CN106316944A - Alpha, beta-nonsaturated ketone derivative of fleroxacin, preparation method and application thereof - Google Patents

Alpha, beta-nonsaturated ketone derivative of fleroxacin, preparation method and application thereof Download PDF

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CN106316944A
CN106316944A CN201510369759.1A CN201510369759A CN106316944A CN 106316944 A CN106316944 A CN 106316944A CN 201510369759 A CN201510369759 A CN 201510369759A CN 106316944 A CN106316944 A CN 106316944A
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fleroxacin
beta
alpha
unsaturated ketone
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CN106316944B (en
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胡国强
闫强
吴书敏
倪礼礼
杨彤
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Henan University
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D215/20—Oxygen atoms
    • C07D215/22—Oxygen atoms attached in position 2 or 4
    • C07D215/233—Oxygen atoms attached in position 2 or 4 only one oxygen atom which is attached in position 4
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms

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Abstract

The invention discloses an alpha, beta-nonsaturated ketone derivative of fleroxacin, a preparation method and an application thereof. According to the invention, a chemical structural general formula is employed as a following formula I, in the formula I, aromatic ring Ar is phenyl ring or substituted phenyl ring or furan ring or pyridine ring. The alpha, beta-nonsaturated ketone derivative of fleroxacin realizes effective combination of fluoronaphthalene quinacridone frame and alpha, beta-nonsaturated ketone frame, a novel fluoronaphthalene quinacridone-chalcone compound is constructed, so that the antineoplastic activity of the novel compound is increased, toxic and side effects on the normal cells are reduced, and the derivative can be taken as an antineoplastic active substance for developing the antitumor drugs with a brand new structure.

Description

A kind of α of fleroxacin, alpha, beta-unsaturated ketone derivant and its preparation method and application
Technical field
The invention belongs to original new drug synthesis technical field, be specifically related to the α of a kind of fleroxacin, alpha, beta-unsaturated ketone derivant, with Time further relate to the α of a kind of fleroxacin, the preparation method of alpha, beta-unsaturated ketone derivant, and its application in antitumor drug.
Background technology
New drug innovation originates from the discovery of primer, and rational drug MOLECULE DESIGN based on structure is to find the effective ways of primer. In the pharmacophore of various structures, there is α, the chalcone compounds of alpha, beta-unsaturated ketone architectural feature as important natural effectively Composition, is concerned because having multiple pharmacologically active.But, natural chalcone compounds mostly is the cyclosubstituted α of polyhydroxy benzenes, Beta-unsaturated ketone compound, because its poor water solublity causes bioavailability relatively low, limits application clinically.It addition, Also it is the important function target spot of antitumor drug in conjunction with the action target spot topoisomerase of antibacterial flouroquinolone drugs, can be resisted Bacterium is active Transforming for anti-tumor activity, and find fluoroquinolone C-3 carboxyl be not pharmacophore necessary to anti-tumor activity, can Replace by bioisostere to improve its anti-tumor activity.Based on this, for improving the water solublity of chalcones, improve it raw Thing availability and activity, present invention advantage pharmacophore polyfluoro quinoline-4 (1H) the-one skeleton of flouroquinolone drugs fleroxacin is made For α, the substituent group of alpha, beta-unsaturated ketone structure, and then devise fluoroquinolone " class chalcone " derivant of new structure.
To this end, it is an object of the invention to provide the α of a kind of fleroxacin, alpha, beta-unsaturated ketone derivant, have antineoplastic action and Effect, provides the α of a kind of fleroxacin, the preparation method of alpha, beta-unsaturated ketone derivant simultaneously.
In order to realize object above, the technical solution adopted in the present invention is: the α of a kind of fleroxacin, alpha, beta-unsaturated ketone derivant, Its chemical structural formula is as shown in formula I:
In formula I, Ar is phenyl ring or substituted benzene ring or furan nucleus or pyridine ring, and this compounds is the compound of following concrete structure:
The α of a kind of fleroxacin of the present invention, the preparation method of alpha, beta-unsaturated ketone derivant, is former with the fleroxacin shown in formula II Material is prepared from；
Concrete preparation process is as follows:
1) compound shown in formula III is reacted to obtain with the fleroxacin shown in formula II through sodium borohydride reduction decarboxylation, then with formic acid Ethyl ester condensation reaction prepares the compound shown in formula IV, and last formula IV and activated manganese dioxide aoxidize to obtain formula V fleroxacin aldehyde；
Step 1) Detailed operating procedures be referred to document (Kondo H, Sakamoto F, et al.Studies on prodrugs.7. Synthesis and antimicrobial activity of 3-formylquinolone derivatives,J.Med.Chem.1988,31, 221～225.) the prodrug research synthesis of .7.3-formoxyl Carbostyril derivative and antimicrobial acivity) method prepare, detailed process As follows:
2) fleroxacin aldehyde shown in formula V is carried out hydroxyl with the aromatic radical ethyl ketone shown in formula VI under the catalysis of alkali in dehydrated alcohol Aldehyde condensation reaction, after question response is complete, the treated target compound that obtains is as shown in formula I, and detailed process is as follows:
Wherein, in formula I, Ar is phenyl ring or substituted benzene ring or furan nucleus or pyridine ring.
The general synthetically prepared operating procedure of target compound formula I is: take 6, the fluoro-1-of 8-bis-(2-fluoro ethyl)-7-(4-thyl-piperazin -1-base)-quinoline-4 (1H)-one-3-formaldehyde formula V 1.1g (3.2mmol) is dissolved in 20mL dehydrated alcohol, adds aromatic radical ethyl ketone Formula VI (3.2mmol) and base catalyst piperidines (0.1mL).Mixed reactant back flow reaction 24h, places room temperature, and filter collection produces Solid, dehydrated alcohol recrystallization, obtain pale yellow crystals object formula I.
As further improving, the fleroxacin aldehyde shown in formula V is 1:1.0～1.2 with the mol ratio of aromatic radical ethyl ketone formula VI.
Described base catalyst is at least one in piperidines, pyridine, triethylamine, morpholine, potassium acetate and sodium acetate.
The α of described a kind of fleroxacin, the application in preparing antitumor drug of the alpha, beta-unsaturated ketone derivant.
Described antitumor drug is treatment hepatocarcinoma, cancer of pancreas or leukemia medicament.
The α of a kind of fleroxacin of the present invention, alpha, beta-unsaturated ketone derivant principle of hybridization based on pharmacophore, by many fluoroquinolones bone Frame and α, alpha, beta-unsaturated ketone pharmacophore is effectively combined, and design has synthesized the α of fleroxacin, alpha, beta-unsaturated ketone derivant, it is achieved The complementation of different structure pharmacophore and the superposition of activity, thus reached the effect of potentiation toxicity reduction, can anti-as brand new Tumour medicine is developed.
Detailed description of the invention
Below by specific embodiment, technical scheme is described in detail.
Embodiment 1
6,8-bis-fluoro-1-(2-fluoro ethyl)-7-(4-thyl-piperazin-1-base)-3-(2-benzoyl-ethylene-1-base)-quinoline-4 (1H)-one (I-1), Its chemical structural formula is:
I.e. Ar in formula I is phenyl.
The preparation method of this compound is: substitute aromatic radical ethyl ketone (VI) with 1-Phenylethanone. (0.45g, 3.8mmol), according to above-mentioned mesh The general preparative methods of mark thing (I), obtains pale yellow crystals object (I-1), productivity 73.2%, m.p.161～163 DEG C.1H NMR(400 MHz,CD3Cl) δ: 2.34～2.38 (7H, m, piperazine-H and N-CH3), 3.42 (4H, t, piperazine-H), 4.68～4.82 (4H, M, FCH2CH2N), 7.53～8.03 (6H, m, Ph-H and 5-H), 8.18～8.87 (3H, m, 2-H, 1 '-H and 2 '-H)； MS (m/z): 456 [M+H]+, calculate (C25H24F3N3O2): 455.48.
Embodiment 2
6,8-bis-fluoro-1-(2-fluoro ethyl)-7-(4-thyl-piperazin-1-base)-3-[2-(4-methoxybenzoyl)-ethylene-1-base]-quinoline -4 (1H)-one (I-2), its chemical structural formula is:
I.e. Ar in formula I is p-methoxyphenyl.
The preparation method of this compound is: substitutes aromatic radical ethyl ketone formula VI with 4-methoxy-acetophenone (0.48g, 3.2mmol), depends on According to the general preparative methods of above-mentioned object formula I, obtain pale yellow crystals object (I-2), productivity 76.4%, m.p.164～166 DEG C.1H NMR(400MHz,CD3Cl) δ: 2.35～2.42 (7H, m, piperazine-H and N-CH3), 3.43 (4H, t, piperazine-H), 4.72～4.84 (4H, m, FCH2CH2N), 3.86 (3H, s, OCH3), 7.66～8.06 (5H, m, Ph-H and 5-H), 8.21～8.88 (3H, m, 2-H, 1 '-H and 2 '-H)；MS (m/z): 486 [M+H]+, calculate (C26H26F3N3O3): 485.51.
Embodiment 3
6,8-bis-fluoro-1-(2-fluoro ethyl)-7-(4-thyl-piperazin-1-base)-3-[2-(3,4-dioxymethylene-benzoyl)-ethylene-1-base]- Quinoline-4 (1H)-one (I-3), its chemical structural formula is:
I.e. Ar in formula I is 3,4-(dioxymethylene) phenyl.
The preparation method of this compound is: with 3, and 4-dioxymethylene-1-Phenylethanone. (0.52g, 3.2mmol) substitutes aryl methyl ketone formula VI, according to the general preparative methods of above-mentioned object formula I, obtain pale yellow crystals object thing (I-3), productivity 72.6%, m.p. 178～180 DEG C.1H NMR(400MHz,CD3Cl) δ: 2.35～2.46 (7H, m, piperazine-H and N-CH3), 3.46 (4H, T, piperazine-H), 4.72～4.86 (4H, m, FCH2CH2N), 6.22 (2H, s, OCH2O), 7.67～8.12 (5H, m, Ph-H And 5-H), 8.23～8.97 (3H, m, 2-H, 1 '-H and 2 '-H)；MS (m/z): 500 [M+H]+, calculate (C26H24F3N3O4): 499.49。
Embodiment 4
6,8-bis-fluoro-1-(2-fluoro ethyl)-7-(4-thyl-piperazin-1-base)-3-[2-(3,4,5-trimethoxy methyl-benzoyl)-ethylene-1-base]- Quinoline-4 (1H)-one (I-4), its chemical structural formula is:
I.e. Ar in formula I is 3,4,5-2,4,5-trimethoxyphenyls.
The preparation method of this compound is: with 3, and 4,5-trimethoxies-1-Phenylethanone. (0.67g, 3.2mmol) substitutes aromatic radical ethyl ketone Formula VI, according to the general preparative methods of above-mentioned object formula I, obtains pale yellow crystals object thing (I-4), productivity 63.7%, M.p.158～160 DEG C.1H NMR(400MHz,CD3Cl) δ: 2.36～2.48 (7H, m, piperazine-H and N-CH3), 3.50 (4H, T, piperazine-H), 4.74～4.88 (4H, m, FCH2CH2N), 3.86,3.88 (9H, 2s, 3 × OCH3), 7.76～8.15 (3H, M, Ph-H and 5-H), 8.26～9.03 (3H, m, 2-H, 1 '-H and 2 '-H)；MS (m/z): 546 [M+H]+, calculate (C28H30F3N3O5): 545.56.
Embodiment 5
6,8-bis-fluoro-1-(2-fluoro ethyl)-7-(4-thyl-piperazin-1-base)-3-[2-(4-methyl-benzoyl)-ethylene-1-base]-quinoline-4 (1H)- Ketone (I-5), its chemical structural formula is:
I.e. Ar in formula I is to methylphenyl.
The preparation method of this compound is: substitute aromatic radical ethyl ketone formula VI with 4-methyl-acetophenone (0.51g, 3.8mmol), according to The general preparative methods of above-mentioned object formula I, obtains pale yellow crystals object thing (I-5), productivity 56.4%, m.p. 144～146 DEG C.1H NMR(400MHz,CD3Cl) δ: 2.24～2.46 (10H, m, Ph-CH3, piperazine-H and N-CH3), 3.47 (4H, t, piperazine-H), 4.72～4.83 (4H, m, FCH2CH2N), 7.62～8.03 (5H, m, Ph-H and 5-H), 8.17～8.94 (3H, m, 2-H, 1 '-H and 2 '-H)；MS (m/z): 470 [M+H]+, calculate (C26H26F3N3O2): 469.51.
Embodiment 6
6,8-bis-fluoro-1-(2-fluoro ethyl)-7-(4-thyl-piperazin-1-base)-3-[2-(the fluoro-benzoyl of 4-)-ethylene-1-base]-quinoline-4 (1H)- Ketone (I-6), its chemical structural formula is:
I.e. Ar in formula I is to fluoro-phenyl.
The preparation method of this compound is: substitute aromatic radical ethyl ketone formula VI with the fluoro-1-Phenylethanone. of 4-(0.44g, 3.2mmol), according to upper The general preparative methods of the object formula I stated, obtains pale yellow crystals object thing (I-6), productivity 76.2%, m.p.175～177 DEG C.1H NMR(400MHz,CD3Cl) δ: 2.36～2.56 (7H, m, piperazine-H and N-CH3), 3.53 (4H, t, piperazine-H), 4.82～4.87 (4H, m, FCH2CH2N), 7.78～8.16 (5H, m, Ph-H and 5-H), 8.25～9.13 (3H, m, 2-H, 1 '-H and 2 '-H)；MS (m/z): 474 [M+H]+, calculate (C25H23F4N3O2): 473.47.
Embodiment 7
6,8-bis-fluoro-1-(2-fluoro ethyl)-7-(4-thyl-piperazin-1-base)-3-[2-(4-nitro-benzoyl)-ethylene-1-base]-quinoline-4 (1H)- Ketone (I-7), its chemical structural formula is:
I.e. Ar in formula I is p-nitrophenyl.
The preparation method of this compound is: substitute aromatic radical ethyl ketone formula VI with 4-nitro-acetophenone (0.53g, 3.2mmol), according to The general preparative methods of above-mentioned object formula I, obtains pale yellow crystals object thing (I-7), productivity 78.2%, m.p. 185～187 DEG C.1H NMR(400MHz,CD3Cl) δ: 2.38 (3H, s, N-CH3), 2.65～3.56 (8H, m, piperazine-H), 4.86～4.97 (4H, m, FCH2CH2N), 7.84～8.18 (5H, m, Ph-H and 5-H), 8.28～9.16 (3H, m, 2-H, 1 '-H and 2 '-H)；MS (m/z): 501 [M+H]+, calculate (C25H23F3N4O4): 500.48.
Embodiment 8
6,8-bis-fluoro-1-(2-fluoro ethyl)-7-(4-thyl-piperazin-1-base)-3-[2-(4-Hydroxy-benzoyIcarbamo)-ethylene-1-base]-quinoline-4 (1H)- Ketone (I-8), its chemical structural formula is:
I.e. Ar in formula I is 4-hydroxy-pheny.
The preparation method of this compound is: substitute aromatic radical ethyl ketone formula VI with 4-hydroxy-acetophenone (0.45g, 3.3mmol), according to The general preparative methods of above-mentioned object formula I, obtains pale yellow crystals object thing (I-8), productivity 56.3%, m.p.161～163 DEG C.1H NMR(400MHz,CD3Cl) δ: 2.36 (3H, s, N-CH3), 2.58～3.47 (8H, m, piperazine-H), 4.76～4.85 (4H, m, FCH2CH2N), 7.76～7.87 (5H, m, Ph-H and 5-H), 8.21～9.06 (3H, m, 2-H, 1 '-H and 2 '-H), 10.55 (1H, brs, OH)；MS (m/z): 472 [M+H]+；Calculate (C25H24F3N3O3): 471.48.
Embodiment 9
6,8-bis-fluoro-1-(2-fluoro ethyl)-7-(4-thyl-piperazin-1-base)-3-[2-(4-pyridine-formoxyl)-ethylene-1-base]-quinoline-4 (1H)- Ketone (I-9), its chemical structural formula is:
I.e. Ar in formula I is 4-pyridine radicals.
The preparation method of this compound is: substitute aromatic radical ethyl ketone formula VI with 4-pyridine-ethyl ketone (0.39g, 3.2mmol), according to upper The general preparative methods of the object formula I stated, obtains pale yellow crystals object thing (I-9), productivity 63.2%, m.p.184～186 DEG C.1H NMR(400MHz,CD3Cl) δ: 2.38 (3H, s, N-CH3), 2.68～3.54 (8H, m, piperazine-H), 4.88～5.06 (4H, m, FCH2CH2N), 8.03 (1H, d, 5-H), 8.33～9.18 (7H, m, 2-H, 1 '-H, 2 '-H and Py-H)； MS (m/z): 457 [M+H]+, calculate (C24H23F3N4O2): 456.47.
Embodiment 10
6,8-bis-fluoro-1-(2-fluoro ethyl)-7-(4-thyl-piperazin-1-base)-3-[2-(4-furan-formyl)-ethylene-1-base]-quinoline-4 (1H)- Ketone (I-10), its chemical structural formula is:
I.e. Ar in formula I is 2-furyl.
The preparation method of this compound is: substitute aromatic radical ethyl ketone formula VI with 2-furan-ethyl ketone (0.42g, 3.8mmol), according to upper The general preparative methods of the object formula I stated, obtains pale yellow crystals object thing (I-10), productivity 65.7%, m.p.174～176 DEG C.1H NMR(400MHz,CD3Cl) δ: 2.36 (3H, s, N-CH3), 2.61～3.53 (8H, m, piperazine-H), 4.85～4.94 (4H, m, FCH2CH2N), 6.83～8.13 (4H, m, 5-H and furan-H), 8.21～9.05 (3H, m, 2-H, 1 '-H and 2’-H)；MS (m/z): 446 [M+H]+, calculate (C23H22F3N3O3): 445.45.
Test example
One, the α of a kind of fleroxacin that embodiment 1-10 provides, the anti tumor activity in vitro of alpha, beta-unsaturated ketone derivant measures
1, test sample
With the α of a kind of fleroxacin that embodiment 1-10 provides, alpha, beta-unsaturated ketone derivant and classical antitumor TOPO inhibitor 10-hydroxycamptothecine (HC) and parent compound fleroxacin (FL) are test sample, and totally 12 kinds, wherein HC and FL is Matched group, embodiment 1-10 sample is experimental group；
Experiment JEG-3 is people's hepatocarcinoma Hep-3B cell, human pancreas cancer Panc-1 cell and human leukemia HL60 cell respectively Strain is all bought from Chinese Academy of Sciences's Shanghai cell bank.Normal cell uses VERO African green monkey kidney cell, buys and sends in upper Cacumen et folium clerodendri mandarinori (Clerodendron mandarinorum Diels) Bio tech ltd.
2, assay method
Concretely comprising the following steps of assay method:
1) first above-mentioned 12 kinds of test samples are dissolved with dimethyl sulfoxide (DMSO) respectively, be configured to 1.0 × 10-2mol·L-1 The storing solution of concentration, dilutes storing solution with the RPMI-1640 culture fluid of the calf serum that mass percent concentration is 10% afterwards Become there are 5 Concentraton gradient (0.1,1.0,5.0,10.0,50.0 μm ol L-1) working solution；
2) take the logarithm people's hepatocarcinoma Hep-3B cell of trophophase, human pancreas cancer Panc-1 cell and human leukemia HL60 cell and VERO cell strain, is inoculated in 96 orifice plates with 6000, every hole cell, and be separately added into above-mentioned 12 kinds of samples subsequently has 5 The working solution of Concentraton gradient, after 48 hours, every hole adds 5g L–1MTT (tetrazolium bromide) solution 10 μ L, continues to be further cultured for 4 hours Add sodium lauryl sulphate (SDS) solution that 100 μ L mass percent concentrations are 10% afterwards.Cultivate 24 hours, then At 570nm wavelength, absorbance (OD) value is measured by microplate reader；
3) test sample of the variable concentrations suppression ratio to cancerous cell is calculated by following shown formula,
Inhibition of cancer cell rate=[(1-experimental group OD value)/matched group OD value] × 100%；
Then with the logarithm value of each concentration of test sample, the inhibition of cancer cell rate that each concentration is corresponding is made linear regression, obtain docs-effect Equation, goes out the test sample half-inhibition concentration (IC to experiment cancerous cell from gained docs-effect Equation for Calculating50)；Each data Parallel assay three times, seeks its meansigma methods, the results are shown in Table shown in 1.
Anti-tumor activity (the IC of each test sample of table 150)
As it can be seen from table 1 the compound that embodiment 1-10 provides is significantly stronger than parent to the inhibitory activity of 3 kinds of cancerous cell of experiment The activity of compound fleroxacin, especially majority of compounds are better than comparison hydroxyl to the growth inhibitory activity of three kinds of experiment cancerous cell The activity of camptothecine, its IC50Value is at or below micro-molar concentration.More meaningful, that embodiment 1-10 provides chemical combination Thing demonstrates relatively low toxicity to VERO cell, has the potentiality of druggability.Therefore, according to the general way of drug development it is First carry out the antitumor in-vitro screening of routine, study the most targetedly, so the compound of the present invention has strong resisting and swells Tumor activity and relatively low toxicity, can be become salt by acid acceptable with human body or be mixed with antitumor drug with pharmaceutical carrier.

Claims (6)

1. a α for fleroxacin, alpha, beta-unsaturated ketone derivant, it is characterised in that there is the general structure of following formula I:
Wherein aromatic rings Ar is phenyl ring or substituted benzene ring or furan nucleus or pyridine ring.
The α of a kind of fleroxacin the most according to claim 1, alpha, beta-unsaturated ketone analog derivative, it is typically characterized by with following The typical compound of structure:
The α of a kind of fleroxacin the most according to claim 1 and 2, the preparation method of alpha, beta-unsaturated ketone derivant, its feature exists In, concrete preparation process includes:
1) with the fleroxacin shown in formula II as raw material, the compound shown in formula III is reacted to obtain through sodium borohydride reduction decarboxylation, so Prepare the compound shown in formula IV afterwards with Ethyl formate condensation reaction, last formula IV and activated manganese dioxide aoxidize to obtain formula V fluorine Luo Sha Star aldehyde:
2) fleroxacin aldehyde shown in formula V and aromatic radical ethyl ketone are formed under the catalysis of alkali α, alpha, beta-unsaturated ketone structure, through after place Reason can obtain the α of a kind of fleroxacin shown in formula I, alpha, beta-unsaturated ketone derivant:
Wherein, the aromatic radical Ar in formula I is phenyl ring or substituted benzene ring or furan nucleus or pyridine ring.
The α of a kind of fleroxacin the most according to claim 3, the preparation method of alpha, beta-unsaturated ketone derivant, it is characterised in that Fleroxacin aldehyde shown in described formula V is 1:1.0～1.2 with the mol ratio of aromatic radical ethyl ketone.
5. as right is required the α of a kind of fleroxacin as described in 1 or 2, and alpha, beta-unsaturated ketone derivant is in preparing antitumor drug Application.
The α of a kind of fleroxacin the most according to claim 5, the application in preparing antitumor drug of the alpha, beta-unsaturated ketone derivant, It is characterized in that, described antitumor drug is treatment hepatocarcinoma, cancer of pancreas or leukemic medicine.
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