CN110885307B - Cyclic polypeptide 2-styryl-5-pyrrolidone-2-amide derivative, preparation method and application thereof - Google Patents
Cyclic polypeptide 2-styryl-5-pyrrolidone-2-amide derivative, preparation method and application thereof Download PDFInfo
- Publication number
- CN110885307B CN110885307B CN201911154266.0A CN201911154266A CN110885307B CN 110885307 B CN110885307 B CN 110885307B CN 201911154266 A CN201911154266 A CN 201911154266A CN 110885307 B CN110885307 B CN 110885307B
- Authority
- CN
- China
- Prior art keywords
- pyrrolidone
- styryl
- cyclic polypeptide
- para
- amide derivative
- 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
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/34—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/36—Oxygen or sulfur atoms
- C07D207/38—2-Pyrrolones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a cyclic polypeptide 2-styryl-5-pyrrolidone-2-amide derivative, a preparation method and application thereof, belonging to the field of medicine, wherein the cyclic polypeptide 2-styryl-5-pyrrolidone-2-amide derivative can be obtained by using para-fluoroaniline, 3-para-chlorophenyl acrolein, Z-2-bromomethyl-3-para-chlorophenyl acrylic acid and cyclohexyl isonitrile through multi-component condensation and ring-closing series one-pot reaction. Activity tests prove that the cyclic polypeptide 2-styryl-5-pyrrolidone-2-amide derivative obtained by the invention is a suitable candidate anti-tumor drug, and particularly serves as a candidate anti-cervical cancer treatment drug. Compared with a positive control medicament cisplatin, the inhibiting activity of the medicament on cancer cells is improved. The preparation method is simple, raw materials are easy to obtain, the yield of the synthetic route is high, and the operation process is simple and convenient. The compound has wide prospect in the development and application of anti-tumor drugs.
Description
Technical Field
The invention relates to the technical field of medicines, in particular to a cyclopeptide 2-styryl-5-pyrrolidone-2-amide derivative, a preparation method and an application thereof.
Background
The pyrrole ring with high efficiency, low toxicity, broad spectrum and other biological activities widely exists in animal and plant bodies and in microbial metabolites, has wide medical activities including antibacterial, anti-inflammatory, antiviral and antitumor activities, and also has wide pesticide activities including bactericidal and insecticidal activities, plant growth regulating activities, insect repelling, feeding refusal and attracting activities and the like. Pyrrolidones are also an important class of compounds, and derivatives thereof have been reported in the literature to be useful as antimuscarinic, antiepileptic, anti-AIDS and antiviral agents; the pyrrolidone derivatives are used as a very important drug intermediate, have wide application in the fields of medicines, pesticides, chemical engineering and the like, and are widely used for synthesizing anticancer and antiviral active compounds, antihistamines, tachykinin blockers, hypnotic and sedative zopiclone analogues, HIV protease blockers and the like at present.
The pyrrolidone compound is widely applied, but the synthesis method mostly adopts a step method, the synthesis process is complicated, the steps are multiple, and the yield is lower.
Disclosure of Invention
The invention aims to provide a compound which has obvious anti-tumor activity, obvious inhibition effect on cervical cancer cells and capability of increasing the apoptosis rate of tumor cells, and a preparation method and application of the compound.
In order to achieve the purpose, the invention provides the following scheme:
the invention provides a cyclic polypeptide 2-styryl-5-pyrrolidone-2-amide derivative, which has a structural formula shown as a formula I:
the invention also provides a preparation method of the cyclic polypeptide 2-styryl-5-pyrrolidone-2-amide derivative, which is synthesized by a multi-component condensation and ring closing reaction series one-pot method.
Further, the preparation method comprises the following steps:
step one, placing para-fluoroaniline and 3-para-chlorophenyl acrolein in a reaction vessel, adding methanol, and stirring for half an hour;
step two, after the precipitate is generated, adding dried Z-2-bromomethyl-3-p-chlorophenyl acrylic acid and cyclohexyl isonitrile in sequence, and reacting for 24 hours at room temperature;
step three, after the TLC monitors that the polymerization reaction is complete, adding potassium carbonate, heating to 60 ℃, carrying out reflux reaction for 12 hours, and monitoring that the ring closing reaction is complete by TLC;
and step four, filtering, freezing the filtrate in a refrigerator overnight, leaching after the solid is completely separated out, washing with water, and recrystallizing with diethyl ether to obtain the product.
Further, in the first step, the molar ratio of the para-fluoroaniline to the 3-para-chlorophenyl acrolein is 1, and 5ml of methanol is added to each mole of the para-fluoroaniline.
Further, in the second step, the molar ratio of Z-2-bromomethyl-3-p-chlorophenylacrylic acid to cyclohexylisonitrile is 1.
Further, the molar ratio of the potassium carbonate to the para-fluoroaniline in the step three is 1.5.
The invention provides a pharmaceutical composition containing cyclic polypeptide 2-styryl-5-pyrrolidone-2-amide, which comprises 0.01-5% of cyclic polypeptide 2-styryl-5-pyrrolidone-2-amide derivatives and 95-99.99% of pharmaceutically acceptable auxiliary materials.
The invention provides an injection composition containing cyclic polypeptide 2-styryl-5-pyrrolidone-2-amide derivatives, which comprises 0.01-5% of cyclic polypeptide 2-styryl-5-pyrrolidone-2-amide derivatives and 95-99.99% of pharmaceutically acceptable auxiliary materials, wherein the pharmaceutically acceptable auxiliary materials comprise a solubilizer.
The pharmaceutically acceptable auxiliary materials also comprise a pH regulator.
The composition for injection is preferably freeze-dried powder injection.
The pH regulator is sodium hydroxide, so that the cyclic polypeptide 2-styryl-5-pyrrolidone-2-amide derivative is converted into a sodium salt form to prepare the lyophilized powder injection. The transition of which is a partial transition or a full transition.
The invention provides a preparation, which comprises the following components in part by weight:
a lyophilized powder for injection is prepared from 0.01-5% cyclopeptide 2-styryl-5-pyrrolidone-2-amide derivatives and 95% -99.99% pharmaceutically acceptable adjuvants; wherein the pharmaceutically acceptable excipient comprises sodium hydroxide as a pH regulator, which is capable of converting the cyclic polypeptide 2-styryl-5-pyrrolidone-2-amide derivative into a sodium salt form. The transition of which is a partial transition or a full transition. The portion is converted to at least 20%, 30%, 40%, 50%, 60% or 80% to the sodium salt form.
The invention also provides application of the cyclic polypeptide 2-styryl-5-pyrrolidone-2-amide derivative in preparation of antitumor drugs.
Further, the tumor is cervical cancer.
The invention discloses the following technical effects:
the invention adopts multi-component condensation and ring closing reaction to synthesize the novel cyclic polypeptide 2-styryl-5-pyrrolidone-2-amide derivative in a one-pot manner in series, and has no intermediate separation step, so the total reaction yield is increased and is 89%, and the reaction steps can be reduced by multi-component condensation to obtain more corresponding functional group substitutions. If the conventional method is used for designing and synthesizing similar polyfunctional group substituted pyrrolidone derivatives, not only the synthesis steps are more, which results in lower total yield, but also part of reaction conditions are more severe. The reaction has high reaction efficiency, and avoids the loss and trouble of separating an intermediate; has the characteristics of mild reaction conditions, high yield, simple and convenient operation, little environmental pollution and the like.
The activity test proves that the cyclic polypeptide 2-styryl-5-pyrrolidone-2-amide derivative obtained by the invention is a suitable candidate anti-tumor drug, and especially serves as a candidate drug for anti-cervical cancer treatment. Compared with a positive control medicament cisplatin, the inhibiting activity of the medicament on cancer cells is improved. The cyclic polypeptide 2-styryl-5-pyrrolidone-2-amide derivative has the advantages of simple synthesis method, easily obtained raw materials, high yield of a synthetic route and simple and convenient operation process. The compound has wide prospects in the development and application aspects of antitumor drugs.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings needed to be used in the embodiments will be briefly described below, and it is obvious that the drawings in the following description are only some embodiments of the present invention, and it is obvious for those skilled in the art to obtain other drawings without inventive exercise.
FIG. 1 is a scheme showing the synthesis scheme of the cyclic polypeptide 2-styryl-5-pyrrolidone-2-amide derivatives according to the present invention;
FIG. 2 is a hydrogen spectrum of a cyclic polypeptide 2-styryl-5-pyrrolidone-2-amide derivative according to example 1 of the present invention;
FIG. 3 shows the migration effect of the cyclic polypeptide 2-styryl-5-pyrrolidone-2-amide derivatives on cervical cancer C-33A cells;
FIG. 4 shows the effect of the cyclic polypeptide 2-styryl-5-pyrrolidone-2-amide derivatives of the present invention on apoptosis factors Bax and Caspase-3.
Detailed Description
Reference will now be made in detail to various exemplary embodiments of the invention, the detailed description should not be construed as limiting the invention but as a more detailed description of certain aspects, features and embodiments of the invention.
It is to be understood that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. Further, for numerical ranges in this disclosure, it is understood that each intervening value, between the upper and lower limit of that range, is also specifically disclosed. Every smaller range between any stated value or intervening value in a stated range and any other stated or intervening value in a stated range is encompassed within the invention. The upper and lower limits of these smaller ranges may independently be included or excluded in the range.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although only preferred methods and materials are described herein, any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention. All documents mentioned in this specification are incorporated by reference herein for the purpose of disclosing and describing the methods and/or materials associated with the documents. In case of conflict with any incorporated document, the present specification will control.
It will be apparent to those skilled in the art that various modifications and variations can be made in the specific embodiments of the present disclosure without departing from the scope or spirit of the disclosure. Other embodiments will be apparent to those skilled in the art from consideration of the specification. The specification and examples are exemplary only.
As used herein, the terms "comprising," "including," "having," "containing," and the like are open-ended terms that mean including, but not limited to.
EXAMPLE 1 preparation of cyclopolypeptide 2-styryl-5-pyrrolidone-2-amide derivatives
Weighing para-fluoroaniline (1 mmol) and 3-para-chlorophenyl acrolein(1 mmol) adding 5mL of methanol into a 25mL round-bottom flask, stirring for half an hour, after a precipitate is generated, sequentially adding dried Z-2-bromomethyl-3-p-chlorophenyl acrylic acid (1 mmol) and cyclohexyl isonitrile (1 mmol), and reacting for 24 hours at room temperature; after TLC monitoring polymerization reaction is completed, adding potassium carbonate (1.5 mmol), heating to 60 ℃, refluxing for reaction for 12 hours, and after TLC monitoring ring-closing reaction is completed; filtering, freezing the filtrate in a refrigerator overnight, filtering after the solid is completely separated out, washing with water, and recrystallizing with diethyl ether to obtain cyclopolypeptide 2-styryl-5-pyrrolidone-2-amide derivative with total yield of 89%. The cyclic polypeptide 2-styryl-5-pyrrolidone-2-amide derivatives prepared in this example have the structural formula shown in formula I, and the cyclic polypeptide 2-styryl-5-pyrrolidone-2-amide derivatives obtained in this example have the chemical name of 4E-N-cyclohexyl-2-p-chlorostyryl-1-p-fluorophenyl-4-p-chlorobenzylidene-5-pyrrolidone-2-amide, and the spectral data thereof are as follows: white solid (0.50 g, total yield: 89%). Melting point: 128-130 ℃. 1 H NMR(CDCl 3 ,600MHz):δ7.55-6.98(m,14H,12Ar-H and 2＝CH),6.34(d,J＝16.2Hz,1H,＝CH),5.68(s,1H,NH),3.74-3.72(m,1H,NCH),3.45(d,J＝16.8Hz,1H,CH 2 a ),3.33(d,J＝16.8Hz,1H,CH 2 b ),1.77-0.80(m,10H,5CH 2 ).IR(KBr)1707,1643(C＝O)cm- 1 .MS m/z(％):562(M + ,2),436(21),341(45),95(100).Anal.Calcd for C 32 H 29 C l2 FN 2 O 2 C,68.21; h,5.19; n,4.97; found C,68.03; h,5.26; n,4.91. It 1 The H NMR spectrum is shown in FIG. 2.
Comparative experiment: as in the above experimental procedure, K used in the ring closure reaction 2 CO 3 The overall yields were compared for the other bases and are shown in table 1. As can be seen from Table 1, the yields were best using potassium carbonate and cesium carbonate, but potassium carbonate was more economical to select.
Table 1: synthesis condition optimization of cyclic polypeptide 2-styryl-5-pyrrolidone-2-amide derivative
EXAMPLE 2 Effect of cyclopolypeptide 2-styryl-5-pyrrolidone-2-amide derivatives on proliferation of cervical cancer C-33A cells
Cervical cancer cells C-33A in the logarithmic growth phase were collected, digested with 0.25% trypsin, and then centrifuged. Pouring off cell supernatant, preparing single cell suspension with DMEM medium containing 10% fetal calf serum, adjusting cell suspension concentration to 2 × 10 per ml 5 Individual C-33A cells were seeded into 96-well plates and cultured, 200 μ L of cell suspension was added per well, and the edges of the 96-well plates were filled with sterile PBS. In 5% of CO 2 And incubating in an incubator at 37 ℃ for 24h. Blanks were set and the cyclopeptide 2-styryl-5-pyrrolidone-2-amide derivatives at different concentrations of 3.125, 6.25, 12.5, 25, 50, 100 μ M and cisplatin were treated for 48h in logarithmic growth phase C-33A cells, respectively. Then, MTT reagent was added, and the absorbance was measured with a microplate reader to determine the inhibition ratio at each concentration. The inhibition rate at each concentration is shown in table 2.
TABLE 2 inhibitory Rate of Cyclic polypeptide 2-styryl-5-pyrrolidone-2-amide derivatives and cisplatin on C-33A cells
Note: n =3, # P <0.05, # P <0.01, compared to control 1.
As can be seen from Table 2, the cyclic polypeptide 2-styryl-5-pyrrolidone-2-amide derivatives and cisplatin suppressed the proliferation of cervical cancer cells C-33A, and the cyclic polypeptide 2-styryl-5-pyrrolidone-2-amide derivatives had a better inhibitory effect than cisplatin.
According to the results of the MTT method, the cervical cancer cell inhibition rate is remarkably increased with the increase of the concentration of the cyclic polypeptide 2-styryl-5-pyrrolidone-2-amide derivative. The concentration of the cyclic polypeptide 2-styryl-5-pyrrolidone-2-amide derivative is from 3.125 mu M to 100 mu M, and the inhibition rate of the cervical cancer cells C-33A is respectively increased from (18.62% + -3.20%) to (94.68% + -0.19%).
EXAMPLE 3 Effect of cyclopolypeptide 2-styryl-5-pyrrolidone-2-amide on apoptosis of cervical cancer C-33A cells
Cervical cancer cells C-33A in the logarithmic growth phase were collected, digested with 0.25% trypsin, and then centrifuged. Pouring off cell supernatant, preparing into single cell suspension with DMEM medium containing 10% fetal calf serum, and adjusting cell suspension concentration to contain 2 × 10 per ml 5 For each C-33A cell, 2mL of cell suspension was added per well of 6-well plate. 5% of CO 2 Incubate at 37 ℃ for 24h. Setting blank control group, and IC of C-33A cell according to cyclic polypeptide 2-styryl-5-pyrrolidone-2-amide derivative 50 Size settings of (2. Mu.M, 4. Mu.M, 6. Mu.M) cells were treated for 48h at low, medium and high concentrations, respectively. After 48h, the cells were harvested, digested with 0.25% trypsin without EDTA and then centrifuged. The operation is carried out according to the specification of the rhAnnexin V-FITC apoptosis detection kit, and the effect of the cyclopolypeptide 2-styryl-5-pyrrolidone-2-amide derivative on the apoptosis of the C-33A cells is measured by a flow cytometer. The apoptosis rate of the cells is shown in table 3.
TABLE 3 Effect of cyclopolypeptide 2-styryl-5-pyrrolidone-2-amide derivatives on apoptosis of C-33A cells
Note: n =3, P <0.01 in comparison with the control group
As can be seen from Table 3, the apoptosis rate of C-33A cells increased from 7.38% to 28.92% in the flow cytometry results.
EXAMPLE 4 Effect of the Cyclic polypeptide 2-styryl-5-pyrrolidone-2-amide on C-33A cell migration
Cervical cancer cells C-33A in the logarithmic growth phase were collected, digested with 0.25% trypsin, and then centrifuged. Pouring off cell supernatant, preparing single cell suspension with DMEM medium containing 10% fetal calf serum, adjusting cell suspension concentration to 2 × 10 per ml 5 For each C-33A cell, 2mL of cell suspension was added per well of 6-well plate. 5% of CO 2 And incubating in an incubator at 37 ℃ for 24h. Until the cells are fused to about 70 percentThe cell supernatant was aspirated by placing a previously sterilized ruler above the six-well plate, drawing three straight lines in each well with a 200 μ L tip, washing twice with PBS, and taking a picture under a microscope. The blank control group and the cyclopeptide 2-styryl-5-pyrrolidone-2-amide derivatives with different concentrations of 4. Mu.M, 6. Mu.M, 8. Mu.M and 10. Mu.M were set to treat the cells for 0h, 24h, 48h and 72h respectively, and the migration of the cells was observed by photographing under a microscope, and the migration results are shown in FIG. 3.
According to the migration results shown in FIG. 3, the cyclic polypeptide 2-styryl-5-pyrrolidone-2-amide derivatives can inhibit cell migration to different degrees after acting on the cervical cancer C-33A cells for 0h, 24h, 48h and 72h compared with the scratch width of the control group after acting on the cervical cancer C-33A cells with different concentrations of the cyclic polypeptide 2-styryl-5-pyrrolidone-2-amide derivatives.
EXAMPLE 5 Effect of the Cyclic polypeptide 2-styryl-5-pyrrolidone-2-amide on apoptosis factors Bax, caspase-3
Cervical cancer cells C-33A in the logarithmic growth phase were collected, digested with 0.25% trypsin, and then centrifuged. Pouring off cell supernatant, preparing into single cell suspension with DMEM medium containing 10% fetal calf serum, and adjusting cell suspension concentration to contain 2 × 10 per ml 5 For each C-33A cell, 2mL of cell suspension was added per well of 6-well plate. 5% of CO 2 And incubating in an incubator at 37 ℃ for 24h. Setting blank control group and different concentrations of cyclopeptide 2-styryl-5-pyrrolidone-2-amide derivatives of 4 muM, 6 muM and 8 muM to treat the cells for 48h respectively. After 48h, the cells were harvested, total RNA was extracted from the cells, and then RT-q PCR was performed. The results were calculated from the CT values obtained by amplification, and the amplification results are shown in FIG. 4. As can be seen from FIG. 4, expression of both Bax and Caspase-3 was increased, and both were pro-apoptotic genes. The experimental result shows that the cyclopeptide 2-styryl-5-pyrrolidone-2-amide derivative can induce apoptosis by promoting the expression of apoptosis promoting genes Bax and Caspase-3.
The above-described embodiments are only intended to illustrate the preferred embodiments of the present invention, and not to limit the scope of the present invention, and various modifications and improvements made to the technical solution of the present invention by those skilled in the art without departing from the spirit of the present invention should fall within the protection scope defined by the claims of the present invention.
Claims (7)
1. A cyclic polypeptide 2-styryl-5-pyrrolidone-2-amide derivative is characterized in that the structural formula is shown as formula I:
2. the method for preparing cyclic polypeptide 2-styryl-5-pyrrolidone-2-amide derivatives according to claim 1, comprising the steps of:
step one, placing para-fluoroaniline and 3-para-chlorophenyl acrolein in a reaction vessel, adding methanol, and stirring for half an hour;
step two, after the precipitate is generated, adding dried Z-2-bromomethyl-3-p-chlorophenyl acrylic acid and cyclohexyl isonitrile in sequence, and reacting for 24 hours at room temperature;
step three, after the TLC monitoring polymerization reaction is completed, adding potassium carbonate, heating to 60 ℃, performing reflux reaction for 12 hours, and monitoring the ring closing reaction by TLC to be completed;
and step four, filtering, freezing the filtrate in a refrigerator overnight, leaching after the solid is completely separated out, washing with water, and recrystallizing with diethyl ether to obtain the product.
3. The process for producing a cyclic polypeptide 2-styryl-5-pyrrolidone-2-amide derivative according to claim 2, wherein the molar ratio of para-fluoroaniline to 3-para-chlorophenylacrolein in the first step is 1.
4. The method for preparing cyclic polypeptide 2-styryl-5-pyrrolidone-2-amide derivatives according to claim 2, wherein the molar ratio of Z-2-bromomethyl-3-p-chlorophenylacrylic acid to cyclohexylisonitrile in the second step is 1.
5. The process for preparing cyclic polypeptide 2-styryl-5-pyrrolidone-2-amide derivatives according to claim 2, wherein the molar ratio of potassium carbonate to para-fluoroaniline in step III is 1.5:1.
6. a pharmaceutical composition comprising the cyclic polypeptide 2-styryl-5-pyrrolidone-2-amide derivative of claim 1 and a pharmaceutically acceptable excipient.
7. The cyclic polypeptide 2-styryl-5-pyrrolidone-2-amide derivative according to claim 1, for use in the preparation of an antitumor agent for the treatment of cervical cancer.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911154266.0A CN110885307B (en) | 2019-11-22 | 2019-11-22 | Cyclic polypeptide 2-styryl-5-pyrrolidone-2-amide derivative, preparation method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911154266.0A CN110885307B (en) | 2019-11-22 | 2019-11-22 | Cyclic polypeptide 2-styryl-5-pyrrolidone-2-amide derivative, preparation method and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN110885307A CN110885307A (en) | 2020-03-17 |
| CN110885307B true CN110885307B (en) | 2023-03-17 |
Family
ID=69748310
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201911154266.0A Active CN110885307B (en) | 2019-11-22 | 2019-11-22 | Cyclic polypeptide 2-styryl-5-pyrrolidone-2-amide derivative, preparation method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN110885307B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113999154B (en) * | 2021-06-23 | 2023-03-21 | 国药东风总医院 | Compound and preparation method and application thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1318541A (en) * | 2000-04-17 | 2001-10-24 | 中国医学科学院药物研究所 | Sulfonyl-containing pyrrolidone compound and preparation method and pharmaceutical application thereof |
| CN101528690A (en) * | 2006-07-12 | 2009-09-09 | 阿斯利康(瑞典)有限公司 | Isoindoline derivatives for the treatment of arrhythmias |
| CN105431436A (en) * | 2013-05-14 | 2016-03-23 | 内尔维阿诺医学科学有限公司 | Pyrrolo[2,3-d]pyrimidine derivatives, process for their preparation and their use as kinase inhibitors |
-
2019
- 2019-11-22 CN CN201911154266.0A patent/CN110885307B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1318541A (en) * | 2000-04-17 | 2001-10-24 | 中国医学科学院药物研究所 | Sulfonyl-containing pyrrolidone compound and preparation method and pharmaceutical application thereof |
| CN101528690A (en) * | 2006-07-12 | 2009-09-09 | 阿斯利康(瑞典)有限公司 | Isoindoline derivatives for the treatment of arrhythmias |
| CN105431436A (en) * | 2013-05-14 | 2016-03-23 | 内尔维阿诺医学科学有限公司 | Pyrrolo[2,3-d]pyrimidine derivatives, process for their preparation and their use as kinase inhibitors |
Non-Patent Citations (2)
| Title |
|---|
| Andrey S. Trifilenkov et al..One-pot tandem complexity-generating reaction based on Ugi four component condensation and intramolecular cyclization.2007,第48卷2563–2567. * |
| Xiao-Hua Zeng et al..One-pot synthesis of 5-oxopyrrolidine-2-carboxamides via a tandem Ugi 4CC/SN cyclization starting from BayliseHillman bromides.2013,第69卷3823-3828. * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN110885307A (en) | 2020-03-17 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN105669565B (en) | Isolonglifolane yl pyrimidines class compound and preparation method and application | |
| CN110627755B (en) | Gamma-butyrolactone dimer anticancer compound and preparation method thereof | |
| CN110885307B (en) | Cyclic polypeptide 2-styryl-5-pyrrolidone-2-amide derivative, preparation method and application thereof | |
| CN107266348A (en) | Preparation, structure and the purposes of the indolecarboxaldehyde Schiff base of 4-acetylbiphenyl hydrazone 3 | |
| Xia et al. | Antimicrobial evaluation and action mechanism of chalcone derivatives containing quinoxaline moiety | |
| CN102838571A (en) | Andrographolide derivative containing gamma-subunit butenolide, synthetic method and application thereof | |
| CN106674182B (en) | Formoononetin derivative, preparation method containing dithiocarbamates and its application in antitumor drug | |
| CN107286220B (en) | 1,2, 4-triazole coupled dihydromyricetin derivative and preparation method and application thereof | |
| CN103102331B (en) | Pharmaceutical application of chalcone compound containing piperazine ring | |
| CN110511214B (en) | Diamine substituted aromatic heterocyclic compound and preparation method and application thereof | |
| CN109438462B (en) | O-p-nitrobenzoyl earthy licorice A with antineoplastic activity and preparation method and application thereof | |
| CN104311598A (en) | Phosphate compound containing 1,2,3-triazole ring as well as preparation method and application thereof | |
| CN109280073A (en) | Nannocystins derivative and application thereof | |
| CN107266349A (en) | Preparation, structure and the purposes of the indolecarboxaldehyde Schiff base of 4-acetylbiphenyl hydrazone 2 | |
| CN113999154B (en) | Compound and preparation method and application thereof | |
| CN112480019B (en) | 2-benzoxazolone derivative of acanthus ilicifolius alkaloid in marine mangrove, and preparation method and application thereof | |
| CN106946974B (en) | Ursolic amide derivative containing pyrazole heterocycle and synthesis and application thereof | |
| CN111217824B (en) | 4-O-arylaminopropyl glycyrrhiza A derivative and preparation and application thereof | |
| CN109988197A (en) | A kind of ferrocene coumarin kind compound and its preparation method and application | |
| CN105968162B (en) | Withanolides type compound and application thereof | |
| CN105367445B (en) | Preparation, structure and application of benzyl dihydrazone-N-mono-(2-hydroxy-4-diethylin-1-formyl benzene) | |
| CN104530062B (en) | A kind of 1,4-naphthoquinone derivatives and synthetic method thereof | |
| CN114957340B (en) | Preparation method and application of binuclear iridium complex for inducing iron death | |
| CN113234063B (en) | Pyrazolyl-asarum derivative, preparation method and application thereof | |
| CN107382941B (en) | Flavone derivative and preparation 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 | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |