CN113754646B - (4- (1, 2, 4-oxadiazol-5-yl) phenyl) carboxamide derivatives and application thereof in anti-arthritis drugs - Google Patents
(4- (1, 2, 4-oxadiazol-5-yl) phenyl) carboxamide derivatives and application thereof in anti-arthritis drugs Download PDFInfo
- Publication number
- CN113754646B CN113754646B CN202110812039.3A CN202110812039A CN113754646B CN 113754646 B CN113754646 B CN 113754646B CN 202110812039 A CN202110812039 A CN 202110812039A CN 113754646 B CN113754646 B CN 113754646B
- Authority
- CN
- China
- Prior art keywords
- phenyl
- oxadiazol
- arthritis
- derivative
- tnf
- 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
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
- C07D413/04—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 directly linked by a ring-member-to-ring-member bond
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- 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
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Abstract
The invention belongs to the field of pharmacotherapeutics, and particularly relates to a medical application of a (4- (1, 2, 4-oxadiazole-5-yl) phenyl) formamide derivative, in particular to an application of the derivative in preparation of a medicament for preventing or treating arthritis. The structural formula of the compound is shown as formula A:researches show that the (4- (1, 2, 4-oxadiazole-5-yl) phenyl) formamide derivative can inhibit the release of NO, IL-1 beta and TNF-alpha, relieve the symptoms of an adjuvant type arthritis rat model and has the potential of developing into an anti-arthritis drug.
Description
Technical Field
The invention belongs to the field of pharmacotherapeutics, and particularly relates to a 4- (1, 2, 4-oxadiazole-5-yl) phenyl) formamide derivative and application thereof in preparation of medicines for preventing or treating arthritis.
Background
Inflammation is a common pathological process in the body caused by various injurious factors, and is mediated by a variety of inflammatory mediators, mainly including Prostanoids (PGs) and Leukotrienes (LTs). Immunization is a specific physiological reaction of the body contacting with antigenic foreign matters or different components, and the effect of the immune is to identify and remove the antigenic foreign matters so as to maintain the physiological balance of the body. Both immune and inflammatory responses are protective defensive responses of the body, however excessive immunity and inflammation are harmful to the human body. Immunization and inflammation are two different reactions of the body to foreign bodies, but are essential in that, immunization and inflammation are two sides of a problem, which are overlapped with each other and are inseparable. The most widely used anti-inflammatory immune drugs in clinic are non-steroidal anti-inflammatory drugs (NSAIDs) and steroidal anti-inflammatory drugs, but the anti-inflammatory drugs have serious adverse reactions while achieving good anti-inflammatory effects, so people pay more attention, and how to reduce the adverse reactions or find alternative drugs is one of the most important research tasks of pharmacy.
Arthritis is one of many autoimmune diseases, and the presence of autoantibodies triggers immune cells to release inflammatory molecules, causing damage to the joints and other organ systems. Current anti-cytokine therapies, such as tumor necrosis factor (TNF- α), interleukin (IL-1 β), have been used in the treatment of autoimmune diseases. Therefore, in the process of designing and developing new drugs, compounds with anti-arthritis potential can be screened according to whether the drug activity can inhibit the release of inflammatory factors NO, IL-1 beta and TNF-alpha. And the combination of the analysis of the compound on the treatment conditions of the adjuvant-induced arthritis model and other researches can provide an experimental basis for the treatment development of arthritis in the field of medicine and pharmacology.
Disclosure of Invention
In order to solve the technical problems, one of the purposes of the invention is to provide a (4- (1, 2, 4-oxadiazole-5-yl) phenyl) formamide derivative, which adopts the following technical scheme: a (4- (1, 2, 4-oxadiazol-5-yl) phenyl) carboxamide derivative, designated as f9, having the formula a:
the preparation route of the (4- (1, 2, 4-oxadiazol-5-yl) phenyl) carboxamide derivative f9 is as follows:
the route of preparation is mainly for the purpose of illustrating the invention and is not intended to be limiting in any way.
i. According to the reported method, 2-chloro-4-cyanopyridine and various anilines are subjected to nucleophilic substitution reaction, and the crude product is purified by column chromatography to obtain a compound a;
compound a and hydroxylamine hydrochloride in K 2 CO 3 Reacting under the action of a catalyst to generate a compound b;
reacting the compound b with 4-nitrobenzoyl chloride to obtain a compound c;
carrying out reduction reaction on the compound c to obtain an intermediate d;
v. substitution reaction of the compound d with chloroacetyl chloride to obtain a compound e;
dissolving the intermediate e in absolute ethyl alcohol, reacting with p-fluoroaniline (75 ℃), and purifying by column chromatography to obtain the (4- (1, 2, 4-oxadiazol-5-yl) phenyl) formamide derivative f9.
The second purpose of the invention is to provide the application of the (4- (1, 2, 4-oxadiazol-5-yl) phenyl) formamide derivative in preparing medicines for inhibiting nitric oxide NO production and/or tumor necrosis factor TNF-alpha production and/or interleukin IL-1 beta production.
Further, the medicine is any one of injection, tablet, pill, capsule, suspending agent or emulsion.
The invention also aims to provide the application of the (4- (1, 2, 4-oxadiazol-5-yl) phenyl) formamide derivative in medicines for treating arthritis.
Further, the arthritis is rheumatoid arthritis.
Further, the medicine is any one of injection, tablet, pill, capsule, suspending agent or emulsion.
The invention has the advantages that:
1. the experimental measurement result shows that the (4- (1, 2, 4-oxadiazol-5-yl) phenyl) formamide derivative f9 provided by the invention can well inhibit the secretion and release of NO, IL-1 beta and TNF-alpha by adding the (4- (1, 2, 4-oxadiazol-5-yl) phenyl) formamide derivative f9 into RAW264.7 cells induced by LPS.
2. Through in vivo experiments, (4- (1, 2, 4-oxadiazol-5-yl) phenyl) formamide derivative f9 can obviously treat arthritis rats induced by an adjuvant, and the (4- (1, 2, 4-oxadiazol-5-yl) phenyl) formamide derivative f9 has potential to develop into a medicament for treating arthritis diseases.
Drawings
FIG. 1 shows the effect of varying concentrations of (4- (1, 2, 4-oxadiazol-5-yl) phenyl) carboxamide derivative f9 on NO release after RAW264.7 cells are stimulated by LPS;
FIG. 2 effects of varying concentrations of (4- (1, 2, 4-oxadiazol-5-yl) phenyl) carboxamide derivative f9 on IL-1β and TNF- α release when RAW264.7 cells were stimulated with LPS;
FIG. 3 is a graph showing a comparison of right hind feet of rats in different groups in an adjuvant-induced arthritis model test;
FIG. 4 shows the change in swelling of the feet of rats in different groups in an adjuvant-induced arthritis model test, with time on the abscissa and foot volume on the ordinate;
FIG. 5 is a graph showing different groups of arthritis indices in an adjuvant-induced arthritis model test, with time on the abscissa and arthritis index on the ordinate;
FIG. 6 is a graph of changes in body weight of different groups of rats in an adjuvant-induced arthritis model test, with time on the abscissa;
FIG. 7 is a graph of IL-1β and TNF- α levels in rats of different groups in an adjuvant-induced arthritis model test, wherein FIG. 7A is IL-1β and FIG. 7B is TNF- α, and the abscissa of the graph is time.
Detailed Description
Unless otherwise indicated, terms used herein have meanings conventionally understood by those skilled in the art.
The following describes the technical scheme of the present invention in more detail with reference to examples:
example 1
Synthesis of (4- (1, 2, 4-oxadiazol-5-yl) phenyl) carboxamide derivative f 9:
compound e (294 mg,0.6 mM) was dissolved in 80mL of absolute ethanol, followed by the addition of p-fluoroaniline (889 mg,4.8 mM) and triethylamine (101 mg,1.2 mM) and refluxing at 75℃for 8h. TLC detects the progress of the reaction. After the reaction, the reaction solvent was removed. Purifying by column chromatography with ethyl acetate and petroleum ether (1:4) to obtain compound f9, wherein the compound f9 is white solid with a yield of 56%.
1 H NMR(500MHz,DMSO-d 6 )δ10.48(s,1H),9.67(s,1H),8.37(d,J＝5.3Hz,1H),8.14(d,J＝8.8Hz,2H),7.93(d,J＝8.8Hz,2H),7.86(d,J＝9.2Hz,2H),7.57(s,1H),7.35(dd,J＝5.2,1.4Hz,1H),7.30(d,J＝8.6Hz,2H),6.97(t,J＝8.9Hz,2H),6.63(dd,J＝9.0,4.5Hz,2H),6.03(t,J＝6.1Hz,1H),3.94(d,J＝5.8Hz,2H)； 13 C NMR(126MHz,DMSO)δ48.28,109.26,113.53,113.59,115.67,115.85,118.00,119.56,119.71,119.87,121.73,122.07,129.54,135.11,141.02,142.23,143.91,145.42,149.03,154.24,156.08,156.68,167.50,170.62,176.05。
HRMS(ESI)m/z[M+H] + :565.15666calcd for C 28 H 20 F 4 N 6 O 3 :565.15985。
Example 2
Anti-inflammatory Activity experiment of (4- (1, 2, 4-oxadiazol-5-yl) phenyl) carboxamide derivative f9
1) Experimental materials: (4- (1, 2, 4-oxadiazol-5-yl) phenyl) carboxamide derivative f9 (laboratory self-designed synthesis), NO detection kit (bi yun tian), RAW264.7 (university of medical science, anhui university, pharmaceutical college), ELASA kit (genealogy, wuhan), microplate reader (BIO-RAD), inverted biomicroscope (Chongqing optical instrumentation factory); reagent: cell culture medium, DMEM (high sugar) (GIBCO), fetal bovine serum (hjv), DMSO (Sigma).
2) Cell culture:
RAW264.7 macrophages used in the experiment are adherent growth cell lines, and are cultured by adopting DMEM culture solution containing 10% fetal calf serum. The culture environment is 37 ℃ and 5 percent CO 2 The incubator was replaced once a day, and cells in the logarithmic growth phase were taken and subjected to experiments.
3) Inhibition of NO release assay:
in the LPS-induced RAW264.7 cell model, the anti-inflammatory capacity of the compounds was assessed by their inhibition of NO release.
RAW264.7 cells were cultured in DMEM high-sugar medium supplemented with 10% fetal bovine serum, penicillin 100U/mL and streptomycin 100U/mL. RAW264.7 cells were plated at 6X 10 cells per well 4 After 24h incubation in 48-well plates, the old medium was discarded. The culture medium containing (4- (1, 2, 4-oxadiazol-5-yl) phenyl) carboxamide derivative f9 at various concentrations was then pre-treated for 1 hour and incubated with LPS at a concentration of 1. Mu.g/ml for 24 hours. 50 μl of the supernatant was placed in a 96-well plate, mixed with the same volume Griess assay agent, incubated at room temperature for 10 minutes, and absorbance was measured at 540nm using a multifunctional microplate reader. As a result, as shown in FIG. 1, it can be seen from FIG. 1 that as the amount of (4- (1, 2, 4-oxadiazol-5-yl) phenyl) carboxamide derivative f9 was increased from 0.78125. Mu.M to 12.5. Mu.M, the concentration of NO gradually decreased, indicating that (4- (1, 2, 4-oxadiazol-5-yl) phenyl) carboxamide derivative f9 inhibited LPS-induced release of NO (IC) in RAW264.7 cells in a dose-dependent manner 50 ＝1.981μM)。
4) Inhibition of TNF-alpha and IL-1 beta inflammatory factors
The potential anti-inflammatory capacity was further assessed by testing the inhibition of inflammatory factors TNF- α and IL-1β by (4- (1, 2, 4-oxadiazol-5-yl) phenyl) carboxamide derivative f9 in the LPS-induced RAW264.7 cell model.
RAW264.7 cells were plated at 6X 10 cells per well 4 After each incubation in 48-well plates for 24h, medium containing (4- (1, 2, 4-oxadiazol-5-yl) phenyl) carboxamide derivative f9 at different concentrations was added. 30. Mu.L of LPS (1. Mu.g/mL) was added after 1 hour and incubated for 24 hours. The supernatant was then aspirated and assayed according to ELASA kit protocol. As a result, as shown in FIG. 2, it can be seen from FIG. 2 that (4- (1, 2, 4-oxadiazol-5-yl) phenyl) carboxamide derivative f9 is capable of inhibiting the release of IL-1β and TNF- α inflammatory factors and inhibiting the release of IL-1β (IC) 50 Inhibition greater than TNF- α (IC) =5.94±0.35 μm 50 ＝10.23±1.04μM)。
Example 3
Adjuvant-induced arthritis model test
Experimental materials: sprague-Dawley female rats weighing 160-180g purchased from the university of Anhui university of Chinese medicine animal experiment center. The daily temperature, relative humidity and dark light cycle of the animal house are respectively kept at 23-25 ℃ and 40-60%.
2. Induction and experimental design of adjuvant arthritis
0.1mL of Freund's Complete Adjuvant (FCA) was injected intradermally into the left of the rat enough to cause inflammation. Normal rats were injected with an equal amount of physiological saline at the same site.
The rats were randomized into four groups 10 days after FCA injection. Two of these groups were drug groups to which (4- (1, 2, 4-oxadiazol-5-yl) phenyl) carboxamide derivative f9 (10 mg/kg and 30 mg/kg) was administered for 14 days, respectively, and the positive control group rats were administered indomethacin (10 mg/kg) for 14 days, and the other group was set as Model group to which physiological saline was administered daily.
The results are shown in FIGS. 3-6, with FIG. 3 being a comparison of the rat feet of the different treatment groups and FIG. 4 being a graph of the change in foot volume of the rats of the different groups. From fig. 3 and 4, it can be seen that the drug group reduced the swelling of the feet of rats in a concentration-dependent manner compared to the model group. Furthermore, as can be seen from FIG. 5, 30mg/kg of (4- (1, 2, 4-oxadiazol-5-yl) phenyl) carboxamide derivative f9 significantly reduced the arthritis index of the rats. Figure 6 shows that rats gain improved body weight after drug administration compared to the model group.
3. In vivo IL-1 beta and TNF-alpha level detection
After the rats were anesthetized, blood was collected from the heart artery. The blood sample was allowed to stand for 30 minutes and centrifuged at 3000r/min at 4℃for 10 minutes to collect serum. The levels of IL-1. Beta. And TNF-alpha. In serum were determined by ELISA. As a result, as shown in FIGS. 7A and 7B, it was found that (4- (1, 2, 4-oxadiazol-5-yl) phenyl) carboxamide derivative f9 reduced the levels of inflammatory factors IL-1. Beta. And TNF-. Alpha.in rat serum in a dose-dependent manner, as compared with the model group.
Experiments prove that the (4- (1, 2, 4-oxadiazole-5-yl) phenyl) formamide derivative f9 can inhibit the release and secretion of NO, IL-1 beta and TNF-alpha in cells, and obviously treat arthritis rats induced by an adjuvant, so that the (4- (1, 2, 4-oxadiazole-5-yl) phenyl) formamide derivative f9 provided by the invention has potential to develop into a medicament for treating arthritis diseases.
The above is merely a preferred practical example of the present invention, and is not intended to limit the invention; although the invention has been described in detail with reference to the foregoing embodiments, it will be understood by those of ordinary skill in the art that: any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (7)
1. A (4- (1, 2, 4-oxadiazol-5-yl) phenyl) carboxamide derivative is characterized by having a structural formula shown in formula (A):
2. use of a (4- (1, 2, 4-oxadiazol-5-yl) phenyl) carboxamide derivative according to claim 1 for the preparation of a medicament for the inhibition of nitric oxide production.
3. Use of a (4- (1, 2, 4-oxadiazol-5-yl) phenyl) carboxamide derivative according to claim 1 for the preparation of a medicament for the inhibition of TNF- α production.
4. Use of a (4- (1, 2, 4-oxadiazol-5-yl) phenyl) carboxamide derivative according to claim 1 for the preparation of a medicament for the inhibition of interleukin IL-1 beta production.
5. Use of a (4- (1, 2, 4-oxadiazol-5-yl) phenyl) carboxamide derivative according to claim 1 for the preparation of a medicament for the prophylaxis or treatment of arthritis.
6. The use according to claim 5, wherein the arthritis is rheumatoid arthritis.
7. The use according to claim 2 or 3 or 4 or 5, wherein the medicament is any one of an injection, a tablet, a pill, a capsule, a suspension or an emulsion.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110812039.3A CN113754646B (en) | 2021-07-19 | 2021-07-19 | (4- (1, 2, 4-oxadiazol-5-yl) phenyl) carboxamide derivatives and application thereof in anti-arthritis drugs |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110812039.3A CN113754646B (en) | 2021-07-19 | 2021-07-19 | (4- (1, 2, 4-oxadiazol-5-yl) phenyl) carboxamide derivatives and application thereof in anti-arthritis drugs |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN113754646A CN113754646A (en) | 2021-12-07 |
| CN113754646B true CN113754646B (en) | 2023-07-25 |
Family
ID=78787708
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202110812039.3A Active CN113754646B (en) | 2021-07-19 | 2021-07-19 | (4- (1, 2, 4-oxadiazol-5-yl) phenyl) carboxamide derivatives and application thereof in anti-arthritis drugs |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN113754646B (en) |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003087044A2 (en) * | 2002-04-09 | 2003-10-23 | 7Tm Pharma A/S | Novel carboxamide compounds for use in mch receptor related disorders |
| CN101495465A (en) * | 2006-05-30 | 2009-07-29 | 葛兰素集团有限公司 | 2-phenyl-5-amino-1,3,4-oxadiazoles and their use as nicotinic acetylcholine receptor ligands |
| CN101970420A (en) * | 2007-10-04 | 2011-02-09 | 默克雪兰诺有限公司 | Oxadiazole derivatives |
| EP2853532A1 (en) * | 2013-09-28 | 2015-04-01 | Instytut Farmakologii Polskiej Akademii Nauk | 1,2,4-oxadiazole derivatives as allosteric modulators of metabotropic glutamate receptors belonging to group III |
| CN111362930A (en) * | 2020-04-15 | 2020-07-03 | 安徽医科大学 | 1, 2, 4-oxadiazole-pyridine compound and application thereof |
| CN112716950A (en) * | 2020-12-29 | 2021-04-30 | 安徽医科大学 | New application of N- (2-phenylethyl) -5-phenyl-pyridine-2-formamide and medicine thereof |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20070038236A (en) * | 2005-10-05 | 2007-04-10 | 일동제약주식회사 | A novel oxazolidinone formamide derivative and manufacturing process thereof |
| CN101164538B (en) * | 2006-10-16 | 2011-12-14 | 中国医学科学院基础医学研究所 | Application of carboxyamido-triazoles compound and its salt in preparing medicine for treating painful diseases and/or inflammatory diseases |
| WO2014031928A2 (en) * | 2012-08-24 | 2014-02-27 | Philip Jones | Heterocyclic modulators of hif activity for treatment of disease |
-
2021
- 2021-07-19 CN CN202110812039.3A patent/CN113754646B/en active Active
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003087044A2 (en) * | 2002-04-09 | 2003-10-23 | 7Tm Pharma A/S | Novel carboxamide compounds for use in mch receptor related disorders |
| CN101495465A (en) * | 2006-05-30 | 2009-07-29 | 葛兰素集团有限公司 | 2-phenyl-5-amino-1,3,4-oxadiazoles and their use as nicotinic acetylcholine receptor ligands |
| CN101970420A (en) * | 2007-10-04 | 2011-02-09 | 默克雪兰诺有限公司 | Oxadiazole derivatives |
| EP2853532A1 (en) * | 2013-09-28 | 2015-04-01 | Instytut Farmakologii Polskiej Akademii Nauk | 1,2,4-oxadiazole derivatives as allosteric modulators of metabotropic glutamate receptors belonging to group III |
| CN111362930A (en) * | 2020-04-15 | 2020-07-03 | 安徽医科大学 | 1, 2, 4-oxadiazole-pyridine compound and application thereof |
| CN112716950A (en) * | 2020-12-29 | 2021-04-30 | 安徽医科大学 | New application of N- (2-phenylethyl) -5-phenyl-pyridine-2-formamide and medicine thereof |
Non-Patent Citations (1)
| Title |
|---|
| 3-(5-取代苯基-[1,3,4]恶二唑-2-亚甲硫基)-5-吡啶-3-基-[1,2,4]三唑-4-胺的合成及抗菌活性;胡国强,谢松强,许秋菊,黄文龙,张惠斌,黄胜堂;药学学报(04);第337-339页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN113754646A (en) | 2021-12-07 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN106905313B (en) | Nitric oxide donator type protoberberine analog derivative and its preparation method and application | |
| WO2022257995A1 (en) | Cryptotanshinone derivative and preparation method therefor and application thereof in lowering lipid and resisting obesity | |
| CN113754646B (en) | (4- (1, 2, 4-oxadiazol-5-yl) phenyl) carboxamide derivatives and application thereof in anti-arthritis drugs | |
| CN108853084A (en) | Quercetin is inhibiting the application in the aggregation of Tau abnormal protein | |
| CN101375850A (en) | Application of norisoboldine in preparing medicament for treating autoimmune disease | |
| Shi et al. | Modified Simiaowan prevents articular cartilage injury in experimental gouty arthritis by negative regulation of STAT3 pathway | |
| CN103524318A (en) | Application of allyl-containing monocarbonyl curcumin analogs in preparing antiinflammatory drugs | |
| CN106749228B (en) | A kind of jamaicin drug and the preparation method and application thereof | |
| LU101523B1 (en) | Application of taraxasterone in a preparation of medicament for preventing and treating senile dementia | |
| CN100546576C (en) | The application of hesperetin derivant in preparation anti inflammatory immunity medicine | |
| CN104224796B (en) | Application of oleanane triterpene ester derivative in preparation for anti-neurodegeneration medicine | |
| CN109172577B (en) | Application of burreed tuber component C in rhizoma sparganii in preparation of anti-blood stasis medicine | |
| CN112675221A (en) | Application of long pepper total alkaloids and piperine in preparation of adjuvant therapy medicines for Parkinson's disease | |
| CN112250624A (en) | Nicotinic acid derivative VII with anti-inflammatory, anti-platelet aggregation and immunosuppressive activities and application thereof | |
| Zhang et al. | Effects of Floium ginkgo extract and tertram ethypyrazine sodium chloride injection on expression of inflammatory cytokines and cerebral infarction | |
| Cai‑hong et al. | The latest research progress of novel coronavirus" Omicron sub‑variant BA. 5". | |
| CN113264826B (en) | Chain sesquiterpene compound and application thereof in preparation of drugs for preventing or treating inflammatory bowel diseases | |
| CN112294819B (en) | Inflammatory corpuscle inhibitor and application thereof | |
| CN117180243B (en) | Use of carnosone in preparing medicine for preventing and/or treating Alzheimer disease | |
| CN103421003A (en) | Coptisine derivatives with lipid regulation and hypoglycemic functions | |
| CN117137902B (en) | Application of (-) -equitable edible phenol in preparing medicine for preventing and/or treating Alzheimer disease | |
| CN105395808A (en) | Synergistic medicine composition for treating diabetes | |
| CN108904502B (en) | Application of burreed tuber component B in rhizoma sparganii in preparation of anti-blood stasis medicine | |
| CN113171366A (en) | Application of 3- (o-trifluoromethoxybenzenesulfonylamide) rutaecarpine in preparation of drug for preventing and treating alcoholic liver injury | |
| CN116768871A (en) | Puerarin derivative 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 |