CN110317232B - Preparation method and application of amide multi-active compound - Google Patents
Preparation method and application of amide multi-active compound Download PDFInfo
- Publication number
- CN110317232B CN110317232B CN201910165223.6A CN201910165223A CN110317232B CN 110317232 B CN110317232 B CN 110317232B CN 201910165223 A CN201910165223 A CN 201910165223A CN 110317232 B CN110317232 B CN 110317232B
- Authority
- CN
- China
- Prior art keywords
- nickel
- ligand
- methanol
- preparation
- compound
- 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
- 150000001875 compounds Chemical class 0.000 title claims abstract description 39
- 238000002360 preparation method Methods 0.000 title claims abstract description 12
- 150000001408 amides Chemical class 0.000 title claims abstract description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims abstract description 72
- 239000003446 ligand Substances 0.000 claims abstract description 40
- YIKSCQDJHCMVMK-UHFFFAOYSA-N Oxamide Chemical compound NC(=O)C(N)=O YIKSCQDJHCMVMK-UHFFFAOYSA-N 0.000 claims abstract description 21
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims abstract description 15
- 229910052802 copper Inorganic materials 0.000 claims abstract description 15
- 239000010949 copper Substances 0.000 claims abstract description 15
- 239000000243 solution Substances 0.000 claims abstract description 13
- 239000013078 crystal Substances 0.000 claims abstract description 9
- 239000003814 drug Substances 0.000 claims abstract description 9
- 150000002815 nickel Chemical class 0.000 claims abstract description 9
- 239000000706 filtrate Substances 0.000 claims abstract description 6
- 238000001914 filtration Methods 0.000 claims abstract description 6
- 239000011259 mixed solution Substances 0.000 claims abstract description 6
- 238000010992 reflux Methods 0.000 claims abstract description 6
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 claims abstract description 5
- ZLQBNKOPBDZKDP-UHFFFAOYSA-L nickel(2+);diperchlorate Chemical compound [Ni+2].[O-]Cl(=O)(=O)=O.[O-]Cl(=O)(=O)=O ZLQBNKOPBDZKDP-UHFFFAOYSA-L 0.000 claims abstract description 5
- 201000008968 osteosarcoma Diseases 0.000 claims description 6
- 238000000034 method Methods 0.000 claims description 4
- 230000002218 hypoglycaemic effect Effects 0.000 claims 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 abstract description 12
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 abstract description 12
- 229910052794 bromium Inorganic materials 0.000 abstract description 12
- 229910000570 Cupronickel Inorganic materials 0.000 abstract description 11
- YOCUPQPZWBBYIX-UHFFFAOYSA-N copper nickel Chemical compound [Ni].[Cu] YOCUPQPZWBBYIX-UHFFFAOYSA-N 0.000 abstract description 11
- 230000000694 effects Effects 0.000 abstract description 8
- 239000002246 antineoplastic agent Substances 0.000 abstract description 7
- 229940041181 antineoplastic drug Drugs 0.000 abstract description 7
- 229910021586 Nickel(II) chloride Inorganic materials 0.000 abstract description 4
- 230000001093 anti-cancer Effects 0.000 abstract description 4
- QMMRZOWCJAIUJA-UHFFFAOYSA-L nickel dichloride Chemical compound Cl[Ni]Cl QMMRZOWCJAIUJA-UHFFFAOYSA-L 0.000 abstract description 4
- 229940079593 drug Drugs 0.000 abstract description 3
- 239000008280 blood Substances 0.000 abstract description 2
- 210000004369 blood Anatomy 0.000 abstract description 2
- UQPSGBZICXWIAG-UHFFFAOYSA-L nickel(2+);dibromide;trihydrate Chemical compound O.O.O.Br[Ni]Br UQPSGBZICXWIAG-UHFFFAOYSA-L 0.000 abstract description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 abstract 2
- 229910052697 platinum Inorganic materials 0.000 abstract 1
- 210000004027 cell Anatomy 0.000 description 13
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 6
- 102000002072 Non-Receptor Type 1 Protein Tyrosine Phosphatase Human genes 0.000 description 6
- 108010015847 Non-Receptor Type 1 Protein Tyrosine Phosphatase Proteins 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 238000000338 in vitro Methods 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 239000003472 antidiabetic agent Substances 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical compound N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 description 3
- 229910052759 nickel Inorganic materials 0.000 description 3
- BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 3
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 229910021585 Nickel(II) bromide Inorganic materials 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 238000000921 elemental analysis Methods 0.000 description 2
- IPLJNQFXJUCRNH-UHFFFAOYSA-L nickel(2+);dibromide Chemical compound [Ni+2].[Br-].[Br-] IPLJNQFXJUCRNH-UHFFFAOYSA-L 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- IHIXIJGXTJIKRB-UHFFFAOYSA-N trisodium vanadate Chemical compound [Na+].[Na+].[Na+].[O-][V]([O-])([O-])=O IHIXIJGXTJIKRB-UHFFFAOYSA-N 0.000 description 2
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- XZKIHKMTEMTJQX-UHFFFAOYSA-N 4-Nitrophenyl Phosphate Chemical compound OP(O)(=O)OC1=CC=C([N+]([O-])=O)C=C1 XZKIHKMTEMTJQX-UHFFFAOYSA-N 0.000 description 1
- CGZZNTNFZCJQRE-UHFFFAOYSA-N Br.NC(=O)C(=O)N Chemical compound Br.NC(=O)C(=O)N CGZZNTNFZCJQRE-UHFFFAOYSA-N 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 101710088194 Dehydrogenase Proteins 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 102000002727 Protein Tyrosine Phosphatase Human genes 0.000 description 1
- 235000005811 Viola adunca Nutrition 0.000 description 1
- 240000009038 Viola odorata Species 0.000 description 1
- 235000013487 Viola odorata Nutrition 0.000 description 1
- 235000002254 Viola papilionacea Nutrition 0.000 description 1
- XJLXINKUBYWONI-DQQFMEOOSA-N [[(2r,3r,4r,5r)-5-(6-aminopurin-9-yl)-3-hydroxy-4-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2s,3r,4s,5s)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate Chemical compound NC(=O)C1=CC=C[N+]([C@@H]2[C@H]([C@@H](O)[C@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](OP(O)(O)=O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 XJLXINKUBYWONI-DQQFMEOOSA-N 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 229940127003 anti-diabetic drug Drugs 0.000 description 1
- 230000003178 anti-diabetic effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical class N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
- 229960004316 cisplatin Drugs 0.000 description 1
- 238000002447 crystallographic data Methods 0.000 description 1
- 231100000263 cytotoxicity test Toxicity 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 208000016097 disease of metabolism Diseases 0.000 description 1
- KAKKHKRHCKCAGH-UHFFFAOYSA-L disodium;(4-nitrophenyl) phosphate;hexahydrate Chemical compound O.O.O.O.O.O.[Na+].[Na+].[O-][N+](=O)C1=CC=C(OP([O-])([O-])=O)C=C1 KAKKHKRHCKCAGH-UHFFFAOYSA-L 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 230000005389 magnetism Effects 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 210000003470 mitochondria Anatomy 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- -1 oxamide copper-nickel Chemical compound 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 239000003801 protein tyrosine phosphatase 1B inhibitor Substances 0.000 description 1
- 108020000494 protein-tyrosine phosphatase Proteins 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000003259 recombinant expression Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 235000017550 sodium carbonate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 238000012916 structural analysis Methods 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- 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
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F15/00—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table
- C07F15/04—Nickel compounds
- C07F15/045—Nickel compounds without a metal-carbon linkage
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Diabetes (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses an amide multi-active compound and a preparation method and application thereof, the structural formula is as follows,
Description
Technical Field
The invention relates to a preparation method of an amide multi-active compound, and application of the compound in preparing an anti-cancer medicament and an anti-diabetic medicament.
Background
Since the discovery of cisplatin, transition metal complexes with targeting functions to proteins and DNA have attracted attention in the field of anticancer drugs, among many bridged ligands, oxamide bridged ligand is regarded as a multifunctional ligand, and has been paid attention to scientists by its unique bridged structure and its complex unique properties, however, the research on oxamide coordination compounds has been mostly focused on the fields of catalysis and molecular magnetism, and in recent years, more researchers have applied the oxamide coordination compounds to the research on anticancer drugs.
Type II diabetes, an endocrine-disturbance metabolic disease, has become a third most serious chronic disease threatening human health after tumor and cardiovascular disease. In the existing research on hypoglycemic drugs, many reports are made on PTP1B inhibitors, but no report is made on the research on the PTP1B inhibitory activity of the compounds.
Disclosure of Invention
Aiming at the prior art, the invention provides a novel oxamide ligand copper-nickel bimetallic complex compound containing bromine atoms, and provides a preparation method and application of the compound.
In order to achieve the purpose, the invention adopts the following technical scheme:
a bromine-containing oxamide ligand copper-nickel bimetallic complex compound has a structural formula as follows:
a preparation method of a bromine-containing oxamide ligand copper-nickel bimetallic coordination compound comprises the following steps:
dissolving 2.0-4.0mmol of oxamide mononuclear copper ligand in 10-20ml of methanol, dissolving 2.0-4.0mmol of nickel salt in 5-10ml of methanol, adding the dissolved nickel salt into the methanol solution of the mononuclear copper ligand, reacting for 1-5 hours at the temperature of 60-120 ℃, then adding the methanol solution dissolved with 4.0-8.0mmol of 1, 10-phenanthroline ligand into the mixed solution of the ligand, refluxing for 5-10 hours at the temperature of 60-100 ℃, filtering, and slowly volatilizing the filtrate for 1 week to obtain blue blocky crystals. Namely the bromine-containing oxamide ligand copper-nickel bimetallic coordination compound, wherein the nickel salt is as follows: nickel perchlorate, nickel chloride, nickel bromide, and the like.
The reaction equation is as follows:
the bromide oxamide ligand copper and nickel-containing bimetallic coordination compound is applied to the preparation of a medicament for treating human osteosarcoma cell SAOS-2.
The invention has the beneficial effects that: the bromine-containing oxamide ligand copper and nickel bimetallic complex compound has the molecular formula of C41H41BrClCuN7NiO10(ii) a Has molecular weight of 1029.42, has high anticancer activity, and can be used as raw material for preparing medicine for treating SAOS-2 of human osteosarcoma cell.
In addition, the compounds are found to have higher activity of reducing blood sugar for the first time. Compared with the currently commonly used similar medicines, the bromine-containing oxamide ligand copper and nickel bimetallic coordination compound has the characteristics of high activity, low cost, simple preparation method and the like, and provides a new way for developing related medicines.
Detailed Description
The present invention will be further illustrated by the following examples, which are intended to be merely illustrative and not limitative.
Example 1:
dissolving 2mmol of oxamide mononuclear copper ligand in 10ml of methanol, dissolving 2mmol of nickel perchlorate in 5ml of methanol, adding the dissolved nickel perchlorate into a methanol solution of the mononuclear copper ligand, reacting for 1 hour at 60 ℃, then adding the methanol solution dissolved with 4mmol of 1, 10-phenanthroline ligand into a mixed solution of the ligand, refluxing for 5 hours at 60 ℃, filtering, and slowly volatilizing the filtrate for 1 week to obtain a blue blocky crystal. Namely the bromine-containing oxamide ligand copper-nickel bimetallic coordination compound.
Infrared, elemental analysis and X-ray single crystal diffraction results:
infrared spectrum (KBr, cm-1) v (N-H)3417 v as (C ═ O) 161415751517; v iss(C6H6-H) 1452 725
Elemental analysis: c, 47.84; h, 4.01; n, 9.52%. Found C, 47.82; h, 4.03; n, 9.53 percent.
X-ray single crystal diffraction results:
molecular structure of bromine-containing oxamide ligand copper-nickel bimetallic coordination compound (ellipsoid probability 50%)
Crystallographic data and structural analysis parameters of compounds
Example 2:
dissolving 3mmol of oxamide mononuclear copper ligand in 20ml of methanol, dissolving 4mmol of nickel chloride in 10ml of methanol, adding the dissolved nickel chloride into a methanol solution of the mononuclear copper ligand, reacting for 3 hours at 80 ℃, then adding a methanol solution dissolved with 5mmol of 1, 10-phenanthroline ligand into a mixed solution of the ligand, refluxing for 8 hours at 90 ℃, filtering, and slowly volatilizing the filtrate for 1 week to obtain a blue blocky crystal. Namely the bromine-containing oxamide ligand copper-nickel bimetallic coordination compound.
Example 3:
dissolving 4mmol of oxamide mononuclear copper ligand in 20ml of methanol, dissolving 4mmol of nickel bromide in 10ml of methanol, adding the dissolved nickel bromide into a methanol solution of the mononuclear copper ligand, reacting for 5 hours at 100 ℃, then adding the methanol solution dissolved with 8mmol of 1 and 10-phenanthroline ligand into a mixed solution of the ligand, refluxing for 10 hours at 100 ℃, filtering, and slowly volatilizing the filtrate for 1 week to obtain a blue blocky crystal. Namely the bromine-containing oxamide ligand copper-nickel bimetallic coordination compound.
Test example:
the determination of the in vitro anti-cancer activity of the bromine-containing oxamide ligand copper-nickel bimetallic coordination compound is realized by an MTT experimental method, and the principle is as follows: based on the metabolic reduction of exogenous MTT (3- (4, 5-dimethylthiozol-2-yl) -2, 5-diphenylterazolium bromide), NADP-related dehydrogenase was present in mitochondria of living cells, yellow MTT was reduced to insoluble blue-violet Formazan (Formazan), dead cells were not treated with this enzyme, MTT was not reduced, Formazan was dissolved in DMSO, and then the optical density at a characteristic wavelength (570nm wavelength) was measured with a microplate reader to process the data. The method can indirectly reflect the number of living cells. Within a certain range of cell number, MTT crystals are formed in an amount proportional to the cell number. The method is widely used for activity detection of some bioactive factors, large-scale screening of anti-tumor drugs, cytotoxicity test, tumor radiosensitivity determination and the like.
The results of analyzing the SAOS-2 of the human normal cells and the human osteogenic sarcoma cells by MTT analysis and determining the IC50 value are shown in the table 1, and the conclusion is that: as can be seen from the data in the table, the anticancer drug of the present invention does not affect the growth of normal cells, but has high in vitro activity on human osteosarcoma cell SAOS-2, and can be used as a candidate compound of anticancer drugs.
TABLE 1 in vitro Activity test data of Bromide ligand-containing copper-nickel bimetallic complex anticancer drugs
| Human osteosarcoma cell | |
| Sample IC50 | 9.4μM/mL |
| Cell line | SAOS-2 |
Application of bromine-containing oxamide copper-nickel heteronuclear compound in preparation of antidiabetic drugs
The compounds synthesized in the above examples were used as test compounds to test their inhibitory activity against protein tyrosine phosphatase 1B (PTP1B), and the specific test cases were as follows:
200. mu.L of the reaction system contained PTP1B (recombinant expression), buffer (25mM HEPES,50mM sodium chloride, 2.5mM EDTA, 0.1% BSA, pH 7.2) and the above compounds, while blank control (containing no enzyme and the above compounds) and negative control (containing no the above compounds) were set, reacted at 37 ℃ for 10min, protein tyrosine phosphatase substrate PNPP was added, reacted at 37 ℃ for 30min, 2M Na2CO3 was added to terminate the reaction, and OD was measured at 405 nm. The inhibition rate was calculated from the OD value, and ═ 1- (OD sample-OD blank)/(OD negative-OD blank) ] × 100%. During primary screening, double holes are arranged at single concentration of each sample, the IC50 value of the sample with the inhibition rate of more than 70 percent is determined, six concentrations are diluted by each sample in a gradient manner, and double holes are arranged at each concentration. IC50 was calculated from the inhibition using a 4Parameter Logistic Model in Xlfit software. The test results are shown in Table 2.
TABLE 2 data for the in vitro inhibitory Activity of the Compound PTP1B
| Sample IC50 | 3.11±0.46(μM) |
| Sodium orthovanadate | 6.79±0.64(μM) |
As can be seen from the activity results in Table 2, the compound of the present invention shows good inhibitory activity against protein tyrosine phosphatase 1B, has an effect significantly superior to that of positive control sodium orthovanadate, and can be used for preparing a medicament for treating diabetes.
Although the present invention has been described with reference to the specific embodiments, it is not intended to limit the scope of the present invention, and various modifications and variations can be made by those skilled in the art without inventive changes based on the technical solution of the present invention.
Claims (3)
1. An amide multi-active compound, which is characterized by the following structural formula:
2. the method for preparing amide-type multi-active compounds according to claim 1, comprising the steps of: dissolving oxamide mononuclear copper ligand in methanol, dissolving nickel salt in methanol, adding the dissolved nickel salt into a methanol solution of the mononuclear copper ligand, reacting for 1-5 hours at 60-100 ℃, then adding the methanol solution dissolved with 1, 10-phenanthroline ligand into the mixed solution, refluxing at 60-120 ℃, filtering, and slowly volatilizing the filtrate to obtain blue blocky crystals, namely the amide multi-active compound, wherein the nickel salt is nickel perchlorate.
3. The use of amide-based multi-active compounds according to claim 1 for the preparation of a medicament for the treatment of human osteosarcoma cell SAOS-2 and for the treatment of hypoglycemic activity.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910165223.6A CN110317232B (en) | 2019-03-05 | 2019-03-05 | Preparation method and application of amide multi-active compound |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910165223.6A CN110317232B (en) | 2019-03-05 | 2019-03-05 | Preparation method and application of amide multi-active compound |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN110317232A CN110317232A (en) | 2019-10-11 |
| CN110317232B true CN110317232B (en) | 2021-06-25 |
Family
ID=68112747
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910165223.6A Active CN110317232B (en) | 2019-03-05 | 2019-03-05 | Preparation method and application of amide multi-active compound |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN110317232B (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102286057A (en) * | 2011-07-07 | 2011-12-21 | 北华大学 | Oleanane-type triterpenoid compounds and preparation method and medicinal use thereof |
-
2019
- 2019-03-05 CN CN201910165223.6A patent/CN110317232B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102286057A (en) * | 2011-07-07 | 2011-12-21 | 北华大学 | Oleanane-type triterpenoid compounds and preparation method and medicinal use thereof |
Non-Patent Citations (2)
| Title |
|---|
| A novel Mn-Cu bimetallic complex for enhanced chemodynamic therapy with simultaneous glutathione depletion;Shuhua Cao等;《Chem. Commun.》;20191002;第55卷;第12956-12959页 * |
| 两类功能性化合物的合成、结构及生物活性研究;李法辉;《中国博士学位论文全文数据库工程科技Ⅰ辑》;20110715;B014-12页，特别是第100页第1段，表4-5，第103页第2段 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN110317232A (en) | 2019-10-11 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN105198921A (en) | 2-carbonyl-2-phenylacetic acid salicyloyl hydrazone dibutyltin complex as well as preparation method and application of 2-carbonyl-2-phenylacetic acid salicyloyl hydrazone dibutyltin complex | |
| CN105237563A (en) | 2-oxo propionic acid p-hydroxy benzoyl hydrazone bis(2,4-dichlorobenzyl) tin complex and preparation method and application thereof | |
| CN108912149B (en) | Copper compound with 2-acetyl-3-ethylpyrazine thiosemicarbazone as ligand and synthetic method and application thereof | |
| CN105384770A (en) | 2-oxo-propionic acid salicyloyl hydrazone and di(p-methylbenzyl)tin complex as well as preparation method and application of 2-oxo-propionic acid salicyloyl hydrazone and di(p-methylbenzyl)tin complex | |
| CN105541898A (en) | Benzoylhydrazone bis(p-methylbenzyl) tin 2-carbonyl-3-phenylpropionate complex, and preparation method and application thereof | |
| CN105601663A (en) | 2-carbonyl-2-phenyl acetic acid salicylyl hydrazone tindiphenyl complex, and preparation method and applications thereof | |
| CN104059092B (en) | Benzimidazole zinc complex and preparation method thereof | |
| CN110330534B (en) | Novel 2-phenylpyridine-platinum (IV) precursor anticancer complex and synthesis method and application thereof | |
| CN110317218B (en) | Preparation method and application of high-activity tetranuclear polymer | |
| CN110317232B (en) | Preparation method and application of amide multi-active compound | |
| M Ibrahim et al. | Synthesis, structural and antimicrobial studies of binary and ternary complexes of a new tridentate thiosemicarbazone | |
| CN110317234B (en) | Preparation method and application of isonuclear high-activity polymer containing flutolanil phenanthroline ligand | |
| CN103087325B (en) | Ferrocenyl-containing tricyclohexyltin coordination polymer, and preparation method and application thereof | |
| CN109776623A (en) | The preparation method and application of a kind of fluorine-containing oxamides with/heteronuclear compound | |
| Shakir et al. | Design, synthesis and theoretical analysis of functionalized dicarboxylate moieties based on organotin (IV) dinuclear complexes: crystal structure elucidation and biological studies | |
| CN105399764A (en) | 2-oxo-propionic acid benzoyl hydrazone dibenzyl tin complex as well as preparation method and application thereof | |
| Zhao et al. | Synthesis, structure and spectroscopic studies on DNA binding, BSA interaction of a nickel (II) complex containing L–methionine Schiff base and 1, 10-phenanthroline | |
| CN109796505B (en) | Preparation method and application of amide compound with antitumor activity | |
| CN109705158B (en) | Independent double-center Ag complex and preparation method and anticancer activity evaluation thereof | |
| CN111620913B (en) | Ruthenium complex with thiosemicarbazone as ligand and application thereof | |
| CN109776615B (en) | Preparation method and application of active oxamide phenanthroline compound | |
| CN111116616B (en) | Preparation method and application of Schiff base complex of zinc | |
| CN109734729B (en) | Preparation method and application of hexanuclear amide compound | |
| CN110317235B (en) | Preparation method and application of heteronuclear polymer containing bromobipyridine ligand | |
| CN105315311A (en) | Nickel complex containing 5-chlorine salicylaldehyde shrinking 4- chlorine o-aminophenol Schiff alkali and pyridine and preparation method and application of nickel complex |
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 | ||
| CB03 | Change of inventor or designer information |
Inventor after: Li Fahui Inventor after: Yang Hekai Inventor after: Song Weiguo Inventor after: Guo Shoudong Inventor after: Yang Zhenyong Inventor before: Li Fahui Inventor before: Song Weiguo Inventor before: Guo Shoudong Inventor before: Yang Zhenyong |
|
| CB03 | Change of inventor or designer information | ||
| CB02 | Change of applicant information |
Address after: Weifang Medical College, 7166 Baotong West Street, Weifang City, Shandong Province, 261053 Applicant after: WEIFANG MEDICAL University Applicant after: Shandong Daohe Pharmaceutical Co.,Ltd. Address before: Weifang Medical College, 7166 Baotong West Street, Weifang City, Shandong Province, 261053 Applicant before: WEIFANG MEDICAL University Applicant before: SHANDONG DOYE PHARMACEUTICAL TECHNOLOGY Co.,Ltd. |
|
| CB02 | Change of applicant information | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |