CN102827223A - Di-pyrimidine base tricyclic nucleoside compound, and synthetics method and pharmaceutical use thereof - Google Patents
Di-pyrimidine base tricyclic nucleoside compound, and synthetics method and pharmaceutical use thereof Download PDFInfo
- Publication number
- CN102827223A CN102827223A CN201210333899XA CN201210333899A CN102827223A CN 102827223 A CN102827223 A CN 102827223A CN 201210333899X A CN201210333899X A CN 201210333899XA CN 201210333899 A CN201210333899 A CN 201210333899A CN 102827223 A CN102827223 A CN 102827223A
- Authority
- CN
- China
- Prior art keywords
- tricyclic
- anhydrous
- compound
- nucleoside prodrugs
- compound base
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a di-pyrimidine base tricyclic nucleoside compound, and a synthetics method and the pharmaceutical use of the di-pyrimidine base tricyclic nucleoside compounds, belonging to the field of pharmaceutical chemistry. The di-pyrimidine base tricyclic nucleoside compound has the following structural general formula, wherein when R1 is OH, R2 is selected from H, F, Cl, Br, I and CH3; and when R1 is NH2, R2 is selected form H and F. The compound synthesized by the invention has better antineoplastic activity, and the synthetics method is simple and feasible, and higher in yield, and provides a screening drug for the development of the novel antitumor drug.
Description
Technical field
The present invention relates to one type of new type double pyrimidine bases Tricyclic-nucleoside compounds, its compound method and pharmaceutical use, belong to the pharmaceutical chemistry field.
Background technology
Tumour is the healthy common disease of a kind of serious harm people, and especially malignant tumour has sickness rate height, characteristics that mortality ratio is high.The tumor treatment method has operative treatment, radiotherapy and pharmacological agent (chemotherapy).At present, chemotherapy is still the main means of clinical treatment broad variety malignant tumour.Therefore, seek the vital task that new chemotherapeutic agent is the treatment malignant tumour.
Nucleoside compound is the big emphatically effect of performance in the antineoplaston field, and many antitumor drugs of present clinical use belong to nucleoside compound, for example cytosine arabinoside, gemcitabine and capecitabine etc.Nucleoside compound generally is made up of glycosyl part and base portion, respectively glycosyl part and base portion is modified transformation, just can synthesize multiple nucleoside compound, and then studies the biological activity of this compounds.
The inventor in 2003 synthesize a kind of five acetylize C10 higher carbon sugars (Liu Hongmin, Zou Dapeng, Liu Zhenzhong, C10 higher carbon sugar and verivate thereof, Preparation method and use, CN1523030A).The contriver further recognizes the dipolymer (expression formula 1) of the similar of five acetylize C10 higher carbon sugars in bimolecular 5-ribodesose; The double alkali yl Tricyclic-nucleoside structure that is formed by the C10 higher carbon sugar then is similar to the dipolymer (expression formula 2) of bimolecular 5 '-deoxynucleoside; And 5 '-deoxynucleoside compounds; For example Furtulon and capecitabine all are the antitumor drugs of clinical use, thereby the nucleosides that is formed by the C10 higher carbon sugar has reasonable antitumor action.For this reason, the present invention has carried out the synthetic and activity test of a series of new compounds.Do not see the pertinent literature report at present.
Expression formula 1
Expression formula 2.
Summary of the invention
For the exploitation of new type antineoplastic medicine provides screening of medicaments, the object of the invention is to provide one type of new type double pyrimidine bases Tricyclic-nucleoside compounds; Another purpose is to provide its compound method and medicinal application.
For realizing the object of the invention, technical scheme of the present invention is following:
One type of Sulfadiazine Compound base tricyclic-nucleoside prodrugs of the present invention has following general structure:
R wherein
1During for OH, R
2Be selected from H, F, Cl, Br, I or CH
3R
1Be NH
2The time, R
2Be selected from H, F.
Another kind of Sulfadiazine Compound base tricyclic-nucleoside prodrugs has following general structure:
R wherein
1During for OH, R
2Be selected from H, F, Cl, Br, I or CH
3R
1Be NH
2The time, R
2Be selected from H, F.
Preparation Sulfadiazine Compound base tricyclic-nucleoside prodrugs
2a-2hMethod, it is characterized in that, in the organic solvent, compound
1React under the effect of catalyzer with the pyrimidine of trimethyl silicon based protection, obtain compound
2a-2hPyrimidine is selected from uridylic, 5 FU 5 fluorouracil, 5-chlorouracil, 5-bromouracil, 5-iodouracil, thymus pyrimidine, 5-flurocytosine or cytosine(Cyt).Catalyzer is selected from Zinc Chloride Anhydrous, anhydrous boron trifluoride, anhydrous stannic chloride, trimethylammonium silication triflate or anhydrous titanium tetrachloride.Used organic solvent is selected from anhydrous acetonitrile, anhydrous 1,2-ethylene dichloride, anhydrous methylene chloride, anhydrous tetrahydro furan or anhydrous diethyl ether.
Preparation Sulfadiazine Compound base tricyclic-nucleoside prodrugs
3a-3hMethod, it is characterized in that, in the solvent, compound
2a-2hDeacetylate obtains compound under the effect of alkali
3a-3hAlkali is selected from yellow soda ash, salt of wormwood, sodium hydrogencarbonate, sodium hydroxide, Pottasium Hydroxide, ammonia.Said solvent selects methyl alcohol, ethanol or water.
With synthetic Sulfadiazine Compound base tricyclic-nucleoside prodrugs of the present invention
3a-3hBe used for preparing antitumor drug.Adopt four tetrazolium bromides (MTT) method assessing compound
3a-3hTo Ec9706, Ec109, MGC-803, PC-3 and S180 five strain tumor cell proliferation inhibition effects, measure compound then
3a-3h existsAnti-tumor in vivo in the transplantability mouse S180 sarcoma model is active.
Synthetic compound of the present invention has better antitumor activity, and its spinoff is less; Raw material is simple and easy to, the compound method simple possible, and yield is higher, for the exploitation of new type antineoplastic medicine provides screening of medicaments.
Specific embodiment
Embodiment 1
Compound
2aPreparation
(1.0g 0.0092mol) adds in the 30mL dry toluene, adds hexamethyldisilazane (2.2mL with uridylic; 0.010mol) and the anhydrous slufuric acid ammonium of catalytic amount, reflux to system is clarified fully, and system is cooled to 50 ℃; Be evaporated to driedly, add compound in the residuum
1(2.0g, 0.0042mol) with anhydrous methylene chloride 30mL, ice bath; The dropping anhydrous stannic chloride (1.35mL, 0.011mol), stirring at room reaction two hours; After finishing, reaction, to neutral, stirred 1 hour with saturated sodium bicarbonate solution regulation system pH with the cooling of system ice bath; Filter, filter cake is washed with ETHYLE ACETATE.Merging filtrate and washing lotion, with saturated common salt washing twice, anhydrous sodium sulfate drying, filtering and concentrating obtains compound through column chromatography then
2a
Compound
2b-2hPreparation
According to the preparation compound
2aMethod; Use 5 FU 5 fluorouracil, 5-chlorouracil, 5-bromouracil, 5-iodouracil, thymus pyrimidine, cytosine(Cyt) or 5-flurocytosine as base respectively; With Zinc Chloride Anhydrous, anhydrous boron trifluoride, trimethylammonium silication triflate or anhydrous titanium tetrachloride is catalyzer; Anhydrous acetonitrile, anhydrous 1,2-ethylene dichloride, anhydrous tetrahydro furan or anhydrous diethyl ether are organic solvent, obtain compound respectively
2b-2h
Table I compound
2a-2hStructure
Embodiment 2
Compound
3aPreparation
With compound
2a(0.58g 0.0010mol) is dissolved in the methyl alcohol saturated solution of 10ml ammonia, and stirring at room two hours is concentrated into driedly, obtains compound through column chromatography then
3a 1H?NMR?(400?MHz,?D
2O)?δ?7.63?(d,?
J?=?8.0?Hz,?1H),?7.41?(d,?
J?=?7.6?Hz,?1H),?6.31?(d,?
J?=?2.3?Hz,?1H),?5.92?(d,?
J?=?7.3?Hz,?1H),?5.82?(d,?
J?=?8.0?Hz,?1H),?5.73?(d,?
J?=?7.6?Hz,?1H),?4.69?(d,?
J?=?4.2?Hz,?1H),?4.57?(dd,?
J?=?7.3,?2.4?Hz,?1H),?4.51?(d,?
J?=?1.5?Hz,?1H),?4.40?(dd,?
J?=?3.5,?1.5?Hz,?1H),?4.32?(d,?
J?=?7.3?Hz,?1H),?2.12?–?2.00?(m,?1H),?1.90?(dd,?
J?=?6.6,?3.7?Hz,?2H),?1.61?–?1.49?(m,?1H).
?13C?NMR?(101?MHz,?CDCl
3)?δ?169.7,?168.1,?155.0,?145.6,?145.1,?106.6,?105.3,?103.4,?93.3,?90.1,?78.4,?77.5,?76.7,?74.1,?73.3,?26.4,?23.6.?HRMS:?calcd?for?C
18H
20N
4O
10Na?[M+Na]
+?475.1077,?found?475.1074.
Compound
3b-3hPreparation
According to the preparation compound
3aMethod, with compound
2b-2h, be dissolved in respectively in methyl alcohol, the ethanol, add yellow soda ash, salt of wormwood, sodium hydrogencarbonate, sodium hydroxide or Pottasium Hydroxide, deacetylate obtains compound
3b-3h
Two 5 FU 5 fluorouracil Tricyclic-nucleosides
3b,
1H NMR (400 MHz, D
2O) δ 7.85 (d,
J=6.2 Hz, 1H), 7.70 (d,
J=6.2 Hz, 1H), 5.93 (d,
J=7.1 Hz, 1H), 5.80 (d,
J=2.1 Hz, 1H), 4.62 (dd,
J=7.3,3.8 Hz, 1H), 4.54 (s, 1H), 4.40 (dd,
J=3.6,1.6 Hz, 1H), 4.30 (dd,
J=7.2,2.5 Hz, 1H), 4.06 (d,
J=7.2 Hz, 1H), 2.15 – 1.86 (m, 3H), 1.72 – 1.59 (m, 1H).
13C NMR (101 MHz, CDCl
3) δ 159.5,159.3,150.4,149.8,142.2,141.9,139.8,139.6; 126.7,126.4,126.3,125.9,104.2,92.0,90.4; 76.1,75.0,73.9,72.4,71.7,24.2,20.9. HRMS:calcd for C
18H
18F
2N
4O
10Na [M+Na]
+511.0889, found 511.0889.
Two 5-chlorouracil Tricyclic-nucleosides
3c,
1H NMR (400 MHz, D
2O) δ 7.94 (s, 1H), 7.77 (s, 1H), 5.92 (d,
J=7.3 Hz, 1H), 5.79 (d,
J=2.5 Hz, 1H), 4.63 (dd,
J=7.3,3.8 Hz, 1H), 4.54 (s, 1H), 4.41 – 4.37 (m, 1H), 4.30 (dd,
J=7.2,2.5 Hz, 1H), 4.07 (d,
J=7.3 Hz, 1H), 2.12 – 1.87 (m, 3H), 1.70 – 1.61 (m, 1H).
13C NMR (101 MHz, D
2O) δ 161.7,150.9,150.4,139.4,139.1,109.3,109.1,104.3,92.3,90.7,76.2,75.1,73.8,72.3,71.8,24.1,20.8. HRMS:calcd for C
18H
18Cl
2N
4O
10Na [M+Na]
+543.0298, found 543.09296.
Two 5-bromouracil Tricyclic-nucleosides
3d,
1H NMR (400 MHz, DMSO) δ 11.90 (s, 2H), 8.28 (s, 1H), 8.18 (s, 1H), 5.95 (d,
J=7.5 Hz, 1H), 5.75 (d,
J=3.6 Hz, 1H), 5.39 (d,
J=11.3 Hz, 1H), 5.07 (s, 1H), 4.95 (d,
J=10.4 Hz, 1H), 4.54 (d,
J=11.6 Hz, 2H), 4.17 (s, 1H), 4.10 (d,
J=1.5 Hz, 1H), 4.04 (t,
J=8.0 Hz, 1H), 1.96 – 1.74 (m, 3H), 1.58 (d,
J=9.8 Hz, 1H).
13C NMR (101 MHz, D
2O) δ 159.6,159.5,150.9,150.2,142.3,141.3,129.4,128.7,125.0,103.5,97.2,97.0,76.4,74.5,73.8,71.8,71.7,56.5,24.8,21.9. HRMS:calcd for C
18H
18Br
2N
4O
10Na [M+Na]
+632.9267, found 632.9266.
Two 5-iodouracil Tricyclic-nucleosides
3e,
1H NMR (400 MHz, DMSO) δ 11.77 (s, 2H), 8.23 (s, 1H), 8.15 (s, 1H), 5.92 (d,
J=7.6 Hz, 1H), 5.72 (d,
J=3.6 Hz, 1H), 5.37 (d,
J=11.6 Hz, 1H), 5.05 (d,
J=5.4 Hz, 1H), 4.93 (d,
J=10.8 Hz, 1H), 4.60 – 4.49 (m, 2H), 4.17 (s, 1H), 4.10 (s, 1H), 4.07 – 3.99 (m, 1H), 1.96 – 1.73 (m, 3H), 1.54 (t,
J=11.4 Hz, 1H).
13(101 MHz, DMSO) δ 161.0,160.9,151.2,150.6,147.0,145.9,103.5,92.0,89.2,76.4,74.5,73.7,71.7,71.0,70.8,24.8,21.9. HRMS:calcd for C for C NMR
18H
18I
2N
4O
10Na [M+Na]
+726.9010, found 726.9014.
Two thymus pyrimidine Tricyclic-nucleosides
3f,
1H NMR (400 MHz, D
2O) δ 7.41 (s, 1H), 7.25 (s, 1H), 5.87 (d,
J=7.4 Hz, 1H), 5.75 (d,
J=2.6 Hz, 1H), 4.63 (dd,
J=7.4,3.7 Hz, 1H), 4.49 (s, 1H), 4.38 – 4.32 (m, 1H), 4.29 (dd,
J=7.3,2.6 Hz, 1H), 4.06 (d,
J=7.3 Hz, 1H), 2.06 – 1.83 (m, 3H), 1.76 (s, 3H), 1.74 (s, 3H), 1.59 (d,
J=12.2 Hz, 1H).
13C NMR (101 MHz, CDCl
3) δ 166.3,151.7,151.3,138.4,138.0,111.8,111.5,104.0,92.0,90.1,75.6,74.8,74.8,73.9,72.0,71.6,30.1,24.0,20.0,11.4,11.3. HRMS:calcd for C
20H
24N
4O
10Na [M+Na]
+503.1390, found 503.1394.
Two cytosine(Cyt) Tricyclic-nucleosides
3g,
1H NMR (400 MHz, D
2O) δ 7.48 (d,
J=7.8 Hz, 1H), 7.32 (d,
J=6.8 Hz, 1H), 6.22 (d,
J=2.2 Hz, 1H), 5.87 (d,
J=7.0 Hz, 1H), 5.78 (d,
J=7.8 Hz, 1H), 5.74 (d,
J=6.8 Hz, 1H), 4.69 (d,
J=4.2 Hz, 1H), 4.57 (dd,
J=7.3,2.4 Hz, 1H), 4.51 (d,
J=1.5 Hz, 1H), 4.40 (dd,
J=3.5,1.5 Hz, 1H), 4.32 (d,
J=7.3 Hz, 1H), 2.12 – 1.83 (m, 3H), 1.52 – 1.33 (m, 1H).
13C NMR (101 MHz, CDCl
3) δ 169.6,168.0,153.0,150.6,143.1,104.6,102.3,101.4,90.3,88.1,76.4,75.5,74.7,73.9,73.3,26.5,23.2. HRMS:calcd for C
18H
20F
2N
6O
8Na [M+Na]
+473.1397, found 473.1396.
Two 5-flurocytosine Tricyclic-nucleosides
3h,
1H NMR (400 MHz, D
2O) δ 7.77 (dd,
J=6.1,1.0 Hz, 1H), 7.61 (dd,
J=6.1,2.5 Hz, 1H), 5.91 (d,
J=7.3 Hz, 1H), 5.77 (s, 1H), 4.63 (dd,
J=6.5,3.3 Hz, 1H), 4.52 (s, 1H), 4.45 – 4.34 (m, 1H), 4.24 (d,
J=7.1 Hz, 1H), 4.04 (d,
J=6.3 Hz, 1H), 2.15 – 1.87 (m, 3H), 1.70 – 1.61 (m, 1H).
13C NMR (101 MHz, CDCl
3) δ 158.5,158.4,158.4,158.3,156.1,155.4; 138.9,138.7,136.5,136.2,126.7,126.5; 126.3,126.2,104.3,92.8,91.2,76.3; 74.8,74.0,72.8,71.9,24.2,20.9. HRMS:calcd for C
18H
20F
2N
6O
8Na [M+Na]
+509.1208, found 509.1207.
Table II compound
3a-3hStructure
Embodiment 3
Sulfadiazine Compound base tricyclic-nucleoside prodrugs
3a-3hTo Ec9706, Ec109, MGC-803, PC-3 and S180 five strain tumor cell proliferation inhibition effects
Five strain tumour cells with the positive contrast of 5 FU 5 fluorouracil, adopt four tetrazolium bromides (MTT) method to compound through cultivating the back respectively at inoculating in 96 orifice plates
3a-3hUnder 128 μ g/mL concentration, screen for the first time, medicine and cytosis 72 h, inhibiting rate is greater than 50%, and being considered to has restraining effect to the propagation of this tumour cell, further measure IC then
50Value.The result finds compound
3ePropagation to human esophagus cancer Ec109 cell has restraining effect, all the other compounds to five kinds of tumor cell proliferation inhibition rates all less than 50%.Again with compound
3eAccording to certain concentration gradient 8 different concentration are set, parallel 6 times of each concentration, exercising result adopts the SPSS16.0 statistical software to carry out regression analysis and handles, and draws compound
3eIC
50Value is 31.312 μ g/mL.
Embodiment 4
Compound
3b, 3cWith
3hAnti-tumor in vivo in transplantability mouse S180 sarcoma model is active
Collect the S180 ascitic tumor fluid of cultivating 8 days, cell concn is adjusted into 5 * 10 with saline water
7Individual cells/ml carries out aseptic subcutaneous vaccination, every mouse inoculation 0.2 mL cell suspension in mouse (SPF rank Kunming mouse, body weight are 18 ~ 22 g, male and female half and half, Henan Province's Experimental Animal Center provides) right fore.Establish 10 groups altogether, 10 every group, respectively establish 50 mg/kg, 100mg/kg, 200 mg/kg, three dose groups, positive controls give 5 FU 5 fluorouracil 15 mg/kg, and negative control group gives aseptic 0.9% saline water (NS) 10mL/Kg.Begin the tail intravenously administrable next day from mouse inoculation, the tail intravenously administrable is 10 days continuously, weighs, surveys the knurl body every other day, observes state and the death condition of every animal.Disconnected neck is put to death animal after 11 days, peels off the knurl body, claims that knurl is heavy, and calculates tumour inhibiting rate by following formula: tumour inhibiting rate=(the average knurl of the average knurl weight-administration of control group group is heavy)/average knurl of control group heavy * 100%.Experimental result with mean ± standard deviation (
x±
s) expression, adopt SPSS16.0 software that the result is analyzed, utilize one-way analysis of variance to compare.The result is the significance standard by P=0.05.
Table III compound
3b, 3cWith
3hRestraining effect to mouse S180 solid tumor
*P＜0.05，**P＜0.01
Experimental result (table 1) shows, compound
3bWith
3hGrowth to mouse interior tumor has obvious suppression effect, compound
3cA little less than the growth-inhibiting effect very to mouse interior tumor.The compound of various dose
3bWith
3hAnd all remarkable (P of the tumour inhibiting rate difference between the negative control group<0.05).Compound wherein
3bWith
3hWhen low dosage (50 mg/kg), tumour is shown good restraining effect (63.13% and 51.38%), effect is superior to 5 FU 5 fluorouracil (51.04%), compound
3bAnti-tumor activity be superior to compound
3h
It is used for preparing antitumor drug as activeconstituents, can processes oral type preparation or injection-type preparation medicine.
The oral type preparation is tablet, pill, capsule, electuary or syrup; The injection-type preparation is injection liquid or freeze-dried powder formulation.
Claims (9)
1. one type of Sulfadiazine Compound base tricyclic-nucleoside prodrugs is characterized in that having following general structure:
R wherein
1During for OH, R
2Be selected from H, F, Cl, Br, I or CH
3R
1Be NH
2The time, R
2Be selected from H, F.
2. one type of Sulfadiazine Compound base tricyclic-nucleoside prodrugs is characterized in that having following general structure:
R wherein
1During for OH, R
2Be selected from H, F, Cl, Br, I or CH
3R
1Be NH
2The time, R
2Be selected from H, F.
3. a method for preparing the described Sulfadiazine Compound base of claim 1 tricyclic-nucleoside prodrugs is characterized in that, in the organic solvent, with compound
1React under the effect of catalyzer with the pyrimidine of trimethyl silicon based protection, obtain compound
2a-2hCatalyzer is selected from Zinc Chloride Anhydrous, anhydrous boron trifluoride, anhydrous stannic chloride, trimethylammonium silication triflate or anhydrous titanium tetrachloride; Said organic solvent is selected from anhydrous acetonitrile, anhydrous 1,2-ethylene dichloride, anhydrous methylene chloride, anhydrous tetrahydro furan or anhydrous diethyl ether;
4. a method for preparing the described Sulfadiazine Compound base of claim 2 tricyclic-nucleoside prodrugs is characterized in that, in the solvent, with compound
2a-2hDeacetylate obtains compound under the effect of alkali
3a-3hSaid solvent is selected from methyl alcohol, ethanol or water; Alkali is selected from yellow soda ash, salt of wormwood, sodium hydrogencarbonate, sodium hydroxide, Pottasium Hydroxide or ammonia.
5. the method for preparing the described Sulfadiazine Compound base of claim 1 tricyclic-nucleoside prodrugs according to claim 3; It is characterized in that said pyrimidine is selected from uridylic, 5 FU 5 fluorouracil, 5-chlorouracil, 5-bromouracil, 5-iodouracil, thymus pyrimidine, 5-flurocytosine or cytosine(Cyt).
6.
The application of the described Sulfadiazine Compound base of claim 1 tricyclic-nucleoside prodrugs in the preparation medicine is characterized in that, it is used for preparing antitumor drug as activeconstituents.
7. the application of the described Sulfadiazine Compound base of claim 2 tricyclic-nucleoside prodrugs in the preparation medicine is characterized in that, it is used for preparing antitumor drug as activeconstituents.
8. like claim 6 or the application of 7 described Sulfadiazine Compound base tricyclic-nucleoside prodrugs in the preparation medicine, it is characterized in that, it is prepared into oral type preparation or injection-type preparation medicine.
9. the application of Sulfadiazine Compound base tricyclic-nucleoside prodrugs as claimed in claim 8 in the preparation medicine is characterized in that the oral type preparation is tablet, pill, capsule, electuary or syrup; The injection-type preparation is injection liquid or freeze-dried powder formulation.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210333899XA CN102827223A (en) | 2012-09-11 | 2012-09-11 | Di-pyrimidine base tricyclic nucleoside compound, and synthetics method and pharmaceutical use thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210333899XA CN102827223A (en) | 2012-09-11 | 2012-09-11 | Di-pyrimidine base tricyclic nucleoside compound, and synthetics method and pharmaceutical use thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN102827223A true CN102827223A (en) | 2012-12-19 |
Family
ID=47330557
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201210333899XA Pending CN102827223A (en) | 2012-09-11 | 2012-09-11 | Di-pyrimidine base tricyclic nucleoside compound, and synthetics method and pharmaceutical use thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102827223A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103232509A (en) * | 2013-05-14 | 2013-08-07 | 郑州大学 | Fluorouracil compound, and preparation method and application thereof |
| CN105001290A (en) * | 2015-07-15 | 2015-10-28 | 郑州大学 | Dipyrimidine bases tricyclic nucleoside compound and preparation method therefor and application thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1523030A (en) * | 2003-09-05 | 2004-08-25 | 郑州大学 | C10 high carbon sugar derivative, preparation method and use thereof |
-
2012
- 2012-09-11 CN CN201210333899XA patent/CN102827223A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1523030A (en) * | 2003-09-05 | 2004-08-25 | 郑州大学 | C10 high carbon sugar derivative, preparation method and use thereof |
Non-Patent Citations (1)
| Title |
|---|
| 许卫超: "新型C10高碳糖核苷类化合物及其胺基衍生物的合成研究", 《中国优秀博硕士学位论文全文数据库（硕士）医药卫生科技辑》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103232509A (en) * | 2013-05-14 | 2013-08-07 | 郑州大学 | Fluorouracil compound, and preparation method and application thereof |
| CN103232509B (en) * | 2013-05-14 | 2015-07-08 | 郑州大学 | Fluorouracil compound, and preparation method and application thereof |
| CN105001290A (en) * | 2015-07-15 | 2015-10-28 | 郑州大学 | Dipyrimidine bases tricyclic nucleoside compound and preparation method therefor and application thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP6769000B2 (en) | A novel compound of 4'-thionucleoside, its preparation method, its pharmaceutical composition and its use | |
| CN103044395B (en) | Desloratadine-containing amino acid derivative as well as preparation method and application thereof | |
| CN107163026A (en) | Salt of pyridine amine pyrimidine derivates and its preparation method and application | |
| CN102924507A (en) | An anti-tumor compound and its preparation method, application, and pharmaceutical compositions | |
| CN101735276A (en) | Water-soluble phosphate monoester derivatives and application thereof | |
| CN102827223A (en) | Di-pyrimidine base tricyclic nucleoside compound, and synthetics method and pharmaceutical use thereof | |
| CN101062041B (en) | Novel medical function of cucurbitacin | |
| CN101519423B (en) | Betulinic acid analogue and preparation method and application thereof | |
| CN101129387A (en) | New medical use of cucurbitacin in treating cancer | |
| CN101863901B (en) | 2-(substituted phenyl)-2-(4,5,6,7-thiophane[3,2-c] pyridine-5(4H)-group)-N-substitute-acetamide as well as preparation method and application thereof | |
| CN102911118A (en) | Benzo-azepine type derivative and preparation method and purpose thereof | |
| CN101107261B (en) | Imidazopyridine derivative | |
| CN103864765A (en) | Benzoazepine derivative containing five-membered heterocycle as well as preparation method and application of derivative | |
| CN102746212B (en) | Beta-elemene indole derivative, preparation and application thereof | |
| CN112409431B (en) | Cytarabine structural analogue, and preparation method and application thereof | |
| CN101541717B (en) | A trans-cinnamic acid derivative, its preparation method and the use | |
| CN101602786A (en) | N 6-substituted adenosines derivative, its method for making and pharmaceutical composition and purposes | |
| CN102786458B (en) | Pyrrole formamide derivative, and preparation method and application thereof | |
| CN109846873B (en) | Anti-tumor medicine composition | |
| CN110746392B (en) | Application of furan compounds in preparation of antitumor drugs | |
| CN105001290A (en) | Dipyrimidine bases tricyclic nucleoside compound and preparation method therefor and application thereof | |
| CN104926804A (en) | Compounds with anti-tumor effect, and preparation method and application of compounds | |
| CN102115485A (en) | Prodrug based on cytosine arabinoside structure, and synthesis method and application thereof | |
| CN101684123B (en) | Preparation method of 2-formamido thienopyridine derivatives and medical uses | |
| CN109956907A (en) | A kind of ubenimex prodrug derivant and its preparation and use |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C12 | Rejection of a patent application after its publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20121219 |