CN106279019B - A kind of α of Enrofloxacin, alpha, beta-unsaturated ketone derivative and its preparation method and application - Google Patents
A kind of α of Enrofloxacin, alpha, beta-unsaturated ketone derivative and its preparation method and application Download PDFInfo
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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
- C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- C07D215/54—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3
- C07D215/56—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3 with oxygen atoms in position 4
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- 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
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- 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
Abstract
The invention discloses a kind of α of Enrofloxacin, alpha, beta-unsaturated ketone derivatives and its preparation method and application, using such as I chemical structure of general formula of following formula：
Description
Technical field
The invention belongs to original new drug synthesis technical fields, and in particular to a kind of α of Enrofloxacin, alpha, beta-unsaturated ketone derive
Object, also relates to a kind of α of Enrofloxacin, the preparation method of alpha, beta-unsaturated ketone derivative and its in antitumor drug
Application.
Background technology
Discovery of the new drug innovation originating from primer, and structure-based rational drug MOLECULE DESIGN is to find primer
Effective ways.In the pharmacophore of various structures, there is α, the chalcone compounds of alpha, beta-unsaturated ketone structure feature are as day
Right active ingredient is concerned due to a variety of pharmacological activity.It is taken however, natural chalcone compound is mostly polyhydroxy phenyl ring
The α in generation, beta-unsaturated ketone limit application clinically because its poor water solubility causes bioavilability relatively low.In addition,
Action target spot-topoisomerase in conjunction with antibacterial fluoroquinolone drug is also the important function target spot of antitumor drug, can be by it
Antibacterial activity is converted into antitumor activity, and find fluoquinolone C-3 carboxyls not be pharmacophore necessary to antitumor activity,
It can be replaced with bioisostere to improve its antitumor activity.Based on this it is improved to improve the water solubility of chalcones
Bioavilability and activity, advantage pharmacophore-fluoro- 7- of 1- cyclopropyl -6- of present invention flouroquinolone drugs Ciprofloxacin
(4- ethyl-piperazins)-quinoline -4 (1H) -one skeleton devises novel knot as α, the substituent group of alpha, beta-unsaturated ketone structure
Fluoquinolone " class chalcone " derivative of structure.
For this purpose, the object of the present invention is to provide a kind of α of Enrofloxacin, alpha, beta-unsaturated ketone derivative has antitumor
Effect and effect, while a kind of α of Enrofloxacin, the preparation method of alpha, beta-unsaturated ketone derivative being provided.
In order to achieve the goal above, the technical solution adopted in the present invention is：A kind of α of Enrofloxacin, alpha, beta-unsaturated ketone
Derivative, chemical structural formula is as shown in general formula I：
Ar is phenyl ring or substituted benzene ring or furan nucleus or pyridine ring in formula I, such compound is concrete structure below
Compound：
A kind of α of Enrofloxacin of the present invention, the preparation method of alpha, beta-unsaturated ketone derivative, with En Nuosha shown in formula II
Star is prepared as a raw material,
Specific preparation process is as follows：
1) fluorine quinoline promise shown in formula III is made through restoring the reactions such as decarboxylation, formylated, oxidation in Enrofloxacin shown in formula II
Ketone -3- formaldehyde：
Step 1) is 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.) prodrug grinds
Study carefully synthesis and the antimicrobial acivity of .7.3- formoxyl Carbostyril derivatives) method prepare, detailed process is such as
Under：
2) formaldehyde of fluoquinolone -3- shown in formula III and aryl methyl ketone V are carried out under the catalysis of alkali in absolute ethyl alcohol
After complete reaction target compound shown in formula I is made through handling, reaction process is as follows in aldol reaction：
Wherein, Ar is phenyl ring or substituted benzene ring or furan nucleus or pyridine ring in formula I.
The general operating procedure that is synthetically prepared of target compound shown in formula I is：Take 1- cyclopropyl -6- fluoro- 7- (4- second
Base-piperazine -1- bases)-quinoline -4 (1H) -one -3- formaldehyde (III) 1.0g (3.0mmol) is dissolved in 20mL absolute ethyl alcohols, it is added
Aromatic radical ethyl ketone V (3.0mmol) and base catalyst piperidines (0.1mL).Mixed reactant back flow reaction for 24 hours, places room temperature, filter
Collect the solid generated, absolute ethyl alcohol recrystallization obtains pale yellow crystals object formula I.
As a further improvement, fluoquinolone -3- aldehyde shown in formula III and aromatic radical ethyl ketone formula V mole is 1:1.0
~1.2.
The basic catalyst is at least one of piperidines, pyridine, triethylamine, morpholine, potassium acetate and sodium acetate.
A kind of α of Enrofloxacin, alpha, beta-unsaturated ketone derivative application in preparation of anti-tumor drugs.
The antitumor drug is treatment liver cancer, cancer of pancreas or leukemia medicament.
A kind of α of Enrofloxacin of the present invention, principle of hybridization of the alpha, beta-unsaturated ketone derivative based on pharmacophore, by fluorine quinoline promise
Ketone skeleton and α, alpha, beta-unsaturated ketone pharmacophore are effectively combined, and design has synthesized the α of Enrofloxacin, alpha, beta-unsaturated ketone derivative,
The complementation and active superposition for realizing different structure pharmacophore can be used as completely new knot to achieve synergistic and detoxifying effects
The antitumor drug of structure is developed.
Specific implementation mode
Embodiment 1
The fluoro- 7- of 1- cyclopropyl -6- (4- ethyl-piperazin -1- bases) -3- (2- benzoyls-ethylene -1- bases)-quinoline -4 (1H) -
Ketone (I-1), chemical structural formula are：
Ar i.e. in formula I is phenyl.
The preparation method of the compound is：Aryl methyl ketone formula V is substituted with acetophenone (0.43g, 3.6mmol), according to above-mentioned
Object formula I general preparative methods, obtain pale yellow crystals object (I-1), yield 62.6%, m.p.132~134 DEG C.1H NMR(400MHz,CD3Cl)δ：1.17~1.34 (7H, m, cyclopropyl-H and CH3), 2.26 (2H, q, CH2), 2.83~3.36
(8H, m, piperazine-H), 3.68 (1H, m, cyclopropyl-H), 6.76~7.68 (6H, m, Ph-H and 8-H), 7.87 (1H, d, 5-H),
8.05~the 8.73 (- H of 3H, m, 1 ', 2 '-H and 2-H)；MS(m/z)：446[M+H]+, calculate (C27H28FN3O2)：445.54.Implement
Example 2
The fluoro- 7- of 1- cyclopropyl -6- (4- ethyl-piperazin -1- bases) -3- [2- (4- methoxybenzoyls)-ethylene -1- bases] -
Quinoline -4 (1H) -one (I-2), chemical structural formula are：
Ar i.e. in Formulas I is p-methoxyphenyl.
The preparation method of the compound is：Aryl methyl ketone formula is substituted with 4- methoxy-acetophenones (0.45g, 3.0mmol)
V, according to the general preparative methods of above-mentioned object formula I, obtain pale yellow crystals object (I-2), yield 73.4%,
M.p.134~136 DEG C.1H NMR(400MHz,CD3Cl)δ：1.16~1.35 (7H, m, cyclopropyl-H and CH3), 2.24 (2H, q,
CH2), 2.86~3.35 (8H, m, piperazine-H), 3.66 (1H, m, cyclopropyl-H), 3.87 (3H, s, OCH3), 7.52~7.83
(5H, m, Ph-H and 8-H), 8.07 (1H, d, 5-H), 8.13~the 8.84 (- H of 3H, m, 1 ', 2 '-H and 2-H)；MS(m/z)：476[M
+H]+；Calculate (C28H30FN3O3)：475.57.
Embodiment 3
The fluoro- 7- of 1- cyclopropyl -6- (4- ethyl-piperazin -1- bases) -3- [2- (3,4- dioxymethylenes-benzoyl)-ethylene -
1- yls]-quinoline -4 (1H) -one (I-3), chemical structural formula is：
Ar i.e. in formula I is 3,4- (dioxymethylene) phenyl.
The preparation method of the compound is：Aryl second is substituted with 3,4- dioxymethylenes-acetophenone (0.49g, 3.0mmol)
Keto-acid V obtains pale yellow crystals object object (I-3), yield according to the general preparative methods of above-mentioned object formula I
68.7%, m.p.161~163 DEG C.1H NMR(400MHz,CD3Cl)δ:1.18~1.37 (7H, m, cyclopropyl-H and CH3),
2.27 (2H, q, CH2), 2.88~3.37 (8H, m, piperazine-H), 3.68 (1H, m, cyclopropyl-H), 6.22 (2H, s, OCH2O),
7.63~7.85 (4H, m, Ph-H and 8-H), 8.08 (1H, d, 5-H), 8.16~the 8.87 (- H of 3H, m, 1 ', 2 '-H and 2-H)；MS
(m/z)：490[M+H]+, calculate (C28H28FN3O4)：489.55.
Embodiment 4
The fluoro- 7- of 1- cyclopropyl -6- (4- ethyl-piperazin -1- bases) -3- [2- (3,4,5- trimethoxies methyl-benzoyl)-second
Alkene -1- bases]-quinoline -4 (1H) -one (I-4), chemical structural formula is：
Ar i.e. in Formulas I is 3,4,5- 2,4,5-trimethoxyphenyls.
The preparation method of the compound is：With 3,4,5- trimethoxies-acetophenone (0.63g, 3.0mmol) substitutes aryl second
Keto-acid V obtains pale yellow crystals object object (I-4), yield according to the general preparative methods of above-mentioned object formula I
61.5%, m.p.144~146 DEG C.1H NMR(400MHz,CD3Cl)δ:1.17~1.36 (7H, m, cyclopropyl-H and CH3),
2.26 (2H, q, CH2), 3.13~3.42 (8H, m, piperazine-H), 3.68 (1H, m, cyclopropyl-H), 3.88,3.93 (9H, 2s, 3
×OCH3), 7.66~7.87 (3H, m, Ph-H and 8-H), 8.12 (1H, d, 5-H), 8.23~8.88 (- the H of 3H, m, 1 ', 2 '-H and
2-H)；MS(m/z)：536[M+H]+, calculate (C30H34FN3O5)：535.62.
Embodiment 5
The fluoro- 7- of 1- cyclopropyl -6- (4- ethyl-piperazin -1- bases) -3- [2- (4- methyl-benzoyls)-ethylene -1- bases]-quinoline
Quinoline -4 (1H) -one (I-5), chemical structural formula are：
Ar i.e. in formula I is to methylphenyl.
The preparation method of the compound is：Aryl methyl ketone formula V is substituted with 4- methyl-acetophenones (0.44g, 3.3mmol),
According to the general preparative methods of above-mentioned object formula I, pale yellow crystals object object (I-5), yield 537%, m.p.131 are obtained
~133 DEG C.1H NMR(400MHz,CD3Cl)δ:1.14~1.35 (7H, m, cyclopropyl-H and CH3), 2.23~2.27 (5H, m,
Ph-CH3And CH2), 2.62~3.37 (8H, m, piperazine-H), 3.65 (1H, m, cyclopropyl-H), 7.43~7.76 (5H, m, Ph-H
And 8-H), 7.96 (1H, d, 5-H), 8.04 (1H, s, 2-H), 8.16, the 8.78 (- H of 2H, 2d, 1 ' and 2 '-H)；MS(m/z)：460
[M+H]+, calculate (C28H30FN3O2)：459.57.
Embodiment 6
The fluoro- 7- of 1- cyclopropyl -6- (4- ethyl-piperazin -1- bases) -3- [2- (the fluoro- benzoyls of 4-)-ethylene -1- bases]-quinoline
Quinoline -4 (1H) -one (I-6), chemical structural formula are：
Ar i.e. in formula I is to fluoro-phenyl.
The preparation method of the compound is：Aryl methyl ketone formula V is substituted with the fluoro- acetophenones of 4- (0.50g, 3.6mmol), according to
According to the general preparative methods of above-mentioned object formula I, pale yellow crystals object object (I-6), yield 65.2%, m.p.155 are obtained
~157 DEG C.1H NMR(400MHz,CD3Cl)δ:1.22~1.43 (7H, m, cyclopropyl-H and CH3), 2.32 (2H, q, CH2),
3.15~3.46 (8H, m, piperazine-H), 3.75 (1H, m, cyclopropyl-H), 7.76~7.87 (5H, m, Ph-H and 8-H), 8.13
(1H, d, 5-H), 8.18~the 8.89 (- H of 3H, m, 1 ', 2 '-H and 2-H)；MS(m/z)：464[M+H]+, calculate (C27H27F2N3O2)：
463.53。
Embodiment 7
The fluoro- 7- of 1- cyclopropyl -6- (4- ethyl-piperazin -1- bases) -3- [2- (4- nitro-benzoyls)-ethylene -1- bases]-quinoline
Quinoline -4 (1H) -one (I-7), chemical structural formula are：
Ar i.e. in formula I is p-nitrophenyl.
The preparation method of the compound is：Aryl methyl ketone formula V is substituted with 4- nitro-acetophenones (0.50g, 3.0mmol),
According to the general preparative methods of above-mentioned object formula I, pale yellow crystals object object (I-7) is obtained, yield 62.8%,
M.p.168~170 DEG C.1H NMR(400MHz,CD3Cl)δ:1.26~1.45 (7H, m, cyclopropyl-H and CH3), 2.34 (2H, q,
CH2), 3.18~3.53 (8H, m, piperazine-H), 3.76 (1H, m, cyclopropyl-H), 7.82~8.11 (5H, m, Ph-H and 8-H),
8.22 (1H, d, 5-H), 8.25~the 9.13 (- H of 3H, m, 1 ', 2 '-H and 2-H)；MS(m/z)：491[M+H]+, calculate
(C27H27FN4O4)：490.54.
Embodiment 8
The fluoro- 7- of 1- cyclopropyl -6- (4- ethyl-piperazin -1- bases) -3- [2- (4- Hydroxy-benzoyIcarbamos)-ethylene -1- bases]-quinoline
Quinoline -4 (1H) -one (I-8), chemical structural formula are：
Ar i.e. in formula I is 4- hydroxy-phenies.
The preparation method of the compound is：Aryl methyl ketone V is substituted with 4- hydroxy-acetophenones (0.45g, 3.3mmol), according to
According to the general preparative methods of above-mentioned object formula I, pale yellow crystals object object (I-8), yield 46.8%, m.p.156 are obtained
~158 DEG C.1H NMR(400MHz,CD3Cl)δ:1.17~1.36 (7H, m, cyclopropyl-H and CH3), 2.25 (2H, q, CH2),
2.67~3.36 (8H, m, piperazine-H), 3.65 (1H, m, cyclopropyl-H), 7.62~7.83 (5H, m, Ph-H and 8-H), 8.02
(1H, d, 5-H), 8.18~the 8.87 (- H of 3H, m, 1 ', 2 '-H and 2-H), 10.53 (1H, s, OH)；MS(m/z)：462[M+H]+,
Calculate (C27H28FN3O3)：461.54.
Embodiment 9
The fluoro- 7- of 1- cyclopropyl -6- (4- ethyl-piperazin -1- bases) -3- [2- (4- pyridines-formoxyl)-ethylene -1- bases]-quinoline
Quinoline -4 (1H) -one (I-9), chemical structural formula are：
Ar i.e. in formula I is 4- pyridyl groups.
The preparation method of the compound is：Aryl methyl ketone formula V is substituted with 4- pyridines-ethyl ketone (0.36g, 3.0mmol), according to
According to the general preparative methods of above-mentioned object formula I, pale yellow crystals object object (I-9), yield 58.6%, m.p.174 are obtained
~176 DEG C.1H NMR(400MHz,CD3Cl)δ:1.28~1.47 (7H, m, cyclopropyl-H and CH3), 2.36 (2H, q, CH2),
3.23~3.65 (8H, m, piperazine-H), 3.78 (1H, m, cyclopropyl-H), 7.88 (1H, d, 8-H), 8.26~9.17 (7H, m,
1 '-H, 2 '-H, 2-H and Py-H)；MS(m/z)：447[M+H]+, calculate (C26H27FN4O2)：446.53.
Embodiment 10
The fluoro- 7- of 1- cyclopropyl -6- (4- ethyl-piperazin -1- bases) -3- [2- (4- furans-formyl)-ethylene -1- bases]-quinoline
Quinoline -4 (1H) -one (I-10), chemical structural formula are：
Ar i.e. in formula I is 2- furyls.
The preparation method of the compound is：Aryl methyl ketone formula V is substituted with 2- furans-ethyl ketone (0.40g, 3.6mmol), according to
According to the general preparative methods of above-mentioned object formula I, pale yellow crystals object object (I-10), yield 51.6%, m.p.168 are obtained
~168 DEG C.1H NMR(400MHz,CD3Cl)δ:1.23~1.45 (7H, m, cyclopropyl-H and CH3), 2.32 (2H, q, CH2),
3.17~3.62 (8H, m, piperazine-H), 3.76 (1H, m, cyclopropyl-H), 6.82~7.78 (4H, m, furans-H and 8-H), 8.13
(1H, d, 5-H), 8.22~the 9.13 (- H of 3H, m, 1 ', 2 '-H and 2-H)；MS(m/z)：436[M+H]+, calculate (C25H26FN3O3)：
435.50。
Test example
One, the anti tumor activity in vitro of the α for a kind of Enrofloxacin that embodiment 1-10 is provided, alpha, beta-unsaturated ketone derivative are surveyed
It is fixed
1, test sample
With a kind of α of the embodiment 1-10 Enrofloxacins provided, alpha, beta-unsaturated ketone derivative and classical antitumor TOPO suppressions
Preparation 10-hydroxycamptothecine (HC) and parent compound Enrofloxacin (EN) are test sample, and totally 12 kinds, wherein HC and EN 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；
2) the human liver cancer Hep-3B cells, human pancreas cancer Panc-1 cells and human leukemia HL60 cells of logarithmic growth phase
And VERO cell strains are then separately added into the dense with 5 of above-mentioned 12 kinds of samples with 6000, every hole cell inoculation in 96 orifice plates
5gL is added in the working solution for spending gradient per hole after 48 hours–110 μ L of MTT (tetrazolium bromide) solution, continue to be further cultured for after 4 hours
Lauryl sodium sulfate (SDS) solution that 100 μ L mass percent concentrations are 10% is added.Culture 24 hours, then with enzyme mark
Instrument measures absorbance (OD) value at 570nm 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 growth inhibitory activity of the activity of parent compound Enrofloxacin, especially majority of compounds to human pancreas cancer Panc-1 cells
It is better than the activity of control hydroxycamptothecin, IC50Value has reached or is less than micro-molar concentration.What makes more sense is that embodiment 1-10
The compound of offer shows low toxicity VERO cells, the potentiality with druggability.Therefore, according to the one of drug development
As approach be first to carry out conventional antitumor in-vitro screening, then targetedly studied, thus the compound of the present invention have
There are strong antitumor activity and lower toxicity, it can be anti-by being mixed with acid human-acceptable at salt or with pharmaceutical carrier
Tumour medicine.
Claims (5)
1. a kind of α of Enrofloxacin, alpha, beta-unsaturated ketone derivative are typically characterized by as with the typical compound of lower structure：
2. a kind of α of Enrofloxacin according to claim 1, the preparation method of alpha, beta-unsaturated ketone derivative, feature exist
In specific preparation process includes：
1) using Enrofloxacin shown in formula II as raw material, be reduced by sodium borohydride and then decarboxylated, formylated, oxidation reaction be made III institute of formula
Fluoquinolone -3- the formaldehyde shown：
2) fluoquinolone -3- formaldehyde shown in formula III and aromatic radical ethyl ketone are formed into α, alpha, beta-unsaturated ketone knot under the catalysis of alkali
Structure, it is post-treated to be prepared into a kind of α of Enrofloxacin, alpha, beta-unsaturated ketone derivative shown in claim 1.
3. a kind of α of Enrofloxacin according to claim 2, the preparation method of alpha, beta-unsaturated ketone derivative, feature exist
In：The molar ratio of fluoquinolone -3- formaldehyde shown in formula III and aromatic radical ethyl ketone is 1:1.0~1.2.
4. a kind of α of Enrofloxacin as described in claim 1, alpha, beta-unsaturated ketone derivative answering in the preparation of antitumor drugs
With.
5. a kind of α of Enrofloxacin according to claim 4, alpha, beta-unsaturated ketone derivative is in the preparation of antitumor drugs
Using, which is characterized in that the antitumor drug is the drug for treating liver cancer, cancer of pancreas or leukaemia.
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| CN112824407A (en) * | 2019-11-20 | 2021-05-21 | 河南大学 | N-methylmoxifloxacin propenone derivative and preparation method and application thereof |
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| CN101400655A (en) * | 2006-03-16 | 2009-04-01 | 安斯泰来制药有限公司 | Quinolone derivative or pharmaceutically acceptable salt thereof |
| CN104557973A (en) * | 2014-12-23 | 2015-04-29 | 河南大学 | 3,3'-methene-difluoroquinolone derivative of chiral oxazine quinoline ring as well as preparation method and application of 3,3'-methene-difluoroquinolone derivative |
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| US8889874B2 (en) * | 2010-01-12 | 2014-11-18 | Council Of Scientific And Industrial Research | Imidazolone-chalcone derivatives as potential anticancer agent and process for the preparation thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101400655A (en) * | 2006-03-16 | 2009-04-01 | 安斯泰来制药有限公司 | Quinolone derivative or pharmaceutically acceptable salt thereof |
| CN104557973A (en) * | 2014-12-23 | 2015-04-29 | 河南大学 | 3,3'-methene-difluoroquinolone derivative of chiral oxazine quinoline ring as well as preparation method and application of 3,3'-methene-difluoroquinolone derivative |
Non-Patent Citations (1)
| Title |
|---|
| 二氢氟喹诺酮查尔酮衍生物的合成及抗肿瘤活性研究;仵钊锋;《中国优秀硕士学位论文全文数据库 医药卫生科技辑》;20150415(第4期);E079-2 * |
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