2apos; -deoxy-2apos;-(2apos); -fluoro-4apos,-fluoro-4apos; preparation and pharmaceutical application of-azido-vidarabine N6-acyl substituted compound
By designing and preparing 2'-deoxy-2'-fluoro-4'-azido-ada adenosine N6-acyl substituted compounds, the selection and stability of existing anti-tumor drugs are solved, and efficient anti-tumor is achieved Activity and stability, especially in anti-hepatic cancer, show significant tumor-inhibiting effects, are suitable for large-scale production and reduce costs.
Patent Information
- Application Number
- CN202411305938.4
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-09-19
- Publication Date
- 2025-01-03
AI Technical Summary
Existing anti-tumor drugs are not selective and prone to inactivation in the body, resulting in poor efficacy. It is necessary to develop a compound that is not prone to inactivation in the body and has anti-tumor activity.
Design and prepare 2'-deoxy-2'-fluoro-4'-azido-ada adenosine N6-acyl substituted compounds, through a series of condensation, deBz, iodine, double bonds, azide, deiodine and amide synthesis routes to obtain compounds with potential antitumor activity.
The high activity and stability of the compound are achieved, and can be effectively used for the preparation of anti-tumor drugs, especially in anti-hepatic cancer, which shows significant tumor-inhibiting effects, and is suitable for large-scale production, reducing costs.
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Figure CN119241621A_ABST
Abstract
Description
Technical Field
[0001] The present invention belongs to the technical field of pharmaceutical chemistry, and specifically relates to a class of 2'-deoxy-2'-fluoro-4'-azido-adenosine N 6 -A preparation method of acyl substituted compounds and their anti-tumor activity application. Background Art
[0002] Over the past century, drug treatment of cancer has achieved remarkable results, and dozens of anti-tumor drugs have been developed, which effectively prolong the life of patients or improve their quality of life. However, most drugs are cytotoxic drugs, which are not highly selective and have drug resistance problems. Therefore, the research and development of anti-tumor drugs still face huge challenges, and the research of anti-tumor drugs is still one of the important tasks in the medical field. In order to improve the efficacy of tumor treatment and achieve new breakthroughs, designing more effective drugs is an urgent issue.
[0003] Adenosine is a good antiviral drug in the pharmaceutical field and is also the starting material for the combined development of new anti-hepatitis B, anti-AIDS, anti-tumor and other therapeutic drugs. Recently, more and more studies have shown that 8-chlorocyclic adenosine monophosphate and its metabolite 8-chloroadenosine have good anti-tumor activity and have entered the clinical trial stage. However, since they are easily hydrolyzed by deaminase in the body to generate inosine analogs and become inactivated, it is very necessary to perform certain structural modifications on this type of compound.
[0004] 2'-Deoxy-2'-fluoro-4'-azido-adenosine N 6 -Acyl substituted compounds are a class of lead compounds with potential anti-tumor activity, and no relevant literature has been reported so far. Summary of the invention
[0005] The present invention aims to overcome the defects of the prior art and provide a class of 2'-deoxy-2'-fluoro-4'-azido-arabinoadenosine N- 6 -Acyl-substituted compounds and their antitumor activity can be achieved at low cost and suitable for large-scale production needs.
[0006] The present invention also provides the above-mentioned 2'-deoxy-2'-fluoro-4'-azido-adenosine N 6 -Application of acyl substituted compounds in the preparation of anti-tumor active drugs.
[0007] To achieve the above object, the present invention adopts the following technical solution:
[0008] A class of 2'-deoxy-2'-fluoro-4'-azido-adenosine N 6 -Acyl substituted compounds having the following structural formula I:
[0009] Where R is C1-C 10 Straight or branched chain alkanes.
[0010] The 2'-deoxy-2'-fluoro-4'-azido-adenosine N 6 - an acyl substituted compound, which is preferably one of the following compounds:
[0011]
[0012] The present invention provides the above-mentioned 2'-deoxy-2'-fluoro-4'-azido-adenosine N 6 -acyl substituted compounds in the preparation of anti-tumor drugs. Further preferably, 2'-deoxy-2'-fluoro-4'-azido-arabinovir disoproxil N 6 -Application of acyl substituted compounds in the preparation of anti-liver cancer drugs.
[0013] The 2'-deoxy-2'-fluoro-4'-azido-adenosine N 6 -Acyl substituted compounds, the synthesis route of which is as follows:
[0014]
[0015] a. Condensation reaction
[0016] Compound 1 was dissolved in acetonitrile, benzoyl adenine and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) were added, and trifluoromethanesulfonic anhydride trimethylsilyl ether (TMSOTf) was slowly added dropwise. The mixture was heated to 80 degrees and stirred for 6 hours. The reaction of the raw materials was completed after TLC monitoring. After cooling to room temperature, the mixture was slowly poured into a saturated sodium bicarbonate solution, extracted with dichloromethane, dried, and distilled under reduced pressure to obtain compound 2.
[0017] b. De-Bz reaction:
[0018] Dissolve compound 2 in a half-saturated ammonia methanol (NH3 / CH3OH) solution and stir at room temperature overnight. After the reaction of the raw material is complete, monitor by TLC. After the ammonia methanol solution is evaporated under reduced pressure, add dichloromethane and stir vigorously to precipitate a solid, which is then filtered and dried to obtain compound 3.
[0019] c. Iodination reaction:
[0020] Dissolve compound 3 in tetrahydrofuran, add triphenylphosphine and imidazole, cool to 0°C, slowly add iodine solution in tetrahydrofuran, stir and react at room temperature for 12 hours, monitor the reaction of the raw materials by TLC, slowly add saturated sodium sulfite solution, extract with ethyl acetate, dry, filter and concentrate to obtain a viscous substance, add a small amount of methanol and stir overnight, filter and dry to obtain compound 4.
[0021] d. Double bond reaction:
[0022] Compound 4 was added with methanol, and then sodium methoxide was slowly added, refluxed for 6 hours, cooled to room temperature, neutralized to neutrality by adding dilute hydrochloric acid, and then saturated sodium bicarbonate solution was added, extracted with ethyl acetate, the organic phases were combined, dried, filtered, and concentrated to dryness under reduced pressure to obtain compound 5, which was directly used in the next step reaction.
[0023] e. Azide reaction:
[0024] Sodium azide was added to tetrahydrofuran, and iodine chloride was slowly added under ice bath conditions for 0.5 h. Then, a tetrahydrofuran solution of compound 5 was slowly added. After half an hour, the temperature was warmed to room temperature and stirred for 12 h. After complete reaction, a saturated sodium bisulfite solution was added. The mixture was extracted with ethyl acetate, dried, filtered, concentrated to dryness under reduced pressure, and subjected to column chromatography to obtain compound 6.
[0025] f. Deiodination reaction:
[0026] Compound 6 was dissolved in ethanol, sodium hydroxide solution was added and stirred at room temperature for 16 hours. After the reaction was complete, it was neutralized with dilute hydrochloric acid until neutral. After concentration to dryness, compound 7 was obtained by column chromatography.
[0027] g. Synthesis of amide:
[0028] Compound 7 was dissolved in ethanol, and then various acid anhydrides were added. The temperature was raised to 80 degrees and stirred for 6-18 hours. The reaction was completed after monitoring by TLC. The solvent was evaporated under reduced pressure and compound I was obtained by column chromatography.
[0029] Compared with the prior art, the present invention has the following technical effects:
[0030] The compounds of the present invention can be used as active ingredients of antiviral drugs, and can be used alone or in combination with other antiviral drugs. The combined drug treatment process referred to in the present invention includes the use of at least one compound of the present invention or its active derivatives together with one or more other antiviral drugs to increase the overall therapeutic effect. The dosage and administration time of combined drug use should be determined according to the most reasonable therapeutic effect achieved in different situations. The compounds in the general formula of the present invention are used to prepare drugs for treating, preventing or alleviating diseases caused by a certain virus. The viruses referred to include but are not limited to cancer viruses. BRIEF DESCRIPTION OF THE DRAWINGS
[0031] Figure 1 These are the tumor pictures of 2 mice in the blank group:
[0032] Figure 2 These are the tumor images of 4 mice in the TL001 administration group:
[0033] Figure 3 These are pictures of tumors in 4 mice in the TL002-administered group. DETAILED DESCRIPTION
[0034] The technical solution of the present invention is further described in detail below in conjunction with the embodiments, but the protection scope of the present invention is not limited thereto.
[0035] In the following examples, unless otherwise specified, the raw materials used are common commercial products that can be directly purchased or can be prepared using conventional techniques in the art.
[0036] Room temperature refers to 25±5°C.
[0037] Example 1: Synthesis of Compound 2:
[0038] Compound 1 fluorosugar (2-deoxy-2-fluoro-1,3,5-tribenzoyl-α-D-arabinofuranosyl, 92.8 g, 0.2 mol) was dissolved in acetonitrile (500 ml) and N 6 -benzoyl adenine (71.8 g, 0.3 mol), DBU (136.8 g, 0.9 mol), slowly add TMSOTf (200.0 g, 0.9 mol), heat to 80 degrees and stir to react for 6 hours, TLC monitors the reaction of the raw materials, cool to room temperature and slowly pour into saturated sodium bicarbonate solution, extract with dichloromethane, dry, distill under reduced pressure, column chromatography (ethyl acetate: petroleum ether = 1:1, V / V), concentrate to dryness, and obtain a light white solid compound 2 (91.8 g, 79%). Compound 2 1 The H spectrum data are shown below.
[0039] 1 H NMR(400MHz, CDCl3)δ:8.67(s,1H),8.55(s,1H),8.13(brs,1H),8.08-7.38(m,15H),5.97(d,1H,J =7.6, Hz), 5.82 (d, 1H, J = 5.2Hz), 5.01 (d, 1H, J = 5.2Hz), 4.88 (dd, 1H, J = 48.8, 5.2Hz), 4.32 (m, 2H).
[0040] Example 2: Synthesis of Compound 3:
[0041] Compound 2 (87.2 g, 0.15 mol) was dissolved in a half-saturated ammonia methanol solution (600 ml), stirred at room temperature for 12 h, and after TLC monitoring, the ammonia methanol solution was evaporated under reduced pressure, and dichloromethane was added and stirred vigorously to precipitate solids, which were filtered, washed with a small amount of dichloromethane, and dried in vacuo to obtain white solid compound 3 (38.7 g, 96%). 1 H. 13 C spectrum data are shown below.
[0042] 1 H NMR (400 MHz, DMSO-d6) δ: 8.72 (s, 1H), 8.68 (s, 1H), 7.30 (brs, 2H, disappeared by D2O exchange), 6.05 (d, 1H, J=7.6, Hz), 5.53 (brs, 1H, disappeared by D2O exchange), 5.22 (brs, 1H, disappeared by D2O exchange), 5.14 (d, 1H, J=5.2 Hz), 4.62 (d, 1H, J=5.2 Hz,), 3.98 (dd, 1H, J=45.8, 4.8 Hz), 3.68 (m, 1H), 3.56 (m, 1H).
[0043] 13 C NMR(101MHz,DMSO-d6)δ:162.4,151.8,149.9,142.8,124.2,87.7(d,J FC =190Hz),85.8,73.7(m),70.4(t,J FC =24Hz),61.4.
[0044] Example 3: Synthesis of Compound 4:
[0045] Compound 3 (32.3 g, 0.12 mol) was dissolved in tetrahydrofuran (300 mL), triphenylphosphine (48.1 g, 0.18 mol) and imidazole (16.3 g, 0.24 mol) were added, and the mixture was cooled to zero degrees. A tetrahydrofuran solution of iodine (44.9 g, 0.18 mol) was slowly added. The mixture was stirred at room temperature for 12 hours. After the reaction of the raw materials was complete as monitored by TLC, a saturated sodium sulfite solution was slowly added. The mixture was extracted with ethyl acetate (3×300 mL), dried over anhydrous sodium sulfate, filtered, and concentrated to obtain a viscous substance. Methanol was added and stirred overnight (12 h). A slightly yellow solid was precipitated. The mixture was filtered and dried to obtain compound 4 (40.1 g, 88%). 1 H. 13 C spectrum data are shown below.
[0046] 1 H NMR (400 MHz, DMSO-d6) δ: 8.76 (s, 1H), 8.70 (s, 1H), 7.33 (brs, 2H, disappeared by D2O exchange), 6.26 (d, 1H, J = 7.6, Hz), 5.34 (brs, 1H, disappeared by D2O exchange), 5.16 (d, 1H, J = 5.3 Hz), 4.64 (d, 1H, J = 5.3 Hz,), 4.12 (dd, 1H, J = 46.8, 5.6 Hz), 3.62 (m, 2H).
[0047] 13 C NMR(101MHz,DMSO-d6)δ:163.8,152.6,151.2,144.3,125.6,91.6(d,J FC =192Hz),88.1,76.5,72.6(J FC =28Hz),63.4.
[0048] Example 4: Synthesis of Compound 5:
[0049] Compound 4 (37.9 g, 0.1 mol) was added with methanol (300 mL), and then sodium methoxide (21.6 g, 0.4 mol). After reflux reaction for 8 hours, it was cooled to room temperature, and dilute hydrochloric acid (2 mol / L) was slowly added to neutralize to pH = 7-8. Saturated sodium bicarbonate solution (300 ml) was added, and ethyl acetate was extracted (6×500 mL). The organic phases were combined, dried over anhydrous sodium sulfate, filtered, concentrated to dryness under reduced pressure, and passed through a flash column (dichloromethane: methanol = 10:1, V / V) to obtain a white solid compound 5 (20.6 g, 82%), which was directly used in the next step. Compound 5 1 H. 13 C spectrum data are shown below.
[0050] 1 H NMR (400 MHz, CDCl3) δ: 8.68 (s, 1H), 8.57 (s, 1H), 7.26 (brs, 2H, disappeared by D2O exchange), 6.58 (dd, 1H, J = 21.2, 2.4 Hz), 5.78 (d, 1H, J = 7.8 Hz), 5.14 (dd, 1H, J = 48.6, 2.4 Hz), 4.78 (d, 1H, J = 2.4 Hz), 4.78 (d, 1H, J = 11.8 Hz), 4.52 (d, 1H, J = 2.4 Hz).
[0051] 13 C NMR(101MHz,DMSO-d6)δ:164.6,153.7 152.4,145.6,126.1,98.7(d,J FC =198Hz),92.4,81.6,76.8(J FC =24Hz),64.2.
[0052] Example 5: Synthesis of Compound 6:
[0053] Sodium azide (23.1 g, 0.35 mol) was added to tetrahydrofuran (100 ml), and iodine chloride (28.7 g, 0.18 mol) was slowly added under ice bath conditions, and the reaction was continued for 0.5 hours. Compound 5 (20.1 g, 0.08 mol) was dissolved in tetrahydrofuran (200 mL), and then carefully poured into the above reaction solution. After half an hour, the mixture was heated to room temperature and stirred for 12 hours. After the reaction was complete, a saturated sodium bisulfite solution was slowly added to the above reaction solution. After the color of the solution faded, it was extracted with ethyl acetate (3×300 mL), the organic phases were combined, dried over anhydrous sodium sulfate, filtered, concentrated to dryness under reduced pressure, and concentrated to dryness by column chromatography (dichloromethane: methanol = 20:1, V / V) to obtain a slightly yellow solid compound 6 (28.6 g, 85%). 1 H. 13 C spectrum data are shown below.
[0054] 1 H NMR (400 MHz, DMSO-d6) δ: 8.78 (s, 1H), 8.72 (s, 1H), 7.39 (brs, 2H, disappeared by D2O exchange), 6.34 (d, 1H, J = 7.2 Hz), 5.51 (brs, 1H, disappeared by D2O exchange), 5.24 (d, 1H, J = 5.4 Hz), 4.12 (dd, 1H, J = 48.6, 5.4 Hz), 3.58 (m, 2H).
[0055] 13 C NMR(101MHz,DMSO-d6)δ:164.3,153.2,152.3,145.1,126.5,92.3(d,J FC =187Hz),89.2,77.2 73.4(J FC =26Hz),65.1.
[0056] Example 6: Synthesis of Compound 7:
[0057] Compound 6 (25.2 g, 0.06 mol) was dissolved in ethanol (60 mol), and sodium hydroxide solution (60 ml, 20%, W / W) was added and stirred at room temperature for 16 h. After the reaction was complete, it was neutralized with dilute hydrochloric acid (2 mol / L) until neutral, concentrated to dryness, and column chromatography (dichloromethane: methanol = 10:1, V / V) was performed, and concentrated to dryness to obtain a powdery white solid compound 7 (18.2 g, 98%). 1 H. 13 C spectrum data are shown below.
[0058] 1HNMR (400 MHz, DMSO-d6) δ: 8.72 (s, 1H), 8.66 (s, 1H), 7.41 (brs, 2H, disappeared by D2O exchange), 6.26 (dd, 1H, J = 11.2 Hz, 5.6 Hz,), 5.62 (brs, 1H, disappeared by D2O exchange), 5.34 (brs, 1H, disappeared by D2O exchange), 5.22 (dt, 1H, J = 52 Hz, 5.2 Hz), 4.41 (dd, 1H, J = 21.6 Hz, 4.6 Hz), 3.68 (m, 2H).
[0059] 13 C NMR(101MHz,DMSO-d6)δ:163.1,151.5,150.8,143.2,125.1,90.6(d,J FC =189Hz),87.2,76.4,72.1(J FC =24Hz),62.3.
[0060] Example 7: Synthesis of compound TL001:
[0061] Compound 7 (0.31 g, 1 mmol) was dissolved in ethanol (2 ml), and then propionic anhydride (2 ml) was added. The temperature was raised to 80 degrees and stirred for 6 hours. The reaction was monitored by TLC. The solvent was evaporated under reduced pressure, and the mixture was subjected to column chromatography (dichloromethane: methanol = 10:1, V / V). The mixture was concentrated to dryness to obtain a dark yellow crystalline compound TL001 (0.35 g, 96%). 1 H. 13 C spectrum data are shown below.
[0062] 1 HNMR (400 MHz, DMSO-d6) δ: 8.69 (s, 1H), 8.63 (s, 1H), 8.58 (brs, 1H), 6.38 (dd, 1H, J = 9.2 Hz, 5.2 Hz,), 5.66 (brs, 1H, disappeared by D2O exchange), 5.23 (dt, 1H, J = 53.6 Hz, 5.2 Hz), 4.53 (brs, 1H, disappeared by D2O exchange), 4.38 (dd, 1H, J = 21.6 Hz, 4.6 Hz), 3.72 (m, 2H), 2.11 (m, 2H), 1.05 (m, 3H).
[0063] 13 C NMR(101MHz,DMSO-d6)δ:175.4,162.9,151.3,150.5,142.8,124.7,89.6(d,J FC =190Hz),86.9,76.1,71.8(JFC =26Hz),62.5,35.8,19.2.
[0064] Example 8: Synthesis of compound TL002:
[0065] Compound 7 (0.31 g, 1 mmol) was dissolved in ethanol (2 ml), and then isobutyric anhydride (2 ml) was added, and the temperature was raised to 80 degrees and stirred for 8 hours. The reaction was completed by TLC monitoring, and the solvent was evaporated under reduced pressure. Column chromatography (dichloromethane: methanol = 10:1, V / V) was performed and concentrated to dryness to obtain a powdery gray-white compound TL002 (0.36 g, 96%). 1 H. 13 C spectrum data are shown below.
[0066] 1 HNMR (400 MHz, DMSO-d6) δ: 10.67 (brs, H), 8.78 (s, 1H), 8.69 (s, 1H), 6.26 (dd, 1H, J = 9.2 Hz, 5.4 Hz,), 5.68 (brs, 1H, disappeared by D2O exchange), 5.39 (brs, 1H, disappeared by D2O exchange), 5.22 (dt, 1H, J = 48.6 Hz, 5.2 Hz), 4.28 (dd, 1H, J = 21.6 Hz, 4.8 Hz), 3.70 (m, 2H), 2.89 (m, 1H), 1.13 (m, 1H), 1.05 (m, 1H).
[0067] 13 C NMR(101MHz,DMSO-d6)δ:177.9,163.3,151.8,151.2,143.6,125.3,90.2(d,J FC =190Hz),86.4,76.8,72.5(J FC =22Hz),62.3,36.2,19.3,18.9.
[0068] The above descriptions are only some embodiments of the present invention and do not limit the present invention in any form. Any simple modifications, equivalent changes and modifications made to the above embodiments based on the technical essence of the present invention are within the scope of the technical solution of the present invention.
[0069] The compounds synthesized in the present invention can be used as active ingredients of antiviral drugs, and can be used alone or in combination with other antiviral drugs. The combined drug treatment process referred to in the present invention includes the use of at least one compound of the present invention or its active derivatives together with one or more other antiviral drugs to increase the overall therapeutic effect. The dosage and administration time of combined drug use should be determined according to the most reasonable therapeutic effect achieved in different situations.
[0070] The compounds in the general formula of the present invention are used for the preparation of drugs for treating, preventing or alleviating diseases caused by certain viruses, including but not limited to cancer viruses.
[0071] Application example: Anti-cancer viral activity
[0072] The compounds encompassed by the present invention possess antiviral activity, including anti-cancer viral activity.
[0073] Toxicity screening test for TL001 and TL002 compounds
[0074] 1. Sample
[0075] Sample: TL001 is a crystalline dark yellow compound, and sample TL002 is a powdery grayish white compound. When testing, the sample is mixed with physiological saline to prepare a solution with a concentration of 0.015 g / mL for later use.
[0076] 2. Experimental Animals
[0077] 16 SPF KM mice, half male and half female, weighing 25-45 g, provided by Southern Medical University, Laboratory Animal Production License No.: SCXK (Guangdong) 2016-0041.
[0078] 3. Rearing conditions
[0079] The animals were kept in barrier environment IVC cages, 4 per cage. The temperature of the facility was 20-26℃, and the humidity was 40-70%. The feed supplier was Synergy Biological, and the production license number was Su Feed Certificate (2014) 01008.
[0080] 4. Test methods
[0081] The sample solution of 60mg / kg, 120mg / kg, 360mg / kg and 480mg / kg was administered orally to two animals of each dose, half of which were male and half were female. After exposure, the poisoning symptoms, death number and death time of the animals were observed for 14 days.
[0082] 5. Test results
[0083] See Table 1 and Table 2 for medication and observation record.
[0084] 6. Result Evaluation
[0085] Oral LD 50 / (mg / kg)>480.
[0086]
[0087] Note: “-” indicates that the symptom did not occur, and “N” indicates that no obvious abnormality was found.
[0088]
[0089] Note: “-” indicates that the symptom did not occur, and “N” indicates that no obvious abnormality was found.
[0090] Study on the anti-tumor effect of TL001 and TL002 compounds
[0091] 7. Samples
[0092] Sample TL001 is a crystalline dark yellow compound, and sample TL002 is a powdery grayish white compound. During testing, the samples were mixed with physiological saline to prepare a solution with a concentration of 0.015 g / mL for later use.
[0093] 8. Experimental Animals
[0094] 10 SPF Balb / c nude mice, with HepG2 human liver cancer cell tumors implanted subcutaneously on the right back, weighing 18-20g. Provided by Weitong Lihua, experimental animal use license number: SYXK (Guangdong) 2019-0201.
[0095] IX. Rearing conditions
[0096] The animals were kept in barrier environment IVC cages, 2 per cage. The temperature of the facility was 20-26℃, and the humidity was 40-70%. The feed supplier was Synergy Biological, and the production license number was Su Feed Certificate (2014) 01008.
[0097] 10. Test methods
[0098] There were 2 animals in the blank group, and 4 animals in each of the TL001 and TL002 test groups. The sample solution at a dose of 150 mg / kg was administered orally. The body weight was weighed before administration every day, and the animal reaction was observed after administration, and the tumor volume was measured and calculated. The administration was continued for 19 days. The animals were killed 3 days after the last administration, and the tumors were weighed and dissected, and the tumor mass was weighed and converted to tumor inhibition rate.
[0099] 11. Test results
[0100] See Table 3 and Table 4. Figure 1 , Figure 2 , Figure 3 .
[0101] Table 3 shows that the tumor volume of TL001 animals did not change much compared with the blank group, while the tumor volume of TL002 animals decreased significantly compared with the blank group. Table 4 shows that the tumor weight of TL001 animals decreased slightly compared with the blank group, while the tumor volume of TL002 animals decreased significantly compared with the blank group. Figure 1 , Figure 2 , Figure 3It can be seen that the tumor volume of TL001 animals did not change significantly compared with the blank group, while the tumor volume of TL002 animals decreased significantly compared with the blank group.
[0102] Table 3 Tumor volume of animals in each group
[0103]
[0104]
[0105] Table 4 Tumor inhibition rate of TL001 and TL002 compounds
[0106]
[0107] Note: Tumor inhibition rate (%) = (tumor weight of blank group - tumor weight of experimental group) / tumor weight of blank group × 100%
[0108] 12. Result Evaluation
[0109] The dosage of TL001 compound was 150mg / kg, and the tumor inhibition rate was 6.47%; the dosage of TL002 compound was 150mg / kg, and the tumor inhibition rate was 33.39%. Both TL001 and TL002 had certain tumor inhibition rates, and the tumor inhibition rate of TL002 was significantly better than that of TL001.
Claims
1. 2'-Deoxy-2'-fluoro-4'-azido-adenosine N 6 -Acyl substituted compound, characterized in that It has the following structural formula I: Where R is C1-C 10 Straight or branched chain alkanes.
2. 2'-deoxy-2'-fluoro-4'-azido-adenosine N according to claim 1 6 -Acyl substituted compound, characterized in that At least one of the following compounds: 。 3. 2'-deoxy-2'-fluoro-4'-azido-adenosine N according to claim 1 or 2 6 -Application of acyl substituted compounds in the preparation of anti-tumor drugs.
4. 2'-deoxy-2'-fluoro-4'-azido-adenosine N according to claim 1 or 2 6 -Application of acyl substituted compounds in the preparation of anti-liver cancer drugs.