CN106317083A - Alpha, beta-unsaturated ketone derivative of rufloxacin, preparation method of derivative, and application of derivative - Google Patents
Alpha, beta-unsaturated ketone derivative of rufloxacin, preparation method of derivative, and application of derivative Download PDFInfo
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- YQMKCJGJWQUADQ-QPJJXVBHSA-N CN(CC1)CCN1c(c(SCC1)c(c2c3)N1C=C(/C=C/C(c(cc1)ccc1[N+]([O-])=O)=O)C2=O)c3F Chemical compound CN(CC1)CCN1c(c(SCC1)c(c2c3)N1C=C(/C=C/C(c(cc1)ccc1[N+]([O-])=O)=O)C2=O)c3F YQMKCJGJWQUADQ-QPJJXVBHSA-N 0.000 description 1
- SJBOXUKHUIBDTH-BQYQJAHWSA-N Cc(cc1)ccc1C(/C=C/C1=CN(CCSc2c(c(F)c3)N4CCN(C)CC4)c2c3C1=O)=O Chemical compound Cc(cc1)ccc1C(/C=C/C1=CN(CCSc2c(c(F)c3)N4CCN(C)CC4)c2c3C1=O)=O SJBOXUKHUIBDTH-BQYQJAHWSA-N 0.000 description 1
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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 an alpha, beta-unsaturated ketone derivative of rufloxacin, a preparation method of the derivative, and an application of the derivative. The chemical structure of the derivative is represented by formula I shown in the description; and in the formula I, aromatic nucleus Ar is a phenyl ring or a substituted phenyl ring or a furan ring or a pyridine ring. The alpha, beta-unsaturated ketone derivative of rufloxacin realizes effective merging of a ciprofloquinolone skeleton and an alpha, beta-unsaturated ketone skeleton in order to construct a new fluoroquinolone "chalcone-like" compound, so the antitumor activity of the new compound is increased, the toxic and side effects on normal cells are reduced, and the compound can be used as an antitumor active substance to develop antitumor medicines with a brand new structure.
Description
Technical field
The invention belongs to original new drug synthesis technical field, be specifically related to the α of a kind of rufloxacin, alpha, beta-unsaturated ketone derivant, with
Time further relate to the α of a kind of rufloxacin, 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 its bioisostere to improve its anti-tumor activity.Based on this, for improving the water solublity of chalcones, improve it
Bioavailability and activity, the present invention advantage pharmacophore thiazine of flouroquinolone drugs rufloxacin quinoline-4 (1H)-one bone
Frame is as α, the substituent group of alpha, beta-unsaturated ketone structure, and then devises 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 rufloxacin, alpha, beta-unsaturated ketone derivant, have antineoplastic action and
Effect, provides the α of a kind of rufloxacin, 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 rufloxacin, 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 rufloxacin of the present invention, the preparation method of alpha, beta-unsaturated ketone derivant, is former with the rufloxacin 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 rufloxacin 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 rufloxacin 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) rufloxacin aldehyde shown in formula V and aromatic radical ethyl ketone VI are carried out aldol condensation under base catalysis in dehydrated alcohol anti-
Should, after question response is complete, the treated target compound that obtains is as shown in formula I, and detailed process is as follows:
In formula I, Ar is phenyl ring or substituted benzene ring or furan nucleus or pyridine ring.
Step 2) the general synthetically prepared operating procedure of target compound formula I is: take 1,8-(3,1-sulfur ethyl)-6-fluoro-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 IV (3.2mmol) and base catalyst piperidines (0.1mL).Mixed reactant back flow reaction 24h, places room temperature,
The solid that filter collection produces, dehydrated alcohol recrystallization, obtain pale yellow crystals target compound thing formula I.
As further improving, the rufloxacin aldehyde shown in formula V and Formula IV aromatic radical ethyl ketone mole are 1:1.0～1.2.
Described base catalyst is at least one in piperidines, pyridine, triethylamine, morpholine, potassium acetate and sodium acetate.
The α of described a kind of rufloxacin, 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 rufloxacin of the present invention, alpha, beta-unsaturated ketone derivant principle of hybridization based on pharmacophore, by fluoroquinolone skeleton
With α, alpha, beta-unsaturated ketone pharmacophore is effectively combined, and design has synthesized the α of rufloxacin, alpha, beta-unsaturated ketone derivant, it is achieved that
The complementation of different structure pharmacophore and the superposition of activity, thus reached the effect of potentiation toxicity reduction, can swell as the anti-of brand new
Tumor medicine is developed.
Detailed description of the invention
Embodiment 1
1,8-(3,1-sulfur ethyl) fluoro-7-of-6-(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 Formula IV with 1-Phenylethanone. (0.45g, 3.8mmol), according to above-mentioned
The general preparative methods of object formula I, obtains pale yellow crystals object (I-1), productivity 63.6%, m.p.153～155 DEG C.1H NMR
(400MHz,CD3Cl) δ: 2.32 (3H, s, N-CH3), 3.12～3.47 (10H, m, piperazine-H and thiazine-H), 4.72 (2H,
T, thiazine-H), 7.55～7.87 (6H, m, Ph-H and 5-H), 8.20～8.91 (3H, m, 2-H, 1 '-H and 2 '-H)；MS (m/z):
450[M+H]+, calculate (C25H24FN3O2S): 449.55.
Embodiment 2
1,8-(3,1-sulfur ethyl) fluoro-7-of-6-(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 IV 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 65.8%, m.p.
155～157 DEG C.1H NMR(400MHz,CD3Cl) δ: 2.34 (3H, s, N-CH3), 3.15～3.48 (10H, m, piperazines
-H and thiazine-H), 3.87 (3H, s, OCH3), 4.74 (2H, t, thiazine-H), 7.62～7.88 (5H, m, Ph-H and 5-H),
8.23～8.92 (3H, m, 2-H, 1 '-H and 2 '-H)；MS (m/z): 480 [M+H]+, calculate (C26H26FN3O3S): 479.58.
Embodiment 3
1,8-(3,1-sulfur ethyl) fluoro-7-of-6-(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 Formulas 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, obtains pale yellow crystals object thing (I-3), productivity 72.6%, m.p.
172～174 DEG C.1H NMR(400MHz,CD3Cl) δ: 2.36 (3H, s, N-CH3), 3.17～3.52 (10H, m, piperazines
-H and thiazine-H), 4.76 (2H, t, thiazine-H), 6.28 (3H, s, OCH2O), 7.67～7.93 (4H, m, Ph-H and 5-H),
8.24～8.95 (3H, m, 2-H, 1 '-H and 2 '-H)；MS (m/z): 494 [M+H]+, calculate (C26H24FN3O4S): 493.56.
Embodiment 4
1,8-(3,1-sulfur ethyl) fluoro-7-of-6-(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 IV, according to the general preparative methods of above-mentioned object formula I, obtains pale yellow crystals object thing (I-4), productivity 67.2%,
M.p.151～153 DEG C.1H NMR(400MHz,CD3Cl) δ: 2.35 (3H, s, N-CH3), 3.18～3.55 (10H, m,
Piperazine-H and thiazine-H), 4.78 (2H, t, thiazine-H), 3.87,3.89 (9H, 2s, 3 × OCH3), 7.75～8.13 (3H, m,
Ph-H and 5-H), 8.28～8.93 (3H, m, 2-H, 1 '-H and 2 '-H)；MS (m/z): 540 [M+H]+, calculate (C28H30FN3O5S):
539.63。
Embodiment 5
1,8-(3,1-sulfur ethyl) fluoro-7-of-6-(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 IV 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 53.8%, m.p.
136～138 DEG C.1H NMR(400MHz,CD3Cl) δ: 2.25,2.32 (6H, 2s, 2s, Ph-CH3And N-CH3), 3.13～3.46
(10H, m, piperazine-H and thiazine-H), 4.72 (2H, t, thiazine-H), 7.56～7.81 (5H, m, Ph-H and 5-H), 8.18～8.91
(3H, m, 2-H, 1 '-H and 2 '-H)；MS (m/z): 464 [M+H]+, calculate (C26H26FN3O2S): 463.58.
Embodiment 6
1,8-(3,1-sulfur ethyl) fluoro-7-of-6-(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 IV 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 73.5%, m.p.163～165 DEG C.1H NMR(400MHz,CD3Cl) δ: 2.36 (3H, s, N-CH3), 3.17～3.52 (10H, m, piperazine-H and thiazine-H),
(4.76 2H, t, thiazine-H), 7.73～7.94 (5H, m, Ph-H and 5-H), 8.25～8.94 (3H, m, 2-H, 1 '-H and 2 '-H)；
MS (m/z): 468 [M+H]+, calculate (C25H23F2N3O2S): 467.54.
Embodiment 7
1,8-(3,1-sulfur ethyl) fluoro-7-of-6-(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 IV with 4-nitro-acetophenone (0.53g, 3.2mmol), according to
The general preparative methods of above-mentioned object I, obtains pale yellow crystals object thing (I-7), productivity 74.5%, m.p.168～170 DEG C.1H NMR(400MHz,CD3Cl) δ: 2.42 (3H, s, N-CH3), 3.23～3.61 (8H, m, piperazine-H), 4.78 (2H,
T, thiazine-H), 7.82～7.96 (5H, m, Ph-H and 5-H), 8.27～9.12 (3H, m, 2-H, 1 '-H and 2 '-H)；MS
(m/z): 495 [M+H]+, calculate (C25H23FN4O4S): 494.55.
Embodiment 8
1,8-(3,1-sulfur ethyl) fluoro-7-of-6-(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 IV 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 51.8%, m.p.
155～157 DEG C.1H NMR(400MHz,CD3Cl) δ: 2.37 (3H, s, N-CH3), 3.21～3.58 (8H, m, piperazine-H),
4.77 (2H, t, thiazine-H), 7.76～7.87 (5H, m, Ph-H and 5-H), 8.21～9.06 (3H, m, 2-H, 1 '-H and 2 '-H),
10.57 (1H, brs, OH)；MS (m/z): 466 [M+H]+, calculate (C25H24FN3O3S): 465.55.
Embodiment 9
1,8-(3,1-sulfur ethyl) fluoro-7-of-6-(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 IV 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 58.2%, m.p.183～185 DEG C.1H NMR(400MHz,CD3Cl) δ: 2.38 (3H, s, N-CH3), 3.25～3.66 (8H, m, piperazine-H), 4.82 (2H,
T, thiazine-H), 7.86 (1H, d, 5-H), 8.30～9.17 (7H, m, 2-H, 1 '-H, 2 '-H and Py-H)；MS (m/z):
451[M+H]+, calculate (C24H23FN4O2S): 450.54.
Embodiment 10
1,8-(3,1-sulfur ethyl) fluoro-7-of-6-(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 IV 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 63.4%, m.p.167～169 DEG C.1H NMR(400MHz,CD3Cl) δ: 2.38 (3H, s, N-CH3), 3.25～3.62 (8H, m, piperazine-H), 4.80 (2H,
T, thiazine-H), 6.85～7.88 (4H, m, 5-H and furan-H), 8.17～8.93 (3H, m, 2-H, 1 '-H and 2 '-H)；
MS (m/z): 440 [M+H]+, calculate (C23H22FN3O3S): 439.51.
Test example
One, the α of a kind of rufloxacin 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 rufloxacin that embodiment 1-10 provides, alpha, beta-unsaturated ketone derivant and classical antitumor TOPO inhibitor
10-hydroxycamptothecine (HC) and parent compound rufloxacin (LF) are test sample, and totally 12 kinds, wherein HC and LF 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 rufloxacin (LF), especially majority of compounds are strong to the growth inhibitory activity of human pancreas cancer Panc-1 cell
In the activity of comparison hydroxycamptothecin, its IC50Value is at or below micro-molar concentration.More meaningful, embodiment 1-10 carries
The compound of confession demonstrates relatively low toxicity to VERO cell, has the potentiality of druggability.Therefore, according to the one of drug development
As approach be first carry out routine antitumor in-vitro screening, study the most targetedly, so the compound of the present invention has
Strong anti-tumor activity and relatively low toxicity, can be become salt by acid acceptable with human body or be mixed with antitumor with pharmaceutical carrier
Medicine.
Claims (6)
1. a α for rufloxacin, alpha, beta-unsaturated ketone derivant, it is characterised in that there is the general structure of following formula I:
In formula I, aromatic rings Ar is phenyl ring or substituted benzene ring or furan nucleus or pyridine ring.
The α of a kind of rufloxacin 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 rufloxacin 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 rufloxacin shown in formula II as raw material, the compound shown in formula III is prepared through the reaction of sodium borohydride reduction decarboxylation,
Then the compound shown in formula IV is prepared with Ethyl formate condensation reaction；Last formula IV prepares formula V reed with activated manganese dioxide oxidation
Flucloxacillin aldehyde:
2) rufloxacin 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 rufloxacin 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 rufloxacin the most according to claim 3, the preparation method of alpha, beta-unsaturated ketone derivant, it is characterised in that
Rufloxacin 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 rufloxacin as described in 1 or 2, and alpha, beta-unsaturated ketone derivant is in preparing antitumor drug
Application.
The α of a kind of rufloxacin 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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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1087639A (en) * | 1992-01-27 | 1994-06-08 | 藤泽药品工业株式会社 | Heterotricyclic derivatives |
| US20020103170A1 (en) * | 2000-07-12 | 2002-08-01 | Turner Steven Ronald | Oxazinoquinolones useful for the treatment of viral infections |
| CN102827187A (en) * | 2012-07-18 | 2012-12-19 | 河南大学 | Fluoroquinolone acetal isoniazone, and preparation method and application thereof |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1087639A (en) * | 1992-01-27 | 1994-06-08 | 藤泽药品工业株式会社 | Heterotricyclic derivatives |
| US20020103170A1 (en) * | 2000-07-12 | 2002-08-01 | Turner Steven Ronald | Oxazinoquinolones useful for the treatment of viral infections |
| CN102827187A (en) * | 2012-07-18 | 2012-12-19 | 河南大学 | Fluoroquinolone acetal isoniazone, and preparation method and application thereof |
Non-Patent Citations (1)
| Title |
|---|
| 王新: "氟喹诺酮酰腙的合成与活性研究", 《中国优秀硕士学位论文全文数据库 医药卫生科技辑》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111303189A (en) * | 2019-11-19 | 2020-06-19 | 郑州工业应用技术学院 | Propenone derivative of rufloxacin, and preparation method and application thereof |
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| CN106317083B (en) | 2018-08-31 |
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