CN113801110A - 1,2, 4-oxadiazole heterocyclic compound and application thereof - Google Patents
1,2, 4-oxadiazole heterocyclic compound and application thereof Download PDFInfo
- Publication number
- CN113801110A CN113801110A CN202111263558.5A CN202111263558A CN113801110A CN 113801110 A CN113801110 A CN 113801110A CN 202111263558 A CN202111263558 A CN 202111263558A CN 113801110 A CN113801110 A CN 113801110A
- Authority
- CN
- China
- Prior art keywords
- compound
- atom
- cells
- cancer cells
- tumor cells
- 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.)
- Granted
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (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)
Abstract
The invention relates to a1, 2, 4-oxadiazole heterocyclic compound and application thereof, belonging to the technical field of antitumor drugs. The invention solves the technical problem of providing a novel compound with an inhibiting effect on tumor cells. The compound has a structural formula shown in a formula I, wherein X is a carbon atom or a nitrogen atom, and R is selected from C1-C4 alkyl, C1-C4 alkoxy or a halogen atom. The invention synthesizes a series of new compounds, finds that the compounds have inhibition effect on the growth of tumor cells, particularly on liver cancer cells and breast cancer cells, have good inhibition effect, can be applied to antitumor drugs and resist tumorThe research and development of new tumor medicines lay a foundation.
Description
Technical Field
The invention relates to a1, 2, 4-oxadiazole heterocyclic compound and application thereof, belonging to the technical field of antitumor drugs.
Background
According to the World Health Organization (WHO) statistics, 3/5 people die from 4 major diseases including cancer, diabetes, cardiovascular disease and chronic respiratory disease worldwide, and cancer is one of the leading causes of death. At present, the treatment methods of cancer mainly include surgical treatment, radiotherapy, chemotherapy, biological immunotherapy, microwave therapy, laser therapy and the like. The chemotherapy mainly uses chemical drugs to kill tumor cells, inhibit the growth and reproduction of the tumor cells and promote the differentiation of the tumor cells, is a systemic treatment means, and has treatment effects on primary foci, metastatic foci and subclinical metastatic foci.
Cisplatin, also known as cis-diamminedichloroplatinum, is a platinum-containing anticancer drug that can be cross-linked to DNA strands and exhibits cytotoxic effects. After dissolution, the cell membrane can pass through the charged cell membrane without carrier transportation in vivo. Because the concentration of intracellular chloride ions is low, the chloride ions are replaced by water, the charges are positive, the double-function groups have the functions similar to double-function groups of an alkylating agent, and can be combined with basic groups of DNA in cell nucleus to form three forms of cross-linking, thereby causing DNA damage, destroying DNA replication and transcription, and inhibiting the synthesis of RNA and protein at high concentration. Cisplatin has the advantages of wide anticancer spectrum, effectiveness of hypoxic cells, strong action and the like, is widely used for treating testicular cancer, ovarian cancer, uterine cancer, bladder cancer, neck cancer, prostatic cancer, brain cancer and the like, and has obvious curative effect. However, cisplatin has certain toxicity when being used for treating cancer, and drug resistance generated by long-term administration is also a problem which is difficult to solve. Therefore, new antitumor drugs with similar clinical effects to cisplatin are continuously sought.
Disclosure of Invention
In view of the above disadvantages, the technical problem to be solved by the present invention is to provide a novel compound having an inhibitory effect on tumor cells.
The compound of the invention has a structural formula shown as a formula I:
wherein, X is carbon atom or nitrogen atom, R is selected from C1-C4 alkyl, C1-C4 alkoxy or halogen atom.
In one embodiment of the invention, X is a carbon atom or a nitrogen atom and R is selected from a methyl group, an ethyl group, a methoxy group, an ethoxy group, an isopropyl group, a fluorine atom or a chlorine atom.
Preferred structural formulae for the compounds of the present invention are any of the following:
as a most preferred example, the compound has the formula
The invention also provides pharmaceutically acceptable salts of the compounds of the invention.
The compound of the invention can be prepared into pharmaceutically acceptable salts, such as nitrate, hydrochloride and the like.
The invention also provides application of the compound in preparing a medicament for inhibiting tumor cell growth.
The compound of the invention has an inhibitory effect on various tumor cells, and in a preferred embodiment of the invention, the tumor cells are liver cancer cells or breast cancer cells.
The invention also provides an anti-tumor pharmaceutical composition.
The active ingredient of the antitumor pharmaceutical composition comprises an effective dose of the compound or the pharmaceutically acceptable salt thereof.
Compared with the prior art, the invention has the following beneficial effects:
the invention synthesizes a series of new compounds, finds that the compounds have inhibition effect on the growth of tumor cells, particularly on liver cancer cells and breast cancer cells, have good inhibition effect, can be applied to antitumor drugs, and lays a foundation for the research and development of new antitumor drugs.
Detailed Description
The compound is a1, 2, 4-oxadiazole heterocyclic compound, and the structural formula of the compound is shown as the formula I:
wherein, X is carbon atom or nitrogen atom, R is selected from C1-C4 alkyl, C1-C4 alkoxy or halogen atom.
The invention synthesizes a series of new compounds, finds that the compounds have inhibition effect on the growth of tumor cells, particularly on liver cancer cells and breast cancer cells, have good inhibition effect, and can be applied to antitumor drugs.
In one embodiment of the invention, X is a carbon atom or a nitrogen atom and R is selected from a methyl group, an ethyl group, a methoxy group, an ethoxy group, an isopropyl group, a fluorine atom or a chlorine atom.
Preferred structural formulae for the compounds of the present invention are any of the following:
as a most preferred example, the compound has the formula
The compound of the invention can be prepared into pharmaceutically acceptable salts, such as nitrate, hydrochloride and the like.
The compound of the invention has inhibitory effect on various tumor cells, such as human colon cancer cells, including HCT116, Sw480, Sw620 and the like; human breast cancer cells including MCF-7, MDA-MB-231, A2870S, and the like; human liver cancer cells including HepG2 and HCC-LM3, etc.; human cervical cancer cell HeLa, etc.; human ovarian cancer cells SKOV-3; human melanoma cells a875 and a375, etc.; human prostate cancer cell PC-3, etc.; human glioma cells U87 and the like.
In a preferred embodiment of the present invention, the tumor cell is a liver cancer cell or a breast cancer cell.
The active ingredient of the antitumor pharmaceutical composition comprises an effective dose of the compound or the pharmaceutically acceptable salt thereof.
The compounds of the present invention may be used alone or in combination with a pharmaceutically acceptable carrier or excipient in the form of a pharmaceutical composition, and when used in the form of a pharmaceutical composition, a therapeutically effective amount of the compound of the present invention or a pharmaceutically acceptable salt thereof is usually combined with at least one pharmaceutically acceptable carrier or diluent and formulated into a suitable dosage form for use.
The anti-tumor pharmaceutical composition can be applied in any mode as follows: oral, aerosol inhalation, rectal administration, nasal administration, parenteral administration such as subcutaneous, intravenous, intramuscular, intraperitoneal, intrapin, intraventricular, intrasternal or intracranial injection or infusion, or by means of an explanted reservoir, with oral, intramuscular, intraperitoneal or intravenous administration being preferred.
The "C1-C4 alkyl" refers to alkyl with 1-4 carbon atoms, including but not limited to methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl and the like.
"C1-C4 alkoxy" refers to alkoxy having 1-4 carbon atoms, and includes, but is not limited to, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, tert-butoxy, and the like.
The following examples are provided to further illustrate the embodiments of the present invention and are not intended to limit the scope of the present invention.
Synthesis of the Compound of example 1
The synthetic route of the compound is as follows:
the specific synthesis method comprises the following steps:
at room temperature, 4-hydroxypiperidine (a) and di-tert-butyl dicarbonate (b) are dissolved in Tetrahydrofuran (THF) at a ratio of 1:1, and 3 times the amount of triethylamine (Et)3N), stirring for 8 hours at normal temperature (rt); after the reaction was completed, the product was separated by column chromatography to give a colorless oily substance c.
And (3) slowly adding NaH into a THF (tetrahydrofuran) solution of the c and bromoacetic acid under an ice bath, adjusting the pH to be acidic by using dilute hydrochloric acid after the reaction is finished, treating the reaction, and separating by using column chromatography to obtain a yellow solid d.
And e is added into the mixed solution of water and ethanol in equal proportion, hydroxylamine hydrochloride is added, and the mixture is stirred at the temperature of 80 ℃. And after the reaction is completed, performing column chromatography separation to obtain white powder f.
Adding f, g and isobutyl chloroformate into toluene in equal proportion, stirring, and adding triethylamine in three times; after the reaction is finished, performing column chromatography separation to obtain white powder of the target molecule.
Wherein, according to the difference of R and X, compounds shown in Table 1 are respectively synthesized:
TABLE 1
The nuclear magnetic characterization results were as follows:
compound a1:
1H NMR(400MHz,Chloroform)δ＝7.98(dt,J＝7.4,1.4,1H),7.72(t,J＝1.4,1H),7.45(t, J＝7.5,1H),7.17(dt,J＝7.5,1.4,1H),4.57(s,2H),3.85(dt,J＝12.4,5.5,2H),3.59(p,J＝7.5,1H), 3.37(dt,J＝12.4,5.5,2H),2.50(s,3H),2.20(ddt,J＝12.9,7.5,5.5,2H),1.78(ddt,J＝12.8,7.5,5.5, 2H),1.49(s,9H).
compound a2:
1H NMR(400MHz,Chloroform)δ＝7.76(dt,J＝7.5,1.5,1H),7.39(t,J＝7.5,1H),7.28(t, J＝1.4,1H),7.02(dt,J＝7.4,1.4,1H),4.58(s,2H),3.91–3.80(m,5H),3.63(p,J＝7.5,1H),3.37(dt, J＝12.3,5.4,2H),2.21(ddt,J＝12.9,7.5,5.4,2H),1.76(ddt,J＝12.8,7.5,5.4,2H),1.49(s,9H).
compound a3:
1H NMR(400MHz,Chloroform)δ＝7.99(dt,J＝7.5,1.5,1H),7.85(t,J＝1.4,1H),7.49(t, J＝7.5,1H),7.35(dt,J＝7.5,1.4,1H),4.58(s,2H),3.85(dt,J＝12.3,5.4,2H),3.63(p,J＝7.5,1H), 3.37(dt,J＝12.3,5.4,2H),2.98(dt,J＝12.8,6.4,1H),2.21(ddt,J＝12.9,7.5,5.4,2H),1.76(ddt, J＝12.8,7.5,5.5,2H),1.49(s,9H),1.26(d,J＝6.4,6H).
compound a4:
1H NMR(400MHz,Chloroform)δ＝7.86(dt,J＝7.4,1.4,1H),7.56–7.43(m,2H),7.20(ddd, J＝9.1,2.8,1.4,1H),4.57(s,2H),3.85(dt,J＝12.4,5.4,2H),3.60(p,J＝7.5,1H),3.37(dt,J＝12.4, 5.5,2H),2.20(ddt,J＝12.9,7.5,5.5,2H),1.78(ddt,J＝12.9,7.5,5.5,2H),1.49(s,9H).
compound B1:
1H NMR(400MHz,Chloroform)δ＝8.67(d,J＝7.5,1H),7.96(dd,J＝7.5,1.5,1H),7.68(d, J＝1.4,1H),4.57(s,2H),3.85(dt,J＝12.3,5.4,2H),3.62(p,J＝7.5,1H),3.37(dt,J＝12.4,5.5,2H), 2.71(s,3H),2.21(ddt,J＝12.9,7.6,5.5,2H),1.76(ddt,J＝12.9,7.6,5.5,2H),1.49(s,9H).
compound B2:
1H NMR(400MHz,Chloroform)δ＝7.70(d,J＝7.5,1H),7.22(dd,J＝7.5,1.4,1H),6.35(d, J＝1.4,1H),4.60(s,2H),3.96(s,3H),3.94–3.78(m,3H),3.38(dt,J＝12.4,5.5,2H),2.08(ddt, J＝12.7,7.3,5.4,2H),1.84(ddt,J＝12.7,7.4,5.5,2H),1.42(s,9H).
compound B3:
1H NMR(400MHz,Chloroform)δ＝8.63(d,J＝7.5,1H),7.99(dd,J＝7.5,1.4,1H),7.71(d, J＝1.4,1H),4.57(s,2H),3.85(dt,J＝12.3,5.5,2H),3.62(p,J＝7.5,1H),3.43–3.23(m,3H),2.20 (ddt,J＝12.9,7.5,5.4,2H),1.76(ddt,J＝12.8,7.5,5.4,2H),1.49(s,9H),1.34(d,J＝6.4,6H).
compound B4:
1H NMR(400MHz,Chloroform)δ＝8.30(d,J＝7.5,1H),8.17(dd,J＝7.5,1.4,1H),7.50(dd, J＝7.9,1.4,1H),4.57(s,2H),3.85(dt,J＝12.3,5.4,2H),3.62(p,J＝7.5,1H),3.37(dt,J＝12.4,5.5, 2H),2.21(ddt,J＝12.9,7.5,5.4,2H),1.76(ddt,J＝12.9,7.5,5.5,2H),1.49(s,9H).
example 2 antitumor Activity assay
Tumor cells selected for the experiments were: human colon cancer cells including HCT116, Sw480 and Sw 620; human breast cancer cells, including MCF-7 and MDA-MB-231; human liver cancer cells, including HepG2 and HCC-LM 3; human cervical cancer cell HeLa; human ovarian cancer cells SKOV-3; human melanoma cells a875 and a 375; human prostate cancer cell PC-3; human glioma cells U87. All of the above cells were purchased from ATCC.
The experimental method comprises the following steps:
tumor cells in the logarithmic growth phase were taken, digested with trypsin, centrifuged and resuspended in fresh medium, and the cells were seeded at the appropriate density in 96-well plates at 100. mu.L per well of medium. After inoculation, the 96-well plate is placed in an incubator to continue culturing for 24h, so that the tumor cells adhere to the wall. And (3) culture environment: temperature 37 ℃ and 5% CO2. Adding medicine when the cells adhere to the wall and reach the proper cell density, stopping the experiment after 72h, adding 20 mu L of CCK8 solution, and putting the mixture into a cell culture box for acting for 2-4 h. The absorbance value (OD value) of each well at 450nm is measured by using a microplate reader, and the in vitro proliferation inhibition rate and the cell survival rate of the tumor cells in each experimental group are calculated. According to the formula: relative cell proliferation inhibition (%) (blank control-experimental group)/blank control group × 100%. Each set was provided with 3 parallel replicates and each experiment was repeated three times. Finally using IC50Computing software to solve for IC50(half inhibitory concentration, in. mu. mol/L).
The results are shown in Table 2.
TABLE 2
Therefore, the compound has an inhibiting effect on various tumor cells, particularly the compound A3 has a good inhibiting effect on liver cancer cells HepG2 and breast cancer cells MCF-7, the half inhibiting concentration of the compound is even lower than that of cisplatin, the compound is shown to have a good cell inhibiting effect, and the compound can be used for preparing medicines for treating liver cancer or breast cancer, and lays a foundation for new anti-tumor medicines.
Claims (8)
1. A compound of formula I:
wherein, X is carbon atom or nitrogen atom, R is selected from C1-C4 alkyl, C1-C4 alkoxy or halogen atom.
2. The compound of claim 1, wherein: x is carbon atom or nitrogen atom, R is selected from methyl, ethyl, methoxyl, ethoxyl, isopropyl, fluorine atom or chlorine atom.
3. The compound of claim 1, wherein: the structural formula is any one of the following structural formulas:
4. a compound according to claim 3, characterized in that: the structural formula is
5. A pharmaceutically acceptable salt of a compound according to any one of claims 1 to 4.
6. Use of a compound according to any one of claims 1 to 4 in the manufacture of a medicament for inhibiting the growth of tumour cells.
7. Use according to claim 6, characterized in that: the tumor cell is liver cancer cell or breast cancer cell.
8. A pharmaceutical composition for treating cancer, comprising: the active ingredient of which comprises an effective dose of a compound as claimed in any one of claims 1 to 4 or a pharmaceutically acceptable salt thereof.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111263558.5A CN113801110B (en) | 2021-10-28 | 2021-10-28 | 1,2, 4-oxadiazole heterocyclic compound and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111263558.5A CN113801110B (en) | 2021-10-28 | 2021-10-28 | 1,2, 4-oxadiazole heterocyclic compound and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN113801110A true CN113801110A (en) | 2021-12-17 |
| CN113801110B CN113801110B (en) | 2023-07-18 |
Family
ID=78938240
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202111263558.5A Active CN113801110B (en) | 2021-10-28 | 2021-10-28 | 1,2, 4-oxadiazole heterocyclic compound and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN113801110B (en) |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1898235A (en) * | 2003-12-24 | 2007-01-17 | 普罗西迪恩有限公司 | Heterocyclic derivatives as gpcr receptor agonists |
| CN101460493A (en) * | 2006-04-06 | 2009-06-17 | 普罗西迪恩有限公司 | Heterocyclic Gpcr agonists |
| CN105980363A (en) * | 2014-02-18 | 2016-09-28 | 第三共株式会社 | Aminopyrazolone derivative |
| CN113149980A (en) * | 2020-01-07 | 2021-07-23 | 上海市奉贤区中心医院 | Tert-butyloxycarbonyl micromolecule organic compound targeting PUF60, derivative thereof and application thereof |
-
2021
- 2021-10-28 CN CN202111263558.5A patent/CN113801110B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1898235A (en) * | 2003-12-24 | 2007-01-17 | 普罗西迪恩有限公司 | Heterocyclic derivatives as gpcr receptor agonists |
| CN101460493A (en) * | 2006-04-06 | 2009-06-17 | 普罗西迪恩有限公司 | Heterocyclic Gpcr agonists |
| CN105980363A (en) * | 2014-02-18 | 2016-09-28 | 第三共株式会社 | Aminopyrazolone derivative |
| CN113149980A (en) * | 2020-01-07 | 2021-07-23 | 上海市奉贤区中心医院 | Tert-butyloxycarbonyl micromolecule organic compound targeting PUF60, derivative thereof and application thereof |
Non-Patent Citations (1)
| Title |
|---|
| HILARY A. OVERTON，等: "Deorphanization of a G protein-coupled receptor for oleoylethanolamide and its use in the discovery of small-molecule hypophagic agents", 《CELL METABOLISM》 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN113801110B (en) | 2023-07-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN104230952A (en) | Compound containing pyrimidine skeleton, and preparation method and use of compound | |
| AU2021105895A4 (en) | Lycoline B-aryl acrylate derivatives, preparation method and application thereof | |
| CN102627685B (en) | Nitric oxide-donating glutathione compound, preparation method and medical purpose thereof | |
| CN104926792A (en) | Metronidazole derivative and preparing method and application thereof | |
| CN104230912B (en) | Quinoline, Its Preparation Method And Use | |
| US20150374646A1 (en) | Treatment of cancer and other conditions using a transcription factor modulator | |
| CN112334458B (en) | 3-indazolinone compound, preparation method and application thereof in medicine and pharmacology | |
| CN101475506A (en) | Higher fatty acid derivative novel compound, and its preparation and antineoplastic use | |
| CN113801110B (en) | 1,2, 4-oxadiazole heterocyclic compound and application thereof | |
| CN108358894B (en) | Compound for inhibiting histone acetyltransferase as well as preparation method and application thereof | |
| US9499552B2 (en) | Pyrazolo[1,5-A]pyrimidine derivative and use of anti-tumor thereof | |
| US20160102066A1 (en) | Benzothiazole derivative and anti-tumor use thereof | |
| CN115677828A (en) | Antitumor m-dichlorophenol derivative and preparation method thereof | |
| EP3880684B1 (en) | In-flow photooxygenation of aminothienopyridinones generates novel ptp4a3 phosphatase inhibitors | |
| CN103012394B (en) | Rhodanine derivative and preparation method thereof | |
| CN107474043A (en) | Nicotinic acid derivates and preparation method thereof and purposes | |
| US11389445B2 (en) | Pentafluorosulfanyl-substituted amide derivatives, preparation methods thereof and medical uses thereof | |
| CN109096194B (en) | Biguanide derivative, pharmaceutical composition, preparation method and application | |
| CN110123811A (en) | Application of the tanshinone IIA derivative in preparation anti-gastric cancer medicament | |
| CN114394934B (en) | Pyrazole benzamide compound as well as preparation method and application thereof | |
| CN104341407A (en) | Quinazoline compounds, preparation method and applications thereof | |
| CN115894607B (en) | Antitumor phenylalanine valyl derivative and preparation method thereof | |
| CN113069451B (en) | Preparation method of pyrrole-2-sulfonamide compound and application of pyrrole-2-sulfonamide compound in preparation of antitumor drugs | |
| CN111253314B (en) | Vinyl sulfonamide substituted pyrazolyl benzamides | |
| CN103709135B (en) | Ton ketone derivatives and its preparation method and application |
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 |