CN106317082B - A kind of Rufloxacin (rhodanine beta-unsaturated ketone) amide derivatives and its preparation method and application - Google Patents
A kind of Rufloxacin (rhodanine beta-unsaturated ketone) amide derivatives and its preparation method and application Download PDFInfo
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- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
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Abstract
The invention discloses a kind of Rufloxacin (rhodanine beta-unsaturated ketone) amide derivatives and its preparation method and application, using such as following formula I chemical structure of general formula：
Description
Technical field
The invention belongs to original new drug synthesis technical fields, and in particular to a kind of Rufloxacin (rhodanine beta-unsaturated ketone) acyl
Amine derivant also relates to a kind of preparation method of Rufloxacin (rhodanine beta-unsaturated ketone) amide derivatives, and
Its application in antitumor drug.
Background technology
Discovery of the new drug innovation originating from primer, and the design of structure-based rational drug is the effective of discovery primer
Method.In the pharmacophore of various structures, five yuan of azoles heterocyclic ketones with extensive pharmacological activity have become medicine in particular about tannin
The advantage skeleton of object chemistry and the structure for being widely used in new drug molecular chemistry skeleton.Its include mainly 5- active methylene groups and
The condensation reaction of aldehyde forms C=C keys and the α that constructs, alpha, beta-unsaturated ketone derivative, at the same time 3- bit aminos and carboxylic acids split
Form the derivatives such as aminocarboxylic acids or amides.In addition, to improve the water solubility of Rhodanine derivant, taken in rhodanine skeleton
The modification side chain of multiamide base peptides is re-introduced on Dai Ji, to improve its bioavilability, promote it to patent medicine sexual development.Closely
Phase, using 1- substitutions -6- fluoro- quinoline (naphthyridines) -4- ketone -3- carboxylic acids as the antibacterial fluoroquinolone drug of advantage skeleton, based on its work
It is also the important function target of antitumor drug with target spot-topoisomerase, its antibacterial activity can be converted to antitumor work
Property.It is pharmacophore necessary to antitumor activity that structural modification research, which finds that fluoquinolone C-3 carboxyls are not, with C-3 acylamino-s
For connection chain carry another antitumor activity pharmacophore, it can be achieved that different pharmacophore activity superposition, and be found that with anti-
The candidate compound of tumor promotion.However, the beta-unsaturated ketone amides that fluoquinolone skeleton is built with rhodanine skeleton phase split
The compound of structure is not yet reported.
For this purpose, the object of the present invention is to provide a kind of Rufloxacin (rhodanine beta-unsaturated ketone) amide derivatives, have
Antineoplastic action and effect, while a kind of preparation side of Rufloxacin (rhodanine beta-unsaturated ketone) amide derivatives being provided
Method.
In order to achieve the goal above, the technical solution adopted in the present invention is：A kind of Rufloxacin (rhodanine unsaturation
Ketone) amide derivatives, chemical structural formula is as shown in logical formula (I)：
Ar is phenyl ring or substituted benzene ring or furan nucleus or pyridine ring.Such compound is the chemical combination of concrete structure below
Object：
The preparation method of a kind of Rufloxacin (rhodanine beta-unsaturated ketone) amide derivatives of the present invention, with formula (II) institute
The Rufloxacin shown is prepared as a raw material,
Specific preparation process is as follows：
1) with hydrazine hydrate hydrazinolysis is occurred into for Rufloxacin shown in formula (II) and reacts Rufloxacin acyl shown in obtained formula (III)
Hydrazine；
Concrete operation step is：Rufloxacin (20.0g, 55.0mmol) and 85% hydrazine hydrate (50mL) and absolute ethyl alcohol
The mixture back flow reaction of (100mL) 24 hours.Placement is cooled to room temperature, and filter collection solid is recrystallized with absolute ethyl alcohol, obtains yellow
Crystallization formula (III), yield 87%, 224~226 DEG C of mp.1H NMR(400MHz,CDCl3)δ:11.35(1H,s,CONH),8.93
(1H,s,2-H),7.84(1H,d,5-H),4.68(2H,t,SCH2),4.55(2H,s,NH2), 3.43~3.14 (10H, m,
NCH2and piperazine-H),2.32(3H,s,N-CH3)；MS(m/z):Calcd.for C17H20F3N5O2S:377.44[M
]+；Found:378[M+H]+。
2) Rufloxacin hydrazide compound shown in formula (III) and double-(carboxymethyl) trithiocarbonate are flowed back in water
Room temperature, ammonium hydroxide alkalization are placed in reaction 12 hours, and filtering is collected the solid of generation, recrystallized with DMF solvent, and formula (IV) institute is made
Rufloxacin (rhodanine) amide intermediate shown.
Concrete operation step is：Rufloxacin hydrazides (10.0g, 27.0mmol) and double-(carboxymethyl) trithiocarbonate
(7.2g, 31.0mmol) disappears in water (300mL) back flow reaction to raw material, and (TLC is detected, VChloroform：VMethanol=5:1).Cooling room temperature,
It is alkalized to pH 8.0~9.0 with concentrated ammonia liquor, placement is cooled to room temperature.The solid that filter collection generates, it is dry.Crude product absolute ethyl alcohol weight
Crystallization, obtains yellow crystal formula (IV), yield 66.7%, 230~232 DEG C of mp.1H NMR(400MHz,CDCl3):δ:11.37
(1H, s, CONH), 8.91 (1H, s, 2-H), 7.82 (1H, d, 5-H), 4.72~4.63 (4H, m, 2 × SCH2), 3.40~3.12
(10H,m,NCH2and piperazine-H),2.32(3H,s,N-CH3)；MS(m/z):Calcd.for C20H20FN5O3S3:
493.60[M]+；Found:494[M+H]+。
4) by Rufloxacin (rhodanine) amide compound shown in formula (IV) and aromatic aldehyde under the catalysis of alkali in glacial acetic acid
Middle carry out condensation reaction, after complete reaction through handle shown in target compound such as formula (I).
Ar is phenyl ring or substituted benzene ring or furan nucleus or pyridine ring.
The general operating procedure that is synthetically prepared is：Take the fluoro- 8,1- of 6- (sulphur ethyl) -7- (4- thyl-piperazin -1- bases)-quinoline
(1H) -one of quinoline-4-3- (2- thioxo-thiazolidin-4- ketone-3- bases]-amide (IV) 1.0g (2.0mmol) and anhydrous sodium acetate
0.20g (2.4mmol) is dissolved in 15mL glacial acetic acids, and aromatic aldehyde (2.0mmol), mixed reactant back flow reaction 12h is added.Subtract
Pressure is evaporated off solvent, and residue is dissolved with water (20mL), and suitable activated carbon is added and decolourize at 60 DEG C 0.5h, filters.Filtrate is with dense
Ammonium hydroxide alkalizes to pH 9.0, with chloroform recovery (3 × 15mL), merges organic phase, anhydrous sodium sulfate drying.Solvent is recovered under reduced pressure extremely
It is dry, with ethyl alcohol-DMF (V:V=5:1) it recrystallizes, obtains pale yellow crystals object (I).
As a further improvement, (rhodanine) amide of Rufloxacin shown in formula IV and aromatic aldehyde mole is 1:1.0
~1.2.
The alkali is at least one of pyridine, triethylamine, piperidines, morpholine, potassium acetate and sodium acetate.
A kind of described Rufloxacin (rhodanine beta-unsaturated ketone) amide derivatives answering in the preparation of antitumor drugs
With.
The antitumor drug is treatment liver cancer, cancer of pancreas or leukemia medicament.
A kind of principle of hybridization of Rufloxacin (rhodanine beta-unsaturated ketone) amide derivatives based on pharmacophore of the present invention,
By tricyclic fluoroquinolone, amide and rhodanine α, the effective combination between the difference pharmacophore such as alpha, beta-unsaturated ketone, and then devise
Rufloxacin (rhodanine beta-unsaturated ketone) amide derivatives realize the complementation of different structure pharmacophore and active superposition,
To achieve synergistic and detoxifying effects, the antitumor drug exploitation of brand new can be used as.
Specific implementation mode
The technical scheme of the invention is described in detail through specific implementation examples.
Embodiment 1
The fluoro- 8,1- of 6- (sulphur ethyl) -7- (4- thyl-piperazin -1- bases)-quinoline -4 (1H) -one -3- (thio -5- benzene first of 2-
Pitch base-thiazolidin-4-one -3- bases]-amide (I-1), chemical structural formula is：
Ar i.e. in Formulas I is phenyl.
The preparation method of the compound is：Aromatic aldehyde is substituted with benzaldehyde (0.23g, 2.2mmol), according to above-mentioned target
The general preparative methods of object (I) obtain target pale yellow crystals object (I-1), 228~230 DEG C of mp.1H NMR(400MHz,
CDCl3):δ:11.37 (1H, s, CONH), 8.91 (1H, s, 2-H), 7.82 (1H, d, 5-H), 4.72~4.63 (4H, m, 2 ×
SCH2), 3.40~3.12 (10H, m, NCH2and piperazine-H),2.32(3H,s,N-CH3)；MS(m/z):
Calcd.for C27H24FN5O3S3:581.71[M]+；Found:582[M+H]+。
Embodiment 2
(thio -5- of 2- are to first by-quinoline -4 (1H) -one -3- by the fluoro- 8,1- of 6- (sulphur ethyl) -7- (4- thyl-piperazin -1- bases)
Oxygroup benzene methene base-thiazolidin-4-one -3- bases]-amide (I-2), chemical structural formula is：
Ar i.e. in Formulas I is p-methoxyphenyl.
The preparation method of the compound is：Aromatic aldehyde is substituted with P-methoxybenzal-dehyde (0.30g, 2.2mmol), according to upper
The general preparative methods for the object (I) stated obtain target pale yellow crystals object (I-2), yield 87.3%, m.p.234~236
℃。1H NMR(400MHz,CDCl3)δ:11.38 (1H, s, CONH), 8.93 (1H, s, 2-H), 8.23 (1H, s, CH=), 7.85
~7.53 (5H, m, 5-H and Ph-H), 4.74~4.67 (4H, m, 2 × SCH2),3.87(s,3H,OCH3), 3.42~3.15
(10H,m,NCH2and piperazine-H),2.34(3H,s,N-CH3)；MS(m/z):Calcd.for C28H26FN5O4S3:
611.74[M]+；Found:612[M+H]+。
Embodiment 3
The fluoro- 8,1- of 6- (sulphur ethyl) -7- (4- thyl-piperazin -1- bases)-quinoline -4 (1H) -one -3- [thio -5- of 2- (3,
4- dioxymethylenes) benzene methene base-thiazolidin-4-one -3- bases]-amide (I-3), chemical structural formula is：
Ar i.e. in Formulas I is 3,4- (dioxymethylene) base phenyl.
The preparation method of the compound is：Aromatic aldehyde is substituted with 3,4-methylenedioxy benzaldehyde (0.3g, 2.0mmol),
According to the general preparative methods of above-mentioned object (I), target pale yellow crystals object (I-3), yield 92.6%, m.p.241 are obtained
~243 DEG C.1H NMR(400MHz,CDCl3)δ:11.41 (1H, s, CONH), 8.95 (1H, s, 2-H), 8.24 (1H, s, CH=),
7.86~7.68 (4H, m, 5-H and Ph-H), 6.31 (s, 2H, OCH2), O 4.75~4.68 (4H, m, 2 × SCH2), 3.43~
3.21(10H,m,NCH2and piperazine-H),2.36(3H,s,N-CH3)；MS(m/z):Calcd.for
C28H24FN5O5S3:625.72[M]+；Found:626[M+H]+。
Embodiment 4
The fluoro- 8,1- of 6- (sulphur ethyl) -7- (4- thyl-piperazin -1- bases)-quinoline -4 (1H) -one -3- [thio -5- of 2- (3,
4,5- trimethoxy methyl) benzene methene base-thiazolidin-4-one -3- bases]-amide (I-4), chemical structural formula is：
Ar i.e. in Formulas I is 3,4,5- trimethoxy methylene phenyl.
The preparation method of the compound is：Aromatic aldehyde is substituted with 3,4,5-Trimethoxybenzaldehyde (0.43g, 2.2mmol),
According to the general preparative methods of above-mentioned object (I), pale yellow crystals object (I-4), yield 78.8%, m.p.232 are obtained
~234 DEG C.1H NMR(400MHz,CDCl3)δ:11.38 (1H, s, CONH), 8.94 (1H, s, 2-H), 8.25 (1H, s, CH=),
8.18 (1H, d, 5-H), 7.86 (2H, s, Ph-H), 4.73~4.66 (4H, m, 2 × SCH2),3.86,3.88(9H,2s,3×
OCH3), 3.43~3.21 (10H, m, NCH2and piperazine-H),2.35(3H,s,N-CH3)；MS(m/z):
Calcd.for C30H30FN5O6S3:671.79[M]+；Found:672[M+H]+。
Embodiment 5
(thio -5- of 2- are to fluorine by-quinoline -4 (1H) -one -3- by the fluoro- 8,1- of 6- (sulphur ethyl) -7- (4- thyl-piperazin -1- bases)
Benzene methene base-thiazolidin-4-one -3- bases)-amide (I-5), chemical structural formula is：
Ar i.e. in Formulas I is p-fluorophenyl.
The preparation method of the compound is：Aromatic aldehyde is substituted with 4-Fluorobenzaldehyde (0.27g, 2.2mmol), according to above-mentioned
The general preparative methods of object (I) obtain pale yellow crystals object (I-5), yield 80.5%, m.p.238~238 DEG C.1H
NMR(400MHz,CDCl3)δ:11.43 (1H, s, CONH), 8.95 (1H, s, 2-H), 8.27 (s, 1H, CH=), 8.13~7.68
(5H, m, 5-H and Ph-H), 4.76~4.68 (4H, m, 2 × SCH2), 3.46~3.20 (10H, m, NCH2and
piperazine-H),2.36(3H,s,N-CH3)；MS(m/z):Calcd.for C27H23F2N5O3S3:599.70[M]+；
Found:600[M+H]+。
Embodiment 6
(thio -5- of 2- are to nitre by-quinoline -4 (1H) -one -3- by the fluoro- 8,1- of 6- (sulphur ethyl) -7- (4- thyl-piperazin -1- bases)
Base benzene methene base-thiazolidin-4-one -3- bases)-amide (I-6), chemical structural formula is：
Ar i.e. in Formulas I is p-nitrophenyl.
The preparation method of the compound is：Aromatic aldehyde is substituted with paranitrobenzaldehyde (0.30g, 2.0mmol), according to above-mentioned
Object (I) general preparative methods, obtain pale yellow crystals object (I-6), yield 73.6%, m.p.242~244 DEG C.1H NMR(400MHz,CDCl3)δ:1H NMR(400MHz,CDCl3)δ:11.46(1H,s,CONH),8.97(1H,s,2-H),
8.31 (s, 1H, CH=), 8.21~7.86 (5H, m, 5-H and Ph-H), 4.78~4.73 (4H, m, 2 × SCH2), 3.48~
3.22(10H,m,NCH2and piperazine-H),2.38(3H,s,N-CH3)；MS(m/z):Calcd.for
C27H23FN6O5S3:626.71[M]+；Found:627[M+H]+。
Embodiment 7
The fluoro- 8,1- of 6- (sulphur ethyl) -7- (4- thyl-piperazin -1- bases)-quinoline -4 (1H) -one -3- (thio -5- pyrroles of 2-
Pyridine -4- methenes base-thiazolidin-4-one -3- bases)-amide (I-7), chemical structural formula is：
Ar i.e. in Formulas I is 4- pyridyl groups.
The preparation method of the compound is：Aromatic aldehyde is substituted with Pyridine-4-Carboxaldehyde (0.24g, 2.2mmol), according to above-mentioned
Object (I) general preparative methods, obtain pale yellow crystals object (I-7), yield 65.4%, m.p.233~235 DEG C.1H NMR(400MHz,CDCl3)δ:11.46(1H,s,CONH),9.23(1H,s,2-H),9.07(2H,d,Py-H),8.84(2H,
D, 2H, Py-H), 8.65 (1H, s, CH=), 8.23 (1H, d, 1H, 5-H), 4.81~4.76 (4H, m, 2 × SCH2), 3.53~
3.28(10H,m,NCH2and piperazine-H),2.41(3H,s,N-CH3)；MS(m/z):Calcd.for
C26H23FN6O3S3:582.70[M]+；Found:583[M+H]+。
Embodiment 8
The fluoro- 8,1- of 6- (sulphur ethyl) -7- (4- thyl-piperazin -1- bases)-quinoline -4 (1H) -one -3- (thio -5- furans of 2-
Mutter -2- methenes base-thiazolidin-4-one -3- bases)-amide (I-8), chemical structural formula is：
Ar i.e. in Formulas I is 2- furyls.
The preparation method of the compound is：Aromatic aldehyde is substituted with furans -2- formaldehyde (furfural) (0.21g, 2.2mmol), according to
According to the general preparative methods of above-mentioned object (I), pale yellow crystals object (I-8) is obtained, yield 60.8%, m.p.231~
233℃。1H NMR(400MHz,CDCl3)δ:15.53(1H,br,COOH),11.42(s,1H,CONH),9.15(s,1H,2-H),
8.33 (s, 1H, CH=), 8.17 (d, J=12.8Hz, 1H, 5-H), 7.76~7.13 (m, 3H, furan-H), 4.83~4.78
(4H,m,2×SCH2), 3.55~3.30 (10H, m, NCH2and piperazine-H),2.43(3H,s,N-CH3)；MS(m/
z):Calcd.for C25H22FN5O4S3:571.68[M]+；Found:572[M+H]+。
Embodiment 9
(thio -5- of 2- are to carboxylic by-quinoline -4 (1H) -one -3- by the fluoro- 8,1- of 6- (sulphur ethyl) -7- (4- thyl-piperazin -1- bases)
Base phenyl -2- methenes base-thiophene
Oxazolidine -4- ketone -3- bases)-amide (I-9), chemical structural formula is：
Ar i.e. in Formulas I is 4- carboxyl phenyls.
The preparation method of the compound is：Aromatic aldehyde is substituted with p -carboxybenzaldehyde (0.33g, 2.2mmol), according to above-mentioned
Object (I) general preparative methods, obtain pale yellow crystals object (I-9), yield 72.0%, m.p.244~246 DEG C.1H NMR(400MHz,CDCl3)δ:15.46(brs,1H,COOH),11.46(s,1H,CONH),9.21(s,1H,2-H),8.48
(d, J=7.2Hz, 2H, Ph-H), 8.36 (s, 1H, CH=), 8.23 (d, J=12.8Hz, 1H, 5-H), 7.88 (d, J=
7.2Hz, 2H, Ph-H), 4.86~4.82 (4H, m, 2 × SCH2), 3.57~3.35 (10H, m, NCH2and piperazine-
H),2.44(3H,s,N-CH3)；MS(m/z):Calcd.for C28H24FN5O5S3:625.72[M]+；Found:626[M+H]+。
Embodiment 10
The fluoro- 8,1- of 6- (sulphur ethyl) -7- (4- thyl-piperazin -1- bases)-quinoline -4 (1H) -one -3- carboxylic acids (thio -5- of 2-
To sulfonamido phenyl -2- methenes base-thiazolidin-4-one -3- bases)-amide (I-10), chemical structural formula is：
Ar i.e. in Formulas I is 4- sulfoamido phenyl.
The preparation method of the compound is：To substitute aromatic aldehyde to sulfamoyl benzaldehyde (0.37g, 2.0mmol), according to
The general preparative methods of above-mentioned object (I), obtain pale yellow crystals object (I-10), yield 72.4%, and m.p.246~
248℃。1H NMR(400MHz,CDCl3)δ:11.53(1H,s,CONH),9.26(1H,s,2-H),8.35(2H,d,Ph-H),
8.35 (1H, s, CH=), 8.22 (1H, d, 5-H), 8.09 (2H, d, 2H, Ph-H), 7.76 (2H, s, NH2), 4.88~4.83
(4H,m,2×SCH2), 3.61~3.37 (10H, m, NCH2and piperazine-H),2.46(3H,s,N-CH3)；MS(m/
z):Calcd.for C27H25FN6O5S4:660.79[M]+；Found:661[M+H]+。
Test example
One, a kind of Rufloxacin (rich tannin beta-unsaturated ketone) amide derivatives of embodiment 1-10 offers is external anti-swollen
Tumor activity measures 1, test sample
A kind of Rufloxacin (the rich tannin beta-unsaturated ketone) amide derivatives provided with embodiment 1-10, and it is classical anti-swollen
Tumor TOPO inhibitor 10-hydroxycamptothecine (HC) and Rufloxacin (LFX) are test sample, and totally 12 kinds, wherein HC and LFX are pair
According to group, embodiment 1-10 samples are experimental group；
Experimental cancer cell line is respectively human liver cancer Hep-3B cells, human pancreas cancer Panc-1 cells and human leukemia HL60 thin
Born of the same parents' strain is purchased from Shanghai Cell Bank of the Chinese Academy of Sciences.Normal cell uses VERO African green monkey kidney cells, purchase logical in Shanghai
Growth Science and Technology Ltd..
2, assay method
Assay method the specific steps are：
(1) it uses dimethyl sulfoxide (DMSO) (DMSO) to dissolve respectively above-mentioned 12 kinds of test samples first, is configured to 1.0 × 10- 2mol·L-1The storing solution of concentration uses the RPMI-1640 culture solutions that mass percent concentration is 10% calf serum will later
Storing solution is diluted to 5 concentration gradients (0.1,1.0,5.0,10.0,50.0 μm of olL-1) working solution；
Human liver cancer Hep-3B cells, human pancreas cancer Panc-1 cells and the human leukemia HL60 cells of logarithmic growth phase and
VERO cell strains, with 6000, every hole cell inoculation in 96 orifice plates, be then separately added into above-mentioned 12 kinds of samples has 5 concentration
5gL is added in the working solution of gradient per hole after 48 hours–110 μ L of MTT (tetrazolium bromide) solution are added 100 after continuing culture 4 hours
Lauryl sodium sulfate (SDS) hydroponics that μ L mass percent concentrations are 10% 24 hours, then use microplate reader in 570nm
Respective absorbance (OD) value is measured at wavelength；
(3) inhibiting rate of the test sample to cancer cell of various concentration is calculated by using the formula shown below,
Cancer inhibition rate=[(1- experimental group OD values)/control group OD values] × 100%,
Then linear regression is made to the corresponding cancer inhibition rate of each concentration with the logarithm of each concentration of test sample, obtained
To dose-effect equation, half-inhibition concentration of each test sample to experiment cancer cell is calculated from gained dose-effect equation
(IC50)；Each data parallel determination three times, is averaged, the results are shown in Table 1.
Antitumor activity (the IC of 1 each test sample of table50)
As it can be seen from table 1 the compound that embodiment 1-10 is provided is significantly stronger than the inhibitory activity for testing 3 kinds of cancer cells
The activity of parent compound Rufloxacin, wherein most compound are thin to human liver cancer Hep-3B cells and human pancreas cancer Panc-1
The activity of born of the same parents is better than the activity of control hydroxycamptothecin, IC50Value has reached micro-molar concentration.What makes more sense is that embodiment 1-
10 compounds provided show low toxicity VERO cells, the potentiality with druggability.Therefore, according to drug development
General way is first to carry out conventional antitumor in-vitro screening, is then targetedly studied, so the compound of the present invention
It, can be by being mixed with acid human-acceptable at salt or with pharmaceutical carrier with strong antitumor activity and lower toxicity
Antitumor drug.
Claims (6)
1. a kind of Rufloxacin (rhodanine beta-unsaturated ketone) amide derivatives, are typically characterized by the chemical combination with lower structure
Object：
2. a kind of preparation method of Rufloxacin (rhodanine beta-unsaturated ketone) amide derivatives according to claim 1,
It is characterized in that, specific preparation process includes：
(1) it using Rufloxacin shown in formula (II) as raw material, is reacted through hydrazinolysis and Rufloxacin hydrazides shown in formula (III) is made.
(2) Rufloxacin hydrazide compound shown in formula (III) and double-(carboxymethyl) trithiocarbonate are flowed back 24 in water
Hour, condensation reaction occurs, it is after reaction, post-treated to obtain Rufloxacin (rhodanine) amides shown in formula (IV) and spread out
Biology；Then formula (IV) forms 5- virtue methene base rhodanine α, alpha, beta-unsaturated ketone knot with aromatic aldehyde under the catalysis of weak base sodium acetate
Structure, it is post-treated to obtain a kind of Rufloxacin (rhodanine beta-unsaturated ketone) amide derivatives shown in formula (I).
Wherein, aromatic aldehyde selects benzaldehyde corresponding with embodiment, P-methoxybenzal-dehyde, 3,4- dioxymethylene benzene first
Aldehyde, 3,4,5-trimethoxybenzaldehyde, 4-Fluorobenzaldehyde, paranitrobenzaldehyde, 4- pyridine carboxaldehydes, 2 furan carboxyaldehyde, to carboxyl
Benzaldehyde and to sulfoamido benzaldehyde；In formula I Ar be phenyl, p-methoxyphenyl, 3,4- (dioxymethylene) phenyl, 3,4,
5- trimethoxyphenyls, p-fluorophenyl, p-nitrophenyl, 4- pyridyl groups, 2- furyls, to carboxyl phenyl or to sulfoamido benzene
Base.
3. a kind of preparation method of Rufloxacin (rhodanine beta-unsaturated ketone) amide derivatives according to claim 2,
It is characterized in that, mole of Rufloxacin hydrazides shown in the formula (III) and double-(carboxymethyl) trithiocarbonate compound
Than being 1:1.0~1.2.
4. a kind of preparation method of Rufloxacin (rhodanine beta-unsaturated ketone) amide derivatives according to claim 2,
It is characterized in that, the molar ratio of Rufloxacin (rhodanine) amide and aromatic aldehyde shown in the formula (IV) is 1:1.0~1.2.
5. a kind of Rufloxacin (rhodanine beta-unsaturated ketone) amide derivatives as described in claim 1 are preparing antitumor drug
In application.
6. a kind of Rufloxacin (rhodanine beta-unsaturated ketone) amide derivatives according to claim 5 are preparing antineoplastic
Application in object, which is characterized in that the antitumor drug is the drug for treating liver cancer, cancer of pancreas or leukaemia.
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