CN106336429B - A kind of ALPHA-ketobutyric acid is to toluyl hydrazone stannous phenide complex and its preparation method and application - Google Patents
A kind of ALPHA-ketobutyric acid is to toluyl hydrazone stannous phenide complex and its preparation method and application Download PDFInfo
- Publication number
- CN106336429B CN106336429B CN201610735144.0A CN201610735144A CN106336429B CN 106336429 B CN106336429 B CN 106336429B CN 201610735144 A CN201610735144 A CN 201610735144A CN 106336429 B CN106336429 B CN 106336429B
- Authority
- CN
- China
- Prior art keywords
- complex
- alpha
- toluyl
- ketobutyric acid
- stannous phenide
- 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
- -1 toluyl hydrazone Chemical class 0.000 title claims abstract description 65
- 238000002360 preparation method Methods 0.000 title claims abstract description 15
- TYEYBOSBBBHJIV-UHFFFAOYSA-N 2-oxobutanoic acid Chemical compound CCC(=O)C(O)=O TYEYBOSBBBHJIV-UHFFFAOYSA-N 0.000 title claims description 42
- 239000002246 antineoplastic agent Substances 0.000 claims abstract description 11
- 229940041181 antineoplastic drug Drugs 0.000 claims abstract description 11
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 3
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 claims description 36
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 13
- 239000002904 solvent Substances 0.000 claims description 13
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 12
- 206010006187 Breast cancer Diseases 0.000 claims description 11
- 208000026310 Breast neoplasm Diseases 0.000 claims description 11
- 239000013078 crystal Substances 0.000 claims description 11
- 201000007270 liver cancer Diseases 0.000 claims description 11
- 208000014018 liver neoplasm Diseases 0.000 claims description 11
- 229910021626 Tin(II) chloride Inorganic materials 0.000 claims description 10
- 235000010290 biphenyl Nutrition 0.000 claims description 10
- 239000004305 biphenyl Substances 0.000 claims description 10
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 10
- 235000011150 stannous chloride Nutrition 0.000 claims description 10
- 239000001119 stannous chloride Substances 0.000 claims description 10
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 9
- 239000002253 acid Substances 0.000 claims description 9
- OAKJQQAXSVQMHS-UHFFFAOYSA-N hydrazine Substances NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 9
- 150000007513 acids Chemical class 0.000 claims description 8
- 238000002425 crystallisation Methods 0.000 claims description 8
- 230000008025 crystallization Effects 0.000 claims description 8
- 229910052718 tin Inorganic materials 0.000 claims description 7
- 238000000902 119Sn nuclear magnetic resonance spectroscopy Methods 0.000 claims description 6
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 claims description 6
- 238000005160 1H NMR spectroscopy Methods 0.000 claims description 6
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 claims description 6
- 206010028980 Neoplasm Diseases 0.000 claims description 6
- 238000001816 cooling Methods 0.000 claims description 6
- 238000001914 filtration Methods 0.000 claims description 6
- 229910052757 nitrogen Inorganic materials 0.000 claims description 6
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical group [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 claims description 5
- 201000011510 cancer Diseases 0.000 claims description 5
- 238000002447 crystallographic data Methods 0.000 claims description 5
- 201000005296 lung carcinoma Diseases 0.000 claims description 5
- 238000006243 chemical reaction Methods 0.000 claims description 3
- 239000000126 substance Substances 0.000 claims description 3
- TXUICONDJPYNPY-UHFFFAOYSA-N (1,10,13-trimethyl-3-oxo-4,5,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-17-yl) heptanoate Chemical compound C1CC2CC(=O)C=C(C)C2(C)C2C1C1CCC(OC(=O)CCCCCC)C1(C)CC2 TXUICONDJPYNPY-UHFFFAOYSA-N 0.000 claims 1
- OTEKOJQFKOIXMU-UHFFFAOYSA-N 1,4-bis(trichloromethyl)benzene Chemical compound ClC(Cl)(Cl)C1=CC=C(C(Cl)(Cl)Cl)C=C1 OTEKOJQFKOIXMU-UHFFFAOYSA-N 0.000 claims 1
- GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 claims 1
- 230000005311 nuclear magnetism Effects 0.000 claims 1
- SEJXNPFTEXQNOU-UHFFFAOYSA-N 2-(oxomethylidene)butanoic acid Chemical compound CCC(=C=O)C(O)=O SEJXNPFTEXQNOU-UHFFFAOYSA-N 0.000 abstract 2
- 210000004027 cell Anatomy 0.000 description 39
- 230000001093 anti-cancer Effects 0.000 description 13
- 238000012360 testing method Methods 0.000 description 11
- 239000003814 drug Substances 0.000 description 10
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- 238000011160 research Methods 0.000 description 8
- 150000001875 compounds Chemical class 0.000 description 7
- 238000000921 elemental analysis Methods 0.000 description 6
- 208000010507 Adenocarcinoma of Lung Diseases 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 238000000338 in vitro Methods 0.000 description 5
- 230000002401 inhibitory effect Effects 0.000 description 5
- 239000003446 ligand Substances 0.000 description 5
- 238000000034 method Methods 0.000 description 5
- 206010009944 Colon cancer Diseases 0.000 description 4
- 208000029742 colonic neoplasm Diseases 0.000 description 4
- 201000005249 lung adenocarcinoma Diseases 0.000 description 4
- 201000005202 lung cancer Diseases 0.000 description 4
- 208000020816 lung neoplasm Diseases 0.000 description 4
- 239000002262 Schiff base Substances 0.000 description 3
- 150000004753 Schiff bases Chemical class 0.000 description 3
- 230000000259 anti-tumor effect Effects 0.000 description 3
- 238000013459 approach Methods 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 125000002524 organometallic group Chemical group 0.000 description 3
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 201000008275 breast carcinoma Diseases 0.000 description 2
- 208000032839 leukemia Diseases 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical compound N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 125000000962 organic group Chemical group 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 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 2
- 238000012216 screening Methods 0.000 description 2
- FTZIQBGFCYJWKA-UHFFFAOYSA-N 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium Chemical compound S1C(C)=C(C)N=C1[N+]1=NC(C=2C=CC=CC=2)=NN1C1=CC=CC=C1 FTZIQBGFCYJWKA-UHFFFAOYSA-N 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 229910020813 Sn-C Inorganic materials 0.000 description 1
- 229910018732 Sn—C Inorganic materials 0.000 description 1
- 102000019259 Succinate Dehydrogenase Human genes 0.000 description 1
- 108010012901 Succinate Dehydrogenase Proteins 0.000 description 1
- 229910021627 Tin(IV) chloride Inorganic materials 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 1
- YAYRGNWWLMLWJE-UHFFFAOYSA-L carboplatin Chemical compound O=C1O[Pt](N)(N)OC(=O)C11CCC1 YAYRGNWWLMLWJE-UHFFFAOYSA-L 0.000 description 1
- 229960004562 carboplatin Drugs 0.000 description 1
- 208000019065 cervical carcinoma Diseases 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000010668 complexation reaction Methods 0.000 description 1
- AYOHIQLKSOJJQH-UHFFFAOYSA-N dibutyltin Chemical compound CCCC[Sn]CCCC AYOHIQLKSOJJQH-UHFFFAOYSA-N 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 230000003511 endothelial effect Effects 0.000 description 1
- WDQNIWFZKXZFAY-UHFFFAOYSA-M fentin acetate Chemical compound CC([O-])=O.C1=CC=CC=C1[Sn+](C=1C=CC=CC=1)C1=CC=CC=C1 WDQNIWFZKXZFAY-UHFFFAOYSA-M 0.000 description 1
- NJVOZLGKTAPUTQ-UHFFFAOYSA-M fentin chloride Chemical compound C=1C=CC=CC=1[Sn](C=1C=CC=CC=1)(Cl)C1=CC=CC=C1 NJVOZLGKTAPUTQ-UHFFFAOYSA-M 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 210000004907 gland Anatomy 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 229940042795 hydrazides for tuberculosis treatment Drugs 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 208000003747 lymphoid leukemia Diseases 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 210000003470 mitochondria Anatomy 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 239000013110 organic ligand Substances 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Substances [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 1
- 239000011814 protection agent Substances 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 238000012916 structural analysis Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 150000003606 tin compounds Chemical class 0.000 description 1
- XOLBLPGZBRYERU-UHFFFAOYSA-N tin dioxide Chemical compound O=[Sn]=O XOLBLPGZBRYERU-UHFFFAOYSA-N 0.000 description 1
- 229910001887 tin oxide Inorganic materials 0.000 description 1
- CVNKFOIOZXAFBO-UHFFFAOYSA-J tin(4+);tetrahydroxide Chemical compound [OH-].[OH-].[OH-].[OH-].[Sn+4] CVNKFOIOZXAFBO-UHFFFAOYSA-J 0.000 description 1
- QHGNHLZPVBIIPX-UHFFFAOYSA-N tin(ii) oxide Chemical compound [Sn]=O QHGNHLZPVBIIPX-UHFFFAOYSA-N 0.000 description 1
- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 1
- 238000001942 tin-119 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
Classifications
-
- 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
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/22—Tin compounds
- C07F7/2284—Compounds with one or more Sn-N linkages
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a kind of 2 carbonyl butyric acid to toluyl hydrazone stannous phenide complex, is the complex of following structure formula (I), wherein R is phenyl.The invention also discloses preparation method of the 2 carbonyl butyric acid to toluyl hydrazone stannous phenide complex and the applications in preparing anticancer drug.
Description
Technical field
The present invention relates to a kind of ALPHA-ketobutyric acids to toluyl hydrazone stannous phenide complex and preparation method thereof, and
Application of the ALPHA-ketobutyric acid to toluyl hydrazone stannous phenide complex in preparing anticancer drug.
Background technology
Organotin is a kind of metallo-organic compound containing Sn-C keys.Researcher just notices before very early
The Anticancer Activity in vitro of organo-tin compound.The research of organotin (IV) antitumor activity of compound can trace back to nineteen twenty-nine.
1967, Kanisawa etc. thought that stannic chloride is invalid to the primary tumor of mouse and rat.But in 1972, Brown had found,
Pass through food or drug administration by injection, triphenyltin acetate Ph3SnOOCCH3It can inhibit the tumour growth of mouse, and triphenyltin chloride
Then cannot.Between 1972 ~ 1977 years, Dutch scholar has studied a large amount of organo-tin compound, but finds no further screening valence
The compound of value.They continue deeper into research, finally found that the tin compound of two organic groups coordination, such as tin-oxide
(R2SnO), tin hydroxide ［ SnR2(OH) X ］ etc. have antitumor activity, and find out that they all contain or hydrolyze and can generate tin oxygen
Key.1986, Crowe etc. was found that some organo-tin compounds have preferable active anticancer again, anti-about organotin from this
The active research of cancer becomes the another extremely active hot spot after cis-platinum.1989, American National anticancer research institute
(National Cancer Institute) has carried out antitumor activity screening to more than 2,000 kinds of organo-tin compounds, as a result table
Some bright organo-tin compounds have inhibiting effect to P388 lymphocytic leukemias.2002, Gielen et al. was to organic
The activity of tin carboxylate compound has done comprehensive summing up, and many organo-tin compounds are thought after research really has preferably in vitro
Active anticancer.
Studies have shown that the organic group connected on organic tin atom and the ligand for participating in being coordinated decide organo-tin compound
Bioactivity, select some itself have the active organic ligand of good biological in organotin tin atom be coordinated cause
The great interest of people.Acylhydrazone is a kind of Schiff compound made of being modified by hydrazide kind compound, they
It is condensed by aldehydes or ketones and hydrazides, there is the bond type similar with peptide bond in molecule, there is good bioactivity, stronger match
Capability and various coordination mode, and have a wide range of applications in medicine, pesticide, material and analytical reagent etc..Closely
Nian Lai, domestic and international many researchers compare it in terms of bioactivity in depth to be studied, and research finds acylhydrazone class
Compound has the various actives such as anticancer, sterilization, anti-inflammatory.Therefore, acylhydrazone class Schiff ligand is combined with organotin, it is intended to
The stronger noval chemical compound of bioactivity is obtained, the interested research direction of people is become.
Chinese patent CN 102718794A disclose a kind of double acylhydrazone class Schiff stannous phenide complexs and its are making
Standby Antilung gland cancer, colon cancer, leukaemia cell drug in application.
Chinese patent CN 101851251A disclose a kind of acylhydrazone class Schiff ligand dibutyl tin complex and its
Application in the drug for preparing treatment liver cancer, adenocarcinoma of lung, breast cancer, prostate cancer, colon cancer or early young grain leukaemia.
Document (Journal of Organometallic Chemistry, 2014,75:It 83-91) reports, organotin
Acylhydrazone class Schiff base complex is thin to human colon cancer cell (HCT-116), human lung adenocarcinoma cell (A549), human umblilical vein endothelial
Born of the same parents (HUVEC) have compared with strong biological activity, and are better than carboplatin.
Document (Journal of Organometallic Chemistry, 2013,724:It 23-31) reports, series has
Machine tin acylhydrazone class Schiff base complex, organo-tin compound and acylhydrazone class Schiff ligand are respectively to human lung adenocarcinoma cell
(A549), the inhibiting effect of the cancer cells such as human colon cancer cell (HCT-8), people in loop (hl-60).
Document (Bioorganic ＆ Medicinal Chemistry Letters, 2015,25: 4461- 4463)
Report, active anticancer of a variety of acylhydrazone class Schiff ligands to human liver cancer cell (HuH-7) and human lung adenocarcinoma cell (A549).
Document (Journal of Organometallic Chemistry, 2016,864:It 48-58) reports, two hydrocarbon
Base tin acylhydrazone class Schiff base complex is to human lung adenocarcinoma cell (A549), human cervical carcinoma cell (HeLa), human breast cancer cell
(MCF-7) inhibiting effect of cancer cells such as.
It is the experiment proved that the substance with active anticancer, present invention choosing based on acylhydrazone class Schiff organotin complex
It selects and toluyl hydrazine, 2- batanone acids is reacted under certain condition with diphenyl stannous chloride, synthesis has been obtained to human lung cancer
Cell (H460), human liver cancer cell (HepG2) and human breast cancer cell (MCF7) have the complex of certain inhibitory activity, to open
Hair anticancer drug provides new approach.
Invention content
There is provided a kind of ALPHA-ketobutyric acids to toluyl hydrazone stannous phenide complex for the first object of the present invention.
The second object of the present invention is to provide above-mentioned ALPHA-ketobutyric acid and is prepared to toluyl hydrazone stannous phenide complex
Method.
The third object of the present invention is to provide above-mentioned ALPHA-ketobutyric acid and is being made to toluyl hydrazone stannous phenide complex
Application in standby anticancer drug.
A kind of ALPHA-ketobutyric acid as the first aspect of the present invention is to toluyl hydrazone stannous phenide complex, for knot
The complex of structure formula (I)
(I)
Wherein R is phenyl.
The ALPHA-ketobutyric acid of the present invention is to toluyl hydrazone stannous phenide complex through elemental analysis, infrared spectrum, core
Magnetic resonance spectrum and X-ray single crystal diffraction structural analysis, it is as a result as follows：
Elemental analysis (C24H22N2O3Sn)：Calculated value：C 57.06, H 4.39, N 5.55；Measured value：C 57.10, H
4.41, N 5.55.
FT-IR (KBr, ν/cm-1): 3059, 3043, 2980, 2937, 2879, 1633, 1597, 1581,
1490, 1479, 1394, 1340, 1062, 844, 750, 732, 694, 626, 605, 586, 543, 487,
451。
1H NMR (500 MHz, CDCl3, δ/ppm): 8.23 (d, J =8.2 Hz, 2H), 7.81-7.83 (m,
4H), 7.45-7.48 (m, 6H), 7.32 (d, J =7.9 Hz, 2H), 3.49 (s, 3H), 3.08-3.13 (q,J =7.5 Hz, 2H), 2.46 (s, 3H), 1.30 (t, J =7.5 Hz, 3H)。
13C NMR (126 MHz, CDCl3, δ/ppm): 174.84, 163.45, 159.51, 143.66,
136.14, 135.73, 131.38, 129.44, 129.37, 129.24, 128.78, 21.81, 21.15, 10.71。
119Sn NMR (187 MHz, CDCl3, δ/ppm): -294.70。
The ALPHA-ketobutyric acid of the present invention is crystal structure to toluyl hydrazone stannous phenide complex, and crystal is monocline
Crystallographic system, space group P2 (1)/n, a=1.3093 (3) nm, b=0.89534 (17) nm, c=1.9338 (4) nm, α=
γ=90 °, β=100.208 (3) °, Z=4, V=2.2310 (7) nm3, the Mgm of Dc=1.504-3, m (MoK α)=
1.172 mm-1, F (000)=1016.
The ALPHA-ketobutyric acid of the present invention is structurally characterized in that toluyl hydrazone stannous phenide complex：Tin is former in molecule
Son is hexa-coordinate distorted octahedron configuration.
The ALPHA-ketobutyric acid of the present invention has certain thermostabilization range to toluyl hydrazone stannous phenide complex,
196 DEG C or less can be stabilized.
A kind of ALPHA-ketobutyric acid as the second aspect of the present invention is to the system of toluyl hydrazone stannous phenide complex
Diphenyl stannous chloride is added, to toluyl hydrazine, 2- batanone acids and molten in Preparation Method in the reaction vessel for having nitrogen protection
Agent absolute methanol reacts 5 ~ 24 h under conditions of temperature is 45 ~ 65 DEG C, cooling, and filtering controls under conditions of 20 ~ 35 DEG C
Solvent volatilization crystallization, obtains yellow transparent crystal, as ALPHA-ketobutyric acid is to toluyl hydrazone stannous phenide complex.
The present invention ALPHA-ketobutyric acid be to the preparation characteristic of toluyl hydrazone stannous phenide complex：From relatively easy
The raw material being easy to get sets out, and without the separation of intermediate, directly obtains complicated molecule, i.e. one kettle way；Such reaction exists
Economically with it is environmental-friendly on advantageously.
In a preferred embodiment of the invention, the diphenyl stannous chloride, to toluyl hydrazine, 2- batanone acids
The amount ratio of the substance of three is 1:(1~1.05):(1.05~1.15).
In a preferred embodiment of the invention, the solvent absolute methanol dosage is every mM of diphenyl dichloride
Tin adds 15 ~ 35 milliliters.
A kind of ALPHA-ketobutyric acid as the third aspect of the present invention is making toluyl hydrazone stannous phenide complex
Application in standby anticancer drug.
Applicant has carried out Anticancer Activity in vitro to above-mentioned ALPHA-ketobutyric acid to toluyl hydrazone stannous phenide complex
Determining research, it is thus identified that ALPHA-ketobutyric acid has certain anticancer bioactive to toluyl hydrazone stannous phenide complex,
That is the purposes of above-mentioned complex is the application in preparing anticancer drug, be exactly specifically prepare anti-human lung cancer,
Application in human liver cancer and human breast carcinoma drug.
The ALPHA-ketobutyric acid of the present invention is to toluyl hydrazone stannous phenide complex to human lung carcinoma cell, human liver cancer cell
Show that good active anticancer, ALPHA-ketobutyric acid of the invention match toluyl hydrazone stannous phenide with human breast cancer cell
The features such as object active anticancer is high, at low cost, preparation method is simple is closed, the anticancer drug to develop new provides new way.
Description of the drawings
Fig. 1 is IR spectrogram of the ALPHA-ketobutyric acid to toluyl hydrazone stannous phenide complex.
Fig. 2 is ALPHA-ketobutyric acid to toluyl hydrazone stannous phenide complex1H NMR spectras.
Fig. 3 is ALPHA-ketobutyric acid to toluyl hydrazone stannous phenide complex13C NMR spectras.
Fig. 4 is ALPHA-ketobutyric acid to toluyl hydrazone stannous phenide complex119Sn NMR spectras.
Fig. 5 is crystal structure figure of the ALPHA-ketobutyric acid to toluyl hydrazone stannous phenide complex.
Fig. 6 is TG-DTG curve of the ALPHA-ketobutyric acid to toluyl hydrazone stannous phenide complex.
Specific implementation mode
By detailed description below, invention is further described in detail.
Embodiment 1：
Preparation of the ALPHA-ketobutyric acid to toluyl hydrazone stannous phenide complex：
Be added in the 100mL three-necked flasks for having nitrogen protection 0.344g (1.0mmol) diphenyl stannous chloride,
0.150g (1.0mmol) to toluyl hydrazine, 0.112g (1.1mmol) 2- batanone acids and 15mL solvent absolute methanols,
Temperature reacts 8 h under conditions of being 45 ~ 65 DEG C, cooling, filtering, and solvent volatilization crystallization is controlled under conditions of 20 ~ 35 DEG C, is obtained yellow
Color transparent crystal, as ALPHA-ketobutyric acid are to toluyl hydrazone stannous phenide complex.Yield：80.9%.Fusing point：196~198
℃(dec)。
Elemental analysis (C24H22N2O3Sn)：Calculated value：C 57.06, H 4.39, N 5.55；Measured value：C 57.10, H
4.41, N 5.55.
FT-IR (KBr, ν/cm-1): 3059, 3043, 2980, 2937, 2879, 1633, 1597, 1581,
1490, 1479, 1394, 1340, 1062, 844, 750, 732, 694, 626, 605, 586, 543, 487,
451。
1H NMR (500 MHz, CDCl3, δ/ppm): 8.23 (d, J =8.2 Hz, 2H), 7.81-7.83 (m,
4H), 7.45-7.48 (m, 6H), 7.32 (d, J =7.9 Hz, 2H), 3.49 (s, 3H), 3.08-3.13 (q,J =7.5 Hz, 2H), 2.46 (s, 3H), 1.30 (t, J =7.5 Hz, 3H)。
13C NMR (126 MHz, CDCl3, δ/ppm): 174.84, 163.45, 159.51, 143.66,
136.14, 135.73, 131.38, 129.44, 129.37, 129.24, 128.78, 21.81, 21.15, 10.71。
119Sn NMR (187 MHz, CDCl3, δ/ppm): -294.70。
Crystallographic data：Monoclinic system, space group P2 (1)/n, a=1.3093 (3) nm, b=0.89534 (17)
Nm, c=1.9338 (4) nm, α=γ=90 °, β=100.208 (3) °, Z=4, V=2.2310 (7) nm3, Dc=
1.504 Mg·m-3, m (MoK α)=1.172 mm-1, F (000)=1016.
Embodiment 2：
Preparation of the ALPHA-ketobutyric acid to toluyl hydrazone stannous phenide complex：
Be added in the 100mL three-necked flasks for having nitrogen protection 0.344g (1.0mmol) diphenyl stannous chloride,
0.150g (1.0mmol) to toluyl hydrazine, 0.107g (1.05mmol) 2- batanone acids and 35mL solvent absolute methanols,
Temperature reacts 5 h under conditions of being 45 ~ 65 DEG C, cooling, filtering, and solvent volatilization crystallization is controlled under conditions of 20 ~ 35 DEG C, is obtained yellow
Color transparent crystal, as ALPHA-ketobutyric acid are to toluyl hydrazone stannous phenide complex.Yield：86.5%.Fusing point：196~198
℃(dec)。
Elemental analysis (C24H22N2O3Sn)：Calculated value：C 57.06, H 4.39, N 5.55；Measured value：C 57.10, H
4.41, N 5.55.
FT-IR (KBr, ν/cm-1): 3059, 3043, 2980, 2937, 2879, 1633, 1597, 1581,
1490, 1479, 1394, 1340, 1062, 844, 750, 732, 694, 626, 605, 586, 543, 487,
451。
1H NMR (500 MHz, CDCl3, δ/ppm): 8.23 (d, J =8.2 Hz, 2H), 7.81-7.83 (m,
4H), 7.45-7.48 (m, 6H), 7.32 (d, J =7.9 Hz, 2H), 3.49 (s, 3H), 3.08-3.13 (q,J =7.5 Hz, 2H), 2.46 (s, 3H), 1.30 (t, J =7.5 Hz, 3H)。
13C NMR (126 MHz, CDCl3, δ/ppm): 174.84, 163.45, 159.51, 143.66,
136.14, 135.73, 131.38, 129.44, 129.37, 129.24, 128.78, 21.81, 21.15, 10.71。
119Sn NMR (187 MHz, CDCl3, δ/ppm): -294.70。
Crystallographic data：Monoclinic system, space group P2 (1)/n, a=1.3093 (3) nm, b=0.89534 (17)
Nm, c=1.9338 (4) nm, α=γ=90 °, β=100.208 (3) °, Z=4, V=2.2310 (7) nm3, Dc=
1.504 Mg·m-3, m (MoK α)=1.172 mm-1, F (000)=1016.
Embodiment 3：
Preparation of the ALPHA-ketobutyric acid to toluyl hydrazone stannous phenide complex：
Be added in the 100mL three-necked flasks for having nitrogen protection 0.344g (1.0mmol) diphenyl stannous chloride,
0.157g (1.05mmol) to toluyl hydrazine, 0.117g (1.15mmol) 2- batanone acids and 25mL solvent absolute methanols,
24 h are reacted under conditions of temperature is 45 ~ 65 DEG C, cooling, filtering controls solvent volatilization crystallization under conditions of 20 ~ 35 DEG C,
Yellow transparent crystal is obtained, as ALPHA-ketobutyric acid is to toluyl hydrazone stannous phenide complex.Yield：84.6%.Fusing point：196
~198℃(dec)。
Elemental analysis (C24H22N2O3Sn)：Calculated value：C 57.06, H 4.39, N 5.55；Measured value：C 57.10, H
4.41, N 5.55.
FT-IR (KBr, ν/cm-1): 3059, 3043, 2980, 2937, 2879, 1633, 1597, 1581,
1490, 1479, 1394, 1340, 1062, 844, 750, 732, 694, 626, 605, 586, 543, 487,
451。
1H NMR (500 MHz, CDCl3, δ/ppm): 8.23 (d, J =8.2 Hz, 2H), 7.81-7.83 (m,
4H), 7.45-7.48 (m, 6H), 7.32 (d, J =7.9 Hz, 2H), 3.49 (s, 3H), 3.08-3.13 (q,J =7.5 Hz, 2H), 2.46 (s, 3H), 1.30 (t, J =7.5 Hz, 3H)。
13C NMR (126 MHz, CDCl3, δ/ppm): 174.84, 163.45, 159.51, 143.66,
136.14, 135.73, 131.38, 129.44, 129.37, 129.24, 128.78, 21.81, 21.15, 10.71。
119Sn NMR (187 MHz, CDCl3, δ/ppm): -294.70。
Crystallographic data：Monoclinic system, space group P2 (1)/n, a=1.3093 (3) nm, b=0.89534 (17)
Nm, c=1.9338 (4) nm, α=γ=90 °, β=100.208 (3) °, Z=4, V=2.2310 (7) nm3, Dc=
1.504 Mg·m-3, m (MoK α)=1.172 mm-1, F (000)=1016.
Embodiment 4：
Preparation of the ALPHA-ketobutyric acid to toluyl hydrazone stannous phenide complex：
Be added in the 500mL three-necked flasks for having nitrogen protection 3.440g (10.0mmol) diphenyl stannous chloride,
1.545g (10.3mmol) to toluyl hydrazine, 1.122g (11.0mmol) 2- batanone acids and 200mL solvent absolute methanols,
22 h are reacted under conditions of temperature is 45 ~ 65 DEG C, cooling, filtering controls solvent volatilization crystallization under conditions of 20 ~ 35 DEG C,
Yellow transparent crystal is obtained, as ALPHA-ketobutyric acid is to toluyl hydrazone stannous phenide complex.Yield：78.7%.Fusing point：196
~198℃(dec)。
Elemental analysis (C24H22N2O3Sn)：Calculated value：C 57.06, H 4.39, N 5.55；Measured value：C 57.10, H
4.41, N 5.55.
FT-IR (KBr, ν/cm-1): 3059, 3043, 2980, 2937, 2879, 1633, 1597, 1581,
1490, 1479, 1394, 1340, 1062, 844, 750, 732, 694, 626, 605, 586, 543, 487,
451。
1H NMR (500 MHz, CDCl3, δ/ppm): 8.23 (d, J =8.2 Hz, 2H), 7.81-7.83 (m,
4H), 7.45-7.48 (m, 6H), 7.32 (d, J =7.9 Hz, 2H), 3.49 (s, 3H), 3.08-3.13 (q,J =7.5 Hz, 2H), 2.46 (s, 3H), 1.30 (t, J =7.5 Hz, 3H)。
13C NMR (126 MHz, CDCl3, δ/ppm): 174.84, 163.45, 159.51, 143.66,
136.14, 135.73, 131.38, 129.44, 129.37, 129.24, 128.78, 21.81, 21.15, 10.71。
119Sn NMR (187 MHz, CDCl3, δ/ppm): -294.70。
Crystallographic data：Monoclinic system, space group P2 (1)/n, a=1.3093 (3) nm, b=0.89534 (17)
Nm, c=1.9338 (4) nm, α=γ=90 °, β=100.208 (3) °, Z=4, V=2.2310 (7) nm3, Dc=
1.504 Mg·m-3, m (MoK α)=1.172 mm-1, F (000)=1016.
Test example：
For the ALPHA-ketobutyric acid of the present invention to toluyl hydrazone stannous phenide complex, Anticancer Activity in vitro measurement is logical
Cross the realization of MTT experiment method.
MTT analytic approach：
3- (4,5-Dimethylthiazol-2-yl) -2,5-diphenyltetrazolium is restored with metabolism
Based on bromide.Succinate dehydrogenase in living cells mitochondria can make exogenous MTT be reduced to the bluish violet of water-insoluble
Crystallization first a ceremonial jade-ladle, used in libation (Formazan) is simultaneously deposited in cell, and dead cell is without this function.Dimethyl sulfoxide (DMSO) (DMSO) can dissolve cell
In first a ceremonial jade-ladle, used in libation, with microplate reader measure characteristic wavelength optical density, can reflect living cells quantity indirectly.
The ALPHA-ketobutyric acid of the preparation of embodiment 1 is measured to toluyl hydrazone stannous phenide complex pair using mtt assay
The inhibitory activity of human lung carcinoma cell (H460), human liver cancer cell (HepG2) and human breast cancer cell (MCF7).
Cell strain and cultivating system：H460, HepG2 and MCF7 cell strain are derived from American tissue incubator (ATCC).With containing
RPMI 1640 (GIBICO companies) culture medium of 10% fetal calf serum, in 5% (volume fraction) CO2, 37 DEG C of saturated humidity incubators
Interior carry out in vitro culture.
Test process：Test liquid (1nM ~ 10 μM) is added separately to according to the concentration gradient of concentration in each hole, often
A concentration sets 6 parallel holes.Experiment is divided into drug study group (the test medicine for being separately added into various concentration), control group (only plus is trained
Nutrient solution and cell are not added with test medicine) and blank group (only plus cultivating medicine, be not added with cell and test medicine).Orifice plate after dosing is set
In 37 DEG C, 5%CO272h is cultivated in incubator.The activity of control drug is measured according to the method for test sample.Cultivating 72h
In orifice plate afterwards, add 40 μ L of MTT (being made into 4mg/mL with D-Hanks buffer solutions) per hole.After placing 4h at 37 DEG C, upper layer is removed
Clear liquid.Add 150 μ L DMSO per hole, vibrate 5min, makes Formazan crystallization dissolvings.Finally, using automatic microplate reader in 570nm
The optical density in each hole is detected at wavelength.
Data processing：Data processing uses 7.0 programs of Graph Pad Prism version, complex IC50Pass through journey
The nonlinear regression model (NLRM) with S-shaped dose response is fitted to obtain in sequence.
It is thin to human lung carcinoma cell (H460), human liver cancer cell (HepG2) and human breast cancer cell (MCF7) with MTT analytic approach
Born of the same parents' strain is analyzed, its IC is measured50Value, the results are shown in Table 1, and conclusion is：From the data in the table, with the 2- carbonyls of the present invention
Butyric acid is used as anticancer drug to toluyl hydrazone stannous phenide complex, to human lung carcinoma cell (H460), human liver cancer cell
(HepG2) and human breast cancer cell (MCF7) has certain drug effect, can be used as the candidate compound of anticancer drug.
1 ALPHA-ketobutyric acid of table is to toluyl hydrazone stannous phenide complex anticancer drug external activity test data.
| Human lung cancer | Human liver cancer | Human breast carcinoma | |
| Cell strain | H460 | HepG2 | MCF7 |
| IC50(μM) | 1.65±0.27 | 1.81±0.21 | 1.20±0.12 |
ALPHA-ketobutyric acid prepared by remaining embodiment is to toluyl hydrazone stannous phenide complex with mtt assay to human lung cancer
The same test example of active anticancer test method of cell (H460), human liver cancer cell (HepG2) and human breast cancer cell (MCF7) is surveyed
Test result and table 1 are essentially identical.
It these are only the preferred embodiment of the present invention and test example, be not intended to restrict the invention, it is clear that the skill of this field
Art personnel can carry out the present invention various changes, modification without departing from the spirit and scope of the present invention.If to the present invention's
These modifications and variations within the scope of the claims of the present invention and its equivalent technology, belong to the protection model of the present invention
It encloses.
Claims (6)
- It is the complex of following structure formula (I) 1. a kind of ALPHA-ketobutyric acid is to toluyl hydrazone stannous phenide complex：(I)Wherein R is phenyl；The complex (I) is crystal structure, and crystallographic data is as follows：Monoclinic system, space group P2 (1)/n, a=1.3093 (3) nm, b=0.89534 (17) nm, c=1.9338 (4) nm, α=γ=90 °, β= 100.208 (3) °, Z=4, V=2.2310 (7) nm3, the Mgm of Dc=1.504-3, m (MoK α)=1.172 mm-1, F (000) = 1016；Tin atom is hexa-coordinate distorted octahedron configuration in molecule；The ir data of the complex (I)：FT-IR (KBr, ν/cm-1): 3059, 3043, 2980, 2937, 2879, 1633, 1597, 1581, 1490, 1479, 1394, 1340, 1062, 844, 750, 732, 694, 626, 605, 586, 543, 487, 451；Nuclear-magnetism composes number According to：1H NMR (500 MHz, CDCl3, δ/ppm): 8.23 (d, J =8.2 Hz, 2H), 7.81-7.83 (m, 4H), 7.45-7.48 (m, 6H), 7.32 (d, J =7.9 Hz, 2H), 3.49 (s, 3H), 3.08-3.13 (q, J = 7.5 Hz, 2H), 2.46 (s, 3H), 1.30 (t, J =7.5 Hz, 3H)；13C NMR (126 MHz, CDCl3, δ/ ppm): 174.84, 163.45, 159.51, 143.66, 136.14, 135.73, 131.38, 129.44, 129.37, 129.24, 128.78, 21.81, 21.15, 10.71；119Sn NMR (187 MHz, CDCl3, δ/ppm): - 294.70；The complex (I) can be stabilized at 196 DEG C or less.
- 2. ALPHA-ketobutyric acid described in claim 1 is to the preparation method of toluyl hydrazone stannous phenide complex, feature Be be added in the reaction vessel for having nitrogen protection diphenyl stannous chloride, to toluyl hydrazine, 2- batanone acids and solvent without Water methanol reacts 5 ~ 24 h under conditions of temperature is 45 ~ 65 DEG C, cooling, and filtering controls solvent under conditions of 20 ~ 35 DEG C Volatilization crystallization, obtains yellow transparent crystal, as ALPHA-ketobutyric acid is to toluyl hydrazone stannous phenide complex.
- 3. preparation method as claimed in claim 2, which is characterized in that the diphenyl stannous chloride, to toluyl hydrazine, The amount ratio of the substance of 2- batanone acid threes is 1:(1~1.05):(1.05~1.15).
- 4. preparation method as claimed in claim 2, which is characterized in that the solvent absolute methanol dosage is every mM of hexichol Base stannous chloride adds 15 ~ 35 milliliters.
- 5. ALPHA-ketobutyric acid described in claim 1 is to toluyl hydrazone stannous phenide complex answering in preparing anticancer drug With.
- 6. the application described in claim 5, wherein the cancer cell is human lung carcinoma cell, human liver cancer cell, human breast cancer cell.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610735144.0A CN106336429B (en) | 2016-08-28 | 2016-08-28 | A kind of ALPHA-ketobutyric acid is to toluyl hydrazone stannous phenide complex and its preparation method and application |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610735144.0A CN106336429B (en) | 2016-08-28 | 2016-08-28 | A kind of ALPHA-ketobutyric acid is to toluyl hydrazone stannous phenide complex and its preparation method and application |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN106336429A CN106336429A (en) | 2017-01-18 |
| CN106336429B true CN106336429B (en) | 2018-09-14 |
Family
ID=57822302
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610735144.0A Active CN106336429B (en) | 2016-08-28 | 2016-08-28 | A kind of ALPHA-ketobutyric acid is to toluyl hydrazone stannous phenide complex and its preparation method and application |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106336429B (en) |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105237563B (en) * | 2015-11-11 | 2018-01-16 | 衡阳师范学院 | A kind of 2 carbonyl propionic acid para hydroxybenzene formyl hydrazone two (2,4 dichloro benzyl) tin complexs and its preparation method and application |
| CN105348318A (en) * | 2015-11-11 | 2016-02-24 | 衡阳师范学院 | 2-carbonyl butyric acid benzoyl hydrazone dibenzyl tin complex, preparation method therefor and applications |
| CN105237562A (en) * | 2015-11-11 | 2016-01-13 | 衡阳师范学院 | 2-oxo propionic acid salicyloyl hydrazone tin diphenyl complex and preparation method and application thereof |
-
2016
- 2016-08-28 CN CN201610735144.0A patent/CN106336429B/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CN106336429A (en) | 2017-01-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN106432323A (en) | 2-carbonyl butyric acid p-methoxy benzoyl hydrazone di-n-butyltin complex and preparation method and application thereof | |
| CN106336427B (en) | A kind of 2- carbonyl -2- phenylacetic acid p-nitrophenyl formyl hydrazone two (2,4- dichloro benzyl) tin complex and its preparation method and application | |
| CN106336430B (en) | A kind of ALPHA-ketobutyric acid p-nitrophenyl formyl hydrazone di-n-butyl tin complex and its preparation method and application | |
| CN106220669B (en) | A kind of dialkyl tin complex of the ligand containing acylhydrazone and its preparation method and application | |
| CN106366113A (en) | 2-oxo-propionic acid p-toluyl hydrazone di-2, 4-dichlorobenzyltin complex and its preparation method and use | |
| CN106336429B (en) | A kind of ALPHA-ketobutyric acid is to toluyl hydrazone stannous phenide complex and its preparation method and application | |
| CN106279258B (en) | A kind of dialkyl tin complex and its preparation method and application | |
| CN106220674B (en) | A kind of Dibenzyltin complex and its preparation method and application | |
| CN106279261B (en) | A kind of di-n-butyl tin complex and its preparation method and application | |
| CN106220668B (en) | A kind of 2- carbonyls -3- phenylpropionic acids salicyloyl hydrazone di-n-butyl tin complex and its preparation method and application | |
| CN106220677B (en) | A kind of acylhydrazone organotin complex and its preparation method and application | |
| CN106380480B (en) | A kind of ALPHA-ketobutyric acid p-nitrophenyl formyl hydrazone stannous phenide complex and its preparation method and application | |
| CN106279252B (en) | A kind of 2- carbonyls -3- phenylpropionic acids benzoyl hydrazone di-n-butyl tin complex and its preparation method and application | |
| CN106279260B (en) | A kind of ALPHA-ketobutyric acid salicyloyl hydrazone di-n-butyl tin complex and its preparation method and application | |
| CN106220670B (en) | Two pairs of methylbenzyl tin complexs of one kind and its preparation method and application | |
| CN106366119B (en) | A kind of 2- carbonyls -2- phenylacetic acids are to methoxybenzoyl hydrazone di-n-butyl tin complex and its preparation method and application | |
| CN106366120B (en) | A kind of ALPHA-ketobutyric acid is to methoxybenzoyl hydrazone stannous phenide complex and its preparation method and application | |
| CN106220676B (en) | A kind of 2- carbonyl propionic acids are to methoxybenzoyl hydrazone Dibenzyltin complex and its preparation method and application | |
| CN106220672B (en) | A kind of di-n-butyl tin complex of the ligand containing acylhydrazone and its preparation method and application | |
| CN106220675B (en) | A kind of stannous phenide complex of the ligand containing acylhydrazone and its preparation method and application | |
| CN106220678B (en) | A kind of disubstituted benzyl tin complex and its preparation method and application | |
| CN106317105B (en) | A kind of 2- carbonyl -2- phenylacetic acid p-nitrophenyl formyl hydrazone di-n-butyl tin complex and its preparation method and application | |
| CN106366118B (en) | A kind of 2- carbonyl -2- phenylacetic acid is to tert-butyl benzoyl hydrazone stannous phenide complex and its preparation method and application | |
| CN106279250B (en) | A kind of stannous phenide complex and its preparation method and application | |
| CN106432322A (en) | 2-Carbonyl-2-phenylacetic acid p-nitrobenzoyl hydrazone diphenyltin complex, and preparation method and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |