseases and other diseases characterized by pathological tryptophan metabolism, has a new drug target and a new mechanism, can be applied to treating a plurality of major diseases such as tumors, Alzheimer diseases, depression, cataract and the like, and has wide social and economic benefit prospects. However, only a few structural classes of compounds are known IDO inhibitors.
Tryptanthrin (Tryptanthrin) is an indoline alkaloid with a chemical name of indole [2,1-b ] quinazoline-6, 12-dione, and exists in blueproducing plants, such as India tinctoria, isatis tinctoria, Polygonum tinctorium (strobilanthes) Kuntze and the like, and is found in natural indigo, isatis roots, microbial fermentation liquor and marine microorganisms which are finished traditional Chinese medicines. Tryptanthrin has wide biological activity, and mainly has the activities in the aspects of resisting tumors, inflammation, bacteria, coronavirus (NL63), plant virus (TMV) and the like. The tryptanthrin derivative research progresses as follows:
in 2013, Yang et al [ Yang S.S., LiX.S., Hu F.F., Li Y.L., Yang Y.Y., Yan J.K., Kuang C.X., Yang Q.discovery of Tryputanin Derivatives as force inhibitory substances Indolamine 2,3-Dioxygenase with Therapeutic activity in Leaves Lung Cancer (LLC) Tumor-Bearing Mice [ J ] J.Med.chem.2013,56, 8321-containing 8331] were synthesized by design and screened for structural effect analysis, and found that the natural compound tryptamine ketone is a novel Indoleamine Dioxygenase 1(IDO1) inhibitor. Wherein the 8F tryptanthrin compound shows better inhibitory activity on the nanomolar level, and the 8F tryptanthrin obviously enhances the proliferation of T cells in vitro. When administered to Lewis Lung Carcinoma (LLC) tumor-bearing mice, 8F tryptanthrin significantly inhibited IDO-1 activity and inhibited tumor growth, 8F tryptanthrin also reduced the number of Foxp3+ regulatory T cells (Tregs), which are thought to prevent the development of an effective anti-tumor immune response.
In 2015, Jun et al [ JunK-Y, Parks-E, liangJ-L, Jahng Y, Kwon Y. Benzo [ b ] typtanthrin inhibitors MDR1, Topoisimeraseactivity, and revertes Adriamycin Resistance in Breast cancer cells. chem. Med. chem2015,10,827 835] found that the benzotriazol derivative could induce apoptosis of HCT15 colon cancer cells by cleavage of caspase-3 and PARP, and that doxorubicin Resistance could be reversed by down-regulating multidrug Resistance protein 1(MDR1) of doxorubicin-resistant MCF7 breast cancer cells (MCF7 adr). Therefore, derivatives of the benzotriazolones can improve MDR reversal.
In 2015, Kamal [ kamala., reddyb.v.s., srideevib., Ravikumar a., venkatswarru a., Sravanthi g., sridesevi j.p., Yogeeswari p., Sriram d.synthesis and biological evaluation of phaitheron anti-mycobacteriological agents.bioorg.med.chem.lett.2015,25, 3867-3872 ] tryptamine ketone and its analogs were found to exhibit strong anti-tubercular activity against multidrug resistant tuberculosis, MICs being (0.5-1) lg/mL. Molecular docking studies have shown that InhA has proven to be an effective antimicrobial target, and tryptanthrin derivatives have high affinity with the mycobacterium tuberculosis drug target InhA.
In 2020, researches on azatryptanthrin and derivatives thereof on Leishmania have shown that azatryptanthrin and derivatives thereof have obvious inhibitory activity, especially when 4 azatryptanthrin C8 is substituted by halogen or an electron-withdrawing group, the anti-trypanosome activity of 8-nitro-4-azatryptanthrin is 100 times that of the parent compound tryptanthrin, and the research value is better.
Disclosure of Invention
One of the purposes of the invention is to provide a 4-azatryptanthrin aromatic thioether derivative.
The invention also aims to provide a compound and a composition containing the compound or the isomer thereof, the salt thereof, the solvent thereof.
It is also an object of the present invention to provide the use of the above-mentioned compounds or said compositions.
It is also an object of the present invention to provide a method for the antitumor activity of the above compound or the composition.
It is a further object of the present invention to provide the use of a derivative of any of the above compounds or compositions in the manufacture of a medicament as an inhibitor of indoleamine-2, 3-dioxygenase 1(IDO1) and/or tryptophan-2, 3-dioxygenase (TDO).
In order to realize the purpose, the invention adopts the following technical scheme:
a4-azatryptanthrin aromatic thioether derivative has a structure shown in general formulas (I) and (II):
wherein the content of the first and second substances,
R 1 selected from the group consisting of optionally substituted or unsubstituted aryl structures, optionally substituted or unsubstituted aromatic heterocyclic structures.
R 2 Is independently selected from hydrogen, nitro, C1-C4 alkoxy, C1-C4 alkylHalogen, trifluoromethyl, trifluoromethoxy, amino, hydroxyl, cyano, carboxyl, methylsulfonyl, sulfonic acid.
R 1 Is substituted or unsubstituted phenyl, or substituted or unsubstituted pyridine or pyrimidine. The substituent of the substituted phenyl is halogen; the substituent of the substituted pyridine or pyrimidine is trifluoromethyl.
The 4-azatryptanthrin aromatic thioether derivatives are selected from the following compounds:
the invention also provides a preparation method of the 4-azatryptanthrin aromatic thioether derivative, which comprises the following steps:
the invention also provides a composition which contains the compound or the isomer thereof, the salt thereof or the solvent compound thereof, and an auxiliary agent or an anti-tumor medicinal preparation which can be used for treating tumors; preferably, the composition is selected from granules, pills, tablets, oral liquids, injections, powders and the like.
The compound or the isomer, the salt, the solvate or the composition thereof is used for preparing the antitumor drug, preferably, the Human tumor cells comprise a Human lung cancer cell line A549(Human non cancer cell lung cell), a Human chronic myeloid leukemia cell K562(Human leukemia cell line), a Human prostate cancer cell PC3(Human cancer of prostate cell line) and a Human hepatoma cell Hep-G2(Human hepatoma cell line); more preferably, the tumor is leukemia, lung cancer, liver cancer and prostate cancer.
The invention also provides a method for preparing the anti-tumor medicine. Allowing said compound or stereoisomer thereof, or salt or solvate thereof, or said composition to act on tumor cells or their living environment; preferably, the tumor cells are leukemia cells, liver cancer cells, lung cancer cells and prostate cancer cells
The present invention also provides a process for preparing an anti-tumor drug comprising the process step of contacting said compound or a stereoisomer thereof, or a salt or solvate thereof, or said composition.
The invention also provides the application of the derivative in preparing a medicament serving as an indoleamine-2, 3-dioxygenase 1(IDO1) and/or tryptophan-2, 3-dioxygenase (TDO) inhibitor.
The term "substituted" as used herein refers to any one or more hydrogen atoms on the designated atom or group.
The term "aryl" refers to a monocyclic or bicyclic aromatic hydrocarbon group having 6 to 12 carbon atoms in the ring portion, such as phenyl, all of which may be substituted.
The term "halogen" or "halogen atom" refers to fluorine, chlorine, bromine and iodine.
The term "arylheterocyclyl" refers to substituted and unsubstituted aromatic 5 or 6 membered monocyclic groups, 9-or 10-membered bicyclic groups, and 11 to 14 membered tricyclic groups having at least one heteroatom (O, S or N) in at least one ring, preferably 1, 2 or 3 heteroatoms selected from O, S and N.
The compounds of the invention are understood to include both the free form and salts thereof, unless otherwise indicated. The term "salt" means an acid and/or base salt formed from an inorganic and/or organic acid and a base.
By adopting the technical scheme, the invention takes substituted aniline as a starting raw material to synthesize a series of various substituted isatin derivative intermediates; reacting halogen-substituted anthranilic acid with triphosgene to prepare a substituted isatoic anhydride derivative; synthesizing tryptanthrin derivatives from substituted isatin and substituted isatoic anhydride through an optimized Bergman condensation reaction; and finally, heating and stirring the mixture under the action of NMP solvent by taking potassium carbonate as a catalyst to obtain the 4-azatryptanthrin aromatic thioether derivative. The compounds are found to have better inhibition effect on tumor cells, have better biological activity on anti-tumor cells (such as human chronic myelogenous leukemia cells (K562), human non-small cell lung cancer cells (A549), human hepatoma cells (Hep-G2) and human prostate cancer cells (PC 3)), and provide scientific basis and research direction for research and development of novel anti-tumor drugs.
Drawings
FIG. 1 shows the expression of IDO1 protein after treatment of K562 cells with Compound 1, and GAPDH is a reference protein.
Examples
The invention is further illustrated by the following examples. It should be understood that the method described in the examples is only for illustrating the present invention and not for limiting the present invention, and that simple modifications of the preparation method of the present invention based on the concept of the present invention are within the scope of the present invention. All the starting materials and solvents used in the examples are commercially available products.
Example 1
(1) Preparation of substituted isatins
Adding 220mL of distilled water into a 500mL round-bottom three-neck flask in advance, heating to 50 ℃, adding anhydrous sodium sulfate (0.1mol), stirring until the anhydrous sodium sulfate is completely dissolved, completely dissolving a corresponding aniline solution (0.1mol) by using 5% dilute hydrochloric acid, dropwise adding the aniline solution into a reaction system, continuously dropwise adding a hydroxylamine hydrochloride aqueous solution (0.3mol), refluxing for 5-8h, monitoring by TLC, cooling after the reaction is complete, carrying out vacuum filtration, and drying to obtain a reaction type intermediate compound 3.
Adding the intermediate compound 3(0.1mol) into 90% concentrated sulfuric acid in batches in a 250mL round-bottom three-neck flask, heating and stirring at 90 ℃ for 3-5h, cooling to room temperature, adding into 500mL of ice-water mixture under rapid stirring, closing a ring for 30min, performing suction filtration, washing with water, performing vacuum suction filtration, and drying to obtain various substituted isatin derivatives.
(2) Preparation of halogen-substituted tryptanthrin
In a 50mL round-bottom three-necked flask, the substituted isatin (0.1mol) prepared above and 1, 8-diazabicyclo [5.4.0] undec-7-ene (DBU) (0.3mol) were dissolved in DMF solvent. In another 50mL round bottom three-neck flask, anthranilic acid (0.1mol), N-methylmorpholine (NMM) (0.2mol) and O-benzotriazole-tetramethyluronium Hexafluorophosphate (HBTU) (0.1mol) are dissolved in DMF solvent, after complete dissolution, prepared isatin and DBU solution are dropwise added, stirred at room temperature for 24h-48h, monitored by TLC, after complete reaction, pure water is added to quench the reaction, dichloromethane is extracted, and column chromatography is performed (dichloromethane/methanol-40/1) to obtain orange yellow solid with yield of 30-60%.
Stirring at room temperature for 30min
(3) Preparation of target compound 4-azatryptanthrin aromatic thioether derivative
Adding a substituted tryptanthrin compound (0.01mol) into a 50mL round-bottom three-neck flask, adding a reaction solvent N-methylpyrrolidone (10mL), taking potassium carbonate (0.03mol) as a catalyst, heating and stirring at 70 ℃ for 5-8h, cooling to room temperature, adding pure water to quench the reaction, standing for 30min, carrying out vacuum filtration, drying, and carrying out column chromatography separation to obtain a light yellow solid with the yield of 35-50%.
Other target compounds, namely 4-azatryptanthrin aromatic thioether derivatives, adopt corresponding raw materials or substituents according to the synthetic method of the step (4) in the example.
The structure, nuclear magnetic resonance hydrogen spectrum and high resolution mass spectrum data of the synthesized partial 4-azatryptanthrin aromatic thioether derivative are shown in table 1, and the physicochemical properties are shown in table 2.
Table 1 shows nmr hydrogen spectra, carbon spectra and high resolution mass spectra data of some compounds.
TABLE 14 Aza tryptanthrin aromatic thioether derivatives 1 HNMR and ESI-HRMS data
Table 2 physicochemical properties of the target compounds
TABLE 24 physicochemical Properties of Aza tryptanthrin aromatic thioether derivatives
Pharmacological example 1:
and (4) testing the antitumor activity.
The inhibitory activity of the compounds on A549(human non-small cell lung cancer cells), PC-3 (human prostate cancer cells), HepG 2(human liver cancer cells) and K562(human chronic myelogenous leukemia cells) was determined by the MTT method.
And (4) inoculating cells (suitable for adherent cells and suspension cells).
1. Selecting cells: selecting cells in logarithmic growth phase according to a cell growth curve;
2. digesting the cells: digesting the monolayer cultured cells by using 0.25% trypsin, and preparing a single cell suspension by using a DMEM/1640 culture solution containing 10% FBS;
3. cell counting: soaking the cell counting plate and the blood cover plate in absolute ethyl alcohol; taking 10 mu L of cell suspension, and dripping the cell suspension on the edge of the blood cover plate to ensure that the suspension is filled between the blood cover plate and the counting plate and the blood cover plate can not overflow or overflow into the glass grooves at two sides; the number of cells in the square grid of the counting plate was observed under a microscope. Calculating according to the formula: (sum of 4 large cells/4). times.10 4 X volume of cell sap 3X 10 4 X Total cell mixture required (typical density 3X 10) 4 Other density calculation can be changed according to different cell properties);
4. color development, measured (applicable to adherent cells). Adding 20 mu L of MTT solution (5mg/mL, 10% MTT), incubating for 4h, and terminating the culture; sucking out the solution in the culture plate by adopting a liquid suction mode; adding 150 mu LDMSO into each hole to dissolve formazan particles, shaking the shaking table for 10min (150rpm/min), mixing uniformly, and measuring OD values at 490 and 570nm by using an enzyme-labeling instrument.
The inhibition rate is 1- (the OD value of the drug addition group-the OD value of the blank group)/(the OD value of the negative group-the OD value of the blank group) × 100%;
blank control wells: 200 mul of culture medium +150 mul of LDMSO;
negative control wells: 180 μ L of cell suspension +20 μ L LDMSO +20 μ L LMTT +150 μ L LDMSO;
adding a medicine hole: 180 μ L of cell suspension +20 μ L +20 μ LMTT +150 μ LDMSO of drug at different concentrations;
the examples of the present invention are given to illustrate the technical solution of the present invention, but the contents of the examples are not limited thereto, and the experimental results of the target compounds at a concentration of 10. mu.M are shown in Table 3.
TABLE 3 inhibitory Activity of the target Compound 4-azatryptanthrin aromatic thioether derivatives against four tumor cells
TABLE 34 inhibitory Activity of Aza tryptanthrin aromatic thioether derivatives against four tumor cells at a concentration of 10. mu.M
The test results are the average of three determinations.
The cytotoxicity of the compound on human non-small cell lung cancer cells A549, human prostate cancer cells PC-3, human liver cancer cells HepG2 and chronic myelogenous leukemia cells K562 is evaluated by adopting an MTT method. The primary screening activity shows that the compound 1 and the compound 2 show better inhibitory activity to A549, K562 and Hep-G2 cell lines, and have equivalent activity to a positive control on a PC3 cell line. All the compounds show better cytotoxicity on A549 cells.
The experimental activity data show that the tested 4-azatryptanthrin aromatic thioether derivatives have good inhibitory activity on the anti-tumor, the primary screening inhibition rate of partial compounds at the tested concentration is superior to that of commercial compounds imatinib and 5-fluorouracil positive control, and the compounds can be used as potential candidate lead compounds for anti-tumor and have good research and application values.
Pharmacological example 2: IDO1 immunoblot experiments.
Chronic myelogenous leukemia K562 cells (5X 10) 5 ) The cells were plated in 6-well plates and after 24h cell stabilization, treated with different concentrations of compound 7AS1 for 48 h.
Cells were collected and lysed in radioimmunoprecipitation assay (RIPA) buffer. Protein concentration was measured using BCA protein assay reagent (Solarbio, beijing, china) and 30mg aliquots of protein samples were separated on 12.5% sodium dodecyl sulfate-polyacrylamide gels and transferred to (polyvinylidene fluoride (PVDF) membranes).
The membrane was blocked in TBST buffer containing 5% skim milk for 2h and incubated with the cognate antibody overnight at 4 ℃.
TBST washing was performed twice and incubated with appropriate secondary antibodies for 1 hour, TBST washing, enhanced chemiluminescence visualization of the resulting protein bands. The results are shown in FIG. 1.
The results show that after compound 1 treatment, IDO1 showed a clear downward trend and was concentration dependent. Therefore, IDO1 is likely to be a target of action of 4-azatryptanthrin aromatic thioether derivatives, and is worthy of intensive research.
Claims (10)
1. A4-azatryptanthrin aromatic thioether derivative is characterized in that the compound has a structure shown in a general formula (I) or (II):
wherein R is 1 Is an optionally substituted or unsubstituted aryl structure, or an optionally substituted or unsubstituted aromatic heterocyclic structure; r is 2 Is hydrogen, nitryl, C1-C4 alkoxy, C1-C4 alkyl, halogen, trifluoromethyl, trifluoromethoxy, amino, hydroxyl, cyano, carboxyl, methylsulfonyl or sulfonic group.
2. A class of 4-azatryptanthrin aromatic thioether derivatives according to claim 1, wherein: r 1 Is substituted or unsubstituted phenyl, or substituted or unsubstituted pyridine or pyrimidine.
3. A class of 4-azatryptanthrin aromatic thioether derivatives according to claim 2, wherein: the substituent of the substituted phenyl is halogen; the substituent of the substituted pyridine or pyrimidine is trifluoromethyl.
4. The 4-azatryptanthrin aromatic thioether derivative according to claim 1, comprising a stereoisomer or a salt thereof or a solvate thereof, wherein: r is 1 Is a substituted or unsubstituted phenyl, or, a substituted or unsubstituted pyridine or pyrimidine; r 2 Is hydrogen, nitryl, C1-C4 alkoxy, C1-C4 alkyl, halogen, trifluoromethyl, trifluoromethoxy, amino, hydroxyl, cyano, carboxyl, methylsulfonyl or sulfonic group.
5. A process for the preparation of 4-azatryptanthrin aromatic thioether derivatives according to any of claims 1 to 4, wherein: the method comprises the following steps:
6. a composition characterized by: comprising the compound of any one of claims 1 to 4, a stereoisomer thereof, a salt thereof, or a solvate thereof, and a pharmaceutical adjuvant or an antitumor agent.
7. Use of a composition of a compound according to any one of claims 1 to 4 or a stereoisomer or a salt or solvate thereof in the preparation of an anti-tumor medicament.
8. Use of a combination of compounds according to any one of claims 1 to 4 or stereoisomers or salts or solvates thereof for the manufacture of a medicament for use as an indoleamine-2, 3-dioxygenase 1(IDO1) and/or tryptophan-2, 3-dioxygenase (TDO) inhibitor.
9. The composition of claim 7, wherein: the tumor is a human tumor cell line.
10. The composition of claim 9, wherein: the Human tumor cells comprise a Human lung cancer cell line A549(Human nonnuclear cell lung cancer cell), a Human chronic myelogenous leukemia cell K562(Human leukamia cell line), a Human prostate cancer cell PC3(Human cancer of prostate cell line) and a Human hepatoma cell Hep-G2(Human hepatoma cell line).
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210948891.8A CN115124531A (en) | 2022-08-09 | 2022-08-09 | 4-azatryptanthrin aromatic thioether derivatives, and preparation method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210948891.8A CN115124531A (en) | 2022-08-09 | 2022-08-09 | 4-azatryptanthrin aromatic thioether derivatives, and preparation method and application thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN115124531A true CN115124531A (en) | 2022-09-30 |
Family
ID=83385622
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202210948891.8A Pending CN115124531A (en) | 2022-08-09 | 2022-08-09 | 4-azatryptanthrin aromatic thioether derivatives, and preparation method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN115124531A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115710276A (en) * | 2022-11-21 | 2023-02-24 | 贵州大学 | 7-fatty amine substituted tryptanthrin derivative, preparation method and application thereof |
Citations (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1995013807A1 (en) * | 1993-11-19 | 1995-05-26 | Pathogenesis Corporation | INDOLO[2,1-b]QUINAZOLINE-6,12-DIONE ANTIBACTERIAL COMPOUNDS AND METHODS OF USE THEREOF |
| WO2000018769A2 (en) * | 1998-09-30 | 2000-04-06 | Wrair (Walter Reid Army Institute Of Research) | INDOLO[2,1-b]QUINAZOLE-6,12-DIONE ANTIMALARIAL COMPOUNDS AND METHODS OF TREATING MALARIA THEREWITH |
| WO2004064759A2 (en) * | 2003-01-21 | 2004-08-05 | Chiron Corporation | Use of tryptanthrin compounds for immune potentiation |
| CN103054870A (en) * | 2013-01-08 | 2013-04-24 | 复旦大学 | Use of tryptanthrin compound as indoleamine 2,3-dioxygenase (IDO) inhibitor |
| CN105153148A (en) * | 2015-06-18 | 2015-12-16 | 玉林师范学院 | Tryptanthrin alkaloid salt, and preparation method and application thereof |
| CN105330666A (en) * | 2015-11-27 | 2016-02-17 | 西北大学 | Novel tryptanthrin derivative, synthetic method and medicinal application thereof |
| CN107260743A (en) * | 2016-04-05 | 2017-10-20 | 北京大学 | Azatryptamine ketone derivatives as IDO1 and/or TDO inhibitor purposes |
| CN108969522A (en) * | 2017-06-05 | 2018-12-11 | 复旦大学 | Purposes of the N- benzyl tryptamines ketones derivant as tryptophan dioxygenase (TDO) inhibitor |
| CN109956942A (en) * | 2017-12-25 | 2019-07-02 | 上海翔锦生物科技有限公司 | Tryptamines ketones derivant and application thereof |
| CN110143964A (en) * | 2019-06-17 | 2019-08-20 | 西北大学 | Tryptamines ketone derivatives and its pharmaceutical usage |
| CN114805353A (en) * | 2022-01-11 | 2022-07-29 | 贵州大学 | Synthesis of azatryptanthrin derivative and application of azatryptanthrin derivative in prevention and treatment of plant pathogenic bacteria, fungi bactericide and anti-plant virus preparation |
-
2022
- 2022-08-09 CN CN202210948891.8A patent/CN115124531A/en active Pending
Patent Citations (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1995013807A1 (en) * | 1993-11-19 | 1995-05-26 | Pathogenesis Corporation | INDOLO[2,1-b]QUINAZOLINE-6,12-DIONE ANTIBACTERIAL COMPOUNDS AND METHODS OF USE THEREOF |
| WO2000018769A2 (en) * | 1998-09-30 | 2000-04-06 | Wrair (Walter Reid Army Institute Of Research) | INDOLO[2,1-b]QUINAZOLE-6,12-DIONE ANTIMALARIAL COMPOUNDS AND METHODS OF TREATING MALARIA THEREWITH |
| WO2004064759A2 (en) * | 2003-01-21 | 2004-08-05 | Chiron Corporation | Use of tryptanthrin compounds for immune potentiation |
| US20040241192A1 (en) * | 2003-01-21 | 2004-12-02 | Chiron Corporation | Use of tryptanthrin compounds for immune potentiation |
| CN103054870A (en) * | 2013-01-08 | 2013-04-24 | 复旦大学 | Use of tryptanthrin compound as indoleamine 2,3-dioxygenase (IDO) inhibitor |
| CN105153148A (en) * | 2015-06-18 | 2015-12-16 | 玉林师范学院 | Tryptanthrin alkaloid salt, and preparation method and application thereof |
| CN105330666A (en) * | 2015-11-27 | 2016-02-17 | 西北大学 | Novel tryptanthrin derivative, synthetic method and medicinal application thereof |
| CN107260743A (en) * | 2016-04-05 | 2017-10-20 | 北京大学 | Azatryptamine ketone derivatives as IDO1 and/or TDO inhibitor purposes |
| CN108969522A (en) * | 2017-06-05 | 2018-12-11 | 复旦大学 | Purposes of the N- benzyl tryptamines ketones derivant as tryptophan dioxygenase (TDO) inhibitor |
| CN109956942A (en) * | 2017-12-25 | 2019-07-02 | 上海翔锦生物科技有限公司 | Tryptamines ketones derivant and application thereof |
| CN110143964A (en) * | 2019-06-17 | 2019-08-20 | 西北大学 | Tryptamines ketone derivatives and its pharmaceutical usage |
| CN114805353A (en) * | 2022-01-11 | 2022-07-29 | 贵州大学 | Synthesis of azatryptanthrin derivative and application of azatryptanthrin derivative in prevention and treatment of plant pathogenic bacteria, fungi bactericide and anti-plant virus preparation |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115710276A (en) * | 2022-11-21 | 2023-02-24 | 贵州大学 | 7-fatty amine substituted tryptanthrin derivative, preparation method and application thereof |
| CN115710276B (en) * | 2022-11-21 | 2024-04-05 | 贵州大学 | 7-fatty amine substituted tryptamine ketone derivative, preparation method and application thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Vicini et al. | Synthesis and antiproliferative activity of benzo [d] isothiazole hydrazones | |
| Cao et al. | Synthesis and structure–activity relationships of harmine derivatives as potential antitumor agents | |
| Zhu et al. | Design, synthesis, and evaluation of chalcone analogues incorporate α, β-Unsaturated ketone functionality as anti-lung cancer agents via evoking ROS to induce pyroptosis | |
| CN102268191B (en) | Heptamethine indocyanine dye, synthetic method thereof and applications thereof | |
| EP3070089A1 (en) | N-benzyl tryptanthrin derivative, and preparation method and application thereof | |
| CN109134586B (en) | Tripterine derivative and application thereof | |
| Hong et al. | Indole derivatives as tubulin polymerization inhibitors for the development of promising anticancer agents | |
| Ismail et al. | Novel synthesis of pyrrolo [2, 3-d] pyrimidines bearing sulfonamide moieties as potential antitumor and radioprotective agents | |
| CN115197227A (en) | Tryptanthrin 1-position or 3-position substituted aromatic thioether derivative, and preparation method and application thereof | |
| He et al. | Organocatalytic asymmetric synthesis of multifunctionalized α-carboline-spirooxindole hybrids that suppressed proliferation in colorectal cancer cells | |
| CN115124531A (en) | 4-azatryptanthrin aromatic thioether derivatives, and preparation method and application thereof | |
| EP3403651B1 (en) | Isocorydine derivatives, preparation method and use thereof | |
| CN104926814A (en) | Matrine derivative and application thereof | |
| CN112480140B (en) | C5-substituted tetrandrine derivative and preparation method and application thereof | |
| Rumalla et al. | Alkaloids from Heimia salicifolia | |
| Mane et al. | Design, synthesis, molecular docking, anti-proliferative and anti-TB studies of 2H-chromen-8-azaspiro [4.5] decane-7, 9-dione conjugates | |
| Yıldız et al. | Exploration of brominated Plastoquinone analogs: Discovery and structure-activity relationships of small antimicrobial lead molecules | |
| Guda et al. | Design, synthesis and biological evaluation of 8-substituted-6-hydrazonoindolo [2, 1-b] quinazolin-12 (6H)-one scaffolds as potential cytotoxic agents: IDO-1 targeting molecular docking studies | |
| WO2011131102A1 (en) | Preparation method of lactone and use thereof | |
| CN104592091A (en) | Compound containing Indole acetic acid core structure and application of compound | |
| CN103864642B (en) | Rhein derivatives and preparation method and use thereof | |
| CN104098457B (en) | Tetrahydrocurcumin analogue, preparation and application thereof | |
| CN105693738A (en) | 3'-phenyl spirono[indoline-3, 2'-pyrrolidine]-2-ketone derivative and preparation method and application thereof | |
| CN108690033B (en) | Fluorescent probe containing flavonoid drug active molecules and preparation method and application thereof | |
| US10703717B2 (en) | Water-soluble isatin derivative, and manufacturing method and application thereof |
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 |