5-Azacytidine
5-Azacytidine
CAS: 320-67-2
Molecular Formula: C8H12N4O5
5-Azacytidine - Names and Identifiers
| Name | 5-Azacytidine |
| Synonyms | 5-AC 5 AZC 5-AZAC 5-AZCR u18496 u 18496 mylosar wr 183027 nci-c01569 nsc-102816 Azacitidine ladakamycin Mylosar-15N4 5-Azacytidine NSC 102816-15N4 Azacitidine-15N4 LadakaMycin-15N4 LedakaMycin-15N4 Azacytidine-15N4 antibioticu18496 NSC 103-627-15N4 Antibiotic u 18496 Antibiotic U 18496-15N4 4-amino-1-pentofuranosyl-1,3,5-triazin-2(1H)-one 4-amino-1-beta-d-ribofuranosyl-s-triazin-2(1h)-on 4-amino-1-D-lyxofuranosyl-1,3,5-triazin-2(1H)-one 4-amino-1-beta-D-ribofuranosyl-s-triazin-2(1H)-one 5-triazin-2(1h)-one,4-amino-1-beta-d-ribofuranosyl-3 4-amino-1-beta-D-ribofuranosyl-1,3,5-triazin-2(1H)-one 4-Amino-1-(beta-D-ribofuranosyl)-1,3,5-triazin-2(1H)-one |
| CAS | 320-67-2 |
| EINECS | 206-280-2 |
| InChI | InChI=1/C8H12N4O5/c9-7-10-2-12(8(16)11-7)6-5(15)4(14)3(1-13)17-6/h2-6,13-15H,1H2,(H2,9,11,16)/t3-,4+,5+,6?/m1/s1 |
| InChIKey | NMUSYJAQQFHJEW-WGDKFINWSA-N |
5-Azacytidine - Physico-chemical Properties
| Molecular Formula | C8H12N4O5 |
| Molar Mass | 244.2 |
| Density | 1.4287 (rough estimate) |
| Melting Point | 226-232°C (dec.)(lit.) |
| Boling Point | 387.12°C (rough estimate) |
| Specific Rotation(α) | 40 º (C=1, H2O 22 ºC) |
| Flash Point | 277°C |
| Water Solubility | 0.5-1.0 g/100 mL at 21 ºC |
| Solubility | Soluble in 10mg/ml 1M hydrochloric acid water. |
| Vapor Presure | 1.18E-13mmHg at 25°C |
| Appearance | White to white-like powder |
| Color | White to Off-white |
| Merck | 14,887 |
| BRN | 620461 |
| pKa | 13.46±0.70(Predicted) |
| Storage Condition | -20°C |
| Stability | Stable for 2 years from date of purchase as supplied. Solutions in DMSO or distilled water may be stored at -20° for up to 1 month. |
| Sensitive | Easily absorbing moisture |
| Refractive Index | 1.6590 (estimate) |
| MDL | MFCD00006539 |
| Physical and Chemical Properties | This product is a pyrimidine nucleoside analog produced by microbial strep toverticilium ladakanus, and can also be synthesized by chemical methods. It is a cell cycle-specific drug acting on S phase, which can rapidly phosphorylate and incorporate RNA and DNA to inhibit protein synthesis by disrupting the smooth translation of nucleic acid into protein. Pyrimidine synthesis can also be affected by inhibition of orotate nucleotide decarboxylase. |
| Use | Antimetabolites. The primary indication is acute myeloid leukemia that does not respond to conventional therapy. Also used for breast cancer, melanoma, colon cancer, etc. The main toxicities were leukopenia, thrombocytopenia and anemia. Nausea and Vomit are common adverse reactions, which can be improved by long-term continuous infusion, or with antiemetics 24h to 48h before treatment. Other toxic effects were Diarrhea, neuromuscular disturbances, Fever, hypotension and rash. The formulations were freshly formulated 3-4H before use. |
5-Azacytidine - Risk and Safety
| Hazard Symbols | T - Toxic |
| Risk Codes | R45 - May cause cancer R46 - May cause heritable genetic damage R22 - Harmful if swallowed |
| Safety Description | S53 - Avoid exposure - obtain special instructions before use. S22 - Do not breathe dust. S36/37/39 - Wear suitable protective clothing, gloves and eye/face protection. S45 - In case of accident or if you feel unwell, seek medical advice immediately (show the label whenever possible.) |
| WGK Germany | 3 |
| RTECS | XZ3017500 |
| FLUKA BRAND F CODES | 10-23 |
| HS Code | 29349990 |
| Toxicity | LD50 in mice (mg/kg): 115.9 i.p.; 572.3 orally (Palm, Kensler) |
5-Azacytidine - Nature
Open Data Verified Data
This product is a pyrimidine nucleoside analog produced by microorganism Streptoverticil-lium ladakan,us, and can also be synthesized by chemical methods. It is rapidly phosphorylated and binds to RNA and DNA by disrupting the smooth translation of nucleic acids into proteins, while inhibiting protein synthesis. In addition, it affects the synthesis of pyrimidine by inhibiting orotate nucleotide decarboxylase. It is a cell cycle-specific drug that acts on the S phase. Molecular weight 244. 21.
Last Update：2024-01-02 23:10:35
5-Azacytidine - Introduction
Zacitidine is a hypomethylated DNA methyltransferase inhibitor (DMT1) drug. This product is a cell cycle specific drug acting on the S phase. It can quickly phosphorylate and incorporate RNA and DNA into the protein by destroying nucleic acid and inhibiting protein synthesis. It can also affect the synthesis of pyrimidine by inhibiting orotate nucleotide decarboxylase.
Last Update：2022-10-16 17:24:34
5-Azacytidine - Use
Open Data Verified Data
- antimetabolites. The main indication is acute myeloid leukemia that does not respond to conventional therapy. Also used for breast cancer, melanoma, colon cancer, etc.
- usage and dose of intravenous injection, 1.0~2.2mg per kilogram of body weight, continuous infusion for 5 days.
Last Update：2022-01-01 11:12:45
5-Azacytidine - Safety
Open Data Verified Data
dose-limiting toxicity is mainly hematologic and is often manifested by leukopenia, thrombocytopenia, and anemia. Nausea and Vomit are common and can be severe and long. The symptoms may be improved by prolonged continuous infusion. Antiemetics may be helpful 24-48h before treatment. Other toxic effects were Diarrhea, neuromuscular disturbances, Fever, hepatotoxicity, hypotension and rash. The preparation was freshly prepared 3-4H before use.
Last Update：2022-01-01 11:12:45
5-Azacytidine - Reference Information
| (IARC) carcinogen classification | 2A (Vol. 50) 1990 |
| EPA chemical information | Information provided by: ofmpub.epa.gov (external link) |
| Overview | Azacitidine (azacitidine), the chemical name is 1-(β-D-furanosyl)-4-amino -1,3, 5-Triazine -2(1H)-one, also known as 5-azacytidine, azacitidine, trade name Vidaza, is a white needle-like crystal; it is a DNA methyltransferase inhibitor developed by American Pharmion Company. It was first listed in the United States in July 2004; it is a cell cycle specific drug acting on the S phase, which can quickly phosphorylate and penetrate into RNA (ribonucleic acid) and DNA (Deoxyribonucleic acid) can smoothly translate into protein by destroying nucleic acid, and inhibit protein synthesis, and can also affect pyrimidine synthesis by inhibiting orotic acid nucleotide decarboxylase; clinically, it is mainly used to treat myelodysplastic syndrome, including refractory anemia, refractory anemia with ring-shaped sideroblastoma, such as neutropenia, thrombocytopenia or blood transfusion, refractory anemia with increased primordial cells, refractory anemia with 5 subtypes of chronic myelomonocytic leukemia. |
| preparation method | 1.(1) synthesis of N-trimethylsilyl -4-trimethylsilyl -2-amine -1,3,5-triazine (intermediate I) was added to a 5 L four-mouth bottle HMDS 1 L,5-azacytosine 200g, ammonium sulfate 20g, heated and refluxed for 24 h, the system is changed into a clear solution, the temperature is reduced to 60 ℃, 1,2-dichloroethane 2 L is added to 80 ℃, the reaction is stirred for 8 h, the reaction is completed, the temperature is cooled to 5~10 ℃, and the temperature is set aside. (2) Synthesis of 1-(2,3,5-tri-O-acetyl-β-D-furanosyl)-4-amino -1,3,5-triazine -2(1H) ketone (intermediate II) 680g of tetraacetyl ribose is added to the reaction system in the next step, 200mL of trimethylsilyl trifluoromethanesulfonate is slowly added dropwise, reaction is carried out at room temperature for 12h, and the reaction solution is poured into the ice-water mixture, adjust the pH value to 7~8 with sodium hydroxide solution, extract methyl tert-butyl ether for 3 times, 600mL each time, wash the organic phase with saturated salt water for 2 times, 300mL each time, combine the organic phase, concentrate, and obtain 900g of yellow viscous substance. The mass fraction measured by HPLC was 94.9%. (3) Synthesis of Azacitidine Transfer the above viscous substance to a 3 L four-mouth bottle with 2 L methanol, add 30g of freshly prepared sodium methoxide, stir overnight at room temperature, and filter to obtain 272g of white solid, melting point 228~230 ℃, and recrystallize with pyridine to obtain 256g of white solid. Fig. 1 shows the synthesis route of azacitidine 2.(1) preparation of intermediate 2 hexamethyldisilamide 7.5L(35.3mol), 5-azacytosine (intermediate 1) 500.0g(4.5mol) and ammonium sulfate 13.0g( 0.1mol) are placed in a reaction bottle, mechanically stirred, and heated. Keep the temperature of the reaction solution 140~145 ℃ overnight. The next day, the temperature of the reaction solution was reduced to about 70 ℃, and 1050.0g of intermediate class 2 white solid was obtained by concentration under reduced pressure with 92% yield. Intermediate 2 is directly used in the next reaction without purification. (2) Preparation of Intermediate 4 Intermediate 2, tetraacetylfuranosaccharide (intermediate 3) 470. 0g (1. 5mol) and dichloromethane 3.0L obtained in the previous step were stirred in a reaction bottle. 380.0g (1.7mol) of trimethylsilyl trifluoromethanesulfonate was added within 10min, and the temperature of the reaction solution was kept no more than 25 ℃. After stirring at room temperature for 10min, the temperature is raised to 50~55 ℃ and the temperature is maintained for 2h, and the basic reaction of intermediate 3 is completed. Pour the reaction solution into 6.0L ice water containing 500.0g(3.6mol) of potassium carbonate, stir vigorously for 10min, precipitate colloidal solid, and spread diatomite for filtration. The filtrate was extracted with dichloromethane (5.0L × 3), combined with organic phase, washed with saline 3.0L, and separated. The aqueous phase was backextracted with dichloromethane 5.0L. Combine the organic phase, dry with anhydrous magnesium sulfate 1.5kg, filter, and add silica gel 1.5kg to concentrate to completely dry the solvent. Column chromatography: The mobile phase is ethyl acetate first, and then V (ethyl acetate): V (methanol) = 20: 1 solution. 3600.0g of intermediate 4 was obtained, and the yield was 55% (calculated as intermediate 3). (3) Preparation of Azacitidine 360.0g(0.8mol) of intermediate 4 was dissolved in 3.3L of methanol solution containing 10.0g(0.19mol) of sodium methoxide, stirred and dissolved, and a large amount of solid was precipitated after 30min. Stirring for 48 hours, HPLC detected that the raw material reaction was complete (raw material residence time = 16.3min, product residence time = 9.6min, chromatographic column: C18,4.6mm × 150mm; Mobile phase: methanol/water, methanol 0min (30% )~ 15min(60%), operation 40min). Filtration, solid washing with methanol 1.0L, vacuum drying at 70 ℃ overnight to obtain azacitidine finished product. Fig. 2 shows the synthetic route of azacitidine |
| pharmacological action | azacitidine exerts its anti-tumor effect by reducing the methylation process of DNA and producing direct cytotoxicity to abnormal hematopoietic cells of bone marrow. In vitro studies have shown that this product can inhibit the concentration of D NA methylation to the greatest extent and will not seriously hinder DNA synthesis. Hypomethylation can restore normal function of genes closely related to cell differentiation and proliferation. The cytotoxic effect of this product can cause the death of rapidly proliferating cells, including those cancer cells that have lost the control of normal mechanisms, while non-proliferating cells are relatively insensitive to this product. (2015-12-21) |
| pharmacodynamic | this product may be metabolized by liver, and whether it is affected by microsomal enzyme inhibitors and inducers is unknown. This product will not induce CYP1A2,2C19 and 3A4 /5 at an in vitro concentration of 1~100 μmol · L-1. The possibility of cytochrome P450 enzyme inhibition is unknown. After intravenous administration of isotope-labeled drugs in 5 patients, it was found that the cumulative urinary excretion rate of prototype drugs and their metabolites was 58%, and less than 1% in feces. The elimination half-life of total radioactivity after intravenous and subcutaneous injection is about 4h. |
| application | this product is used to treat the following subtypes of myelodysplasia syndrome: refractory anemia (RA), annular sideroblastic refractory anemia (RARS) (with neutropenia or thrombocytopenia or requiring blood transfusion), refractory anemia with increased primordial cells (RAEB), refractory anemia with increased primordial cells (RAEB-T) and chronic myelomonocytic leukemia (CMMoL). |
| adverse reactions | common nausea, anemia, thrombocytopenia, vomiting, fever, leukopenia, diarrhea, fatigue, pain at the injection site and erythema, constipation, neutropenia, spots, cough, headache, dizziness, arthralgia, anorexia, pharyngitis, etc. Rare serum myointoxication, renal failure, renal tubular acidosis, hypokalemia, hepatic coma, dyspnea, chills, limb pain, back pain, pharyngitis, edema, chest pain, abdominal pain, rash, anxiety, heart failure, etc. |
| precautions | 1. this product is related to neutrophil and thrombocytopenia. some patients reduce or stop taking medicine due to thrombocytopenia, neutropenia and leukopenia. 2. This product and its metabolites are mainly excreted by the kidneys. Patients with renal insufficiency have greater toxicity when using this product; it has potential liver toxicity for patients with severe liver insufficiency. Therefore, close check blood before and during each course of treatment And liver and kidney function. 3. Whether the drug is excreted from milk is still unknown, and women receiving this product should not breastfeed. 4. Animal experiments prove that this product can cause tumors and stillbirth, and the fetus may be harmed when pregnant women use this product. The safety of medication during pregnancy was classified as grade D. During the use of this product, women are advised to avoid pregnancy. Because this product will affect the vitality of sperm, male patients should also take contraceptive measures. 5. If you accidentally splash this product on your skin, rinse it with plenty of water immediately. 6. This product must be used within lh after dissolution. If it is not used immediately, it should be placed in the refrigerator (2~8 ℃) for no more than 8 h. Take it out of the refrigerator and leave it at room temperature for 30min before use. In order to avoid the deposition of suspension in the syringe, the syringe should be gently shaken for 30s before injection. 7. It is known to be allergic to this product or mannitol, and it is prohibited for patients with advanced malignant liver cancer. |
| use | antimetabolites. The main indication is acute myeloid leukemia that does not respond to conventional treatment. It is also used for breast cancer, melanoma, bowel cancer, etc. Toxicity is mainly manifested by leukopenia, thrombocytopenia and anemia. Nausea and vomiting are common adverse reactions, which can be improved by long-term continuous infusion, or antiemetic 24 to 48 hours before treatment. Other toxic effects are diarrhea, neuromuscular disorders, fever, hypotension and rash. The preparation was freshly prepared 3-4h before use. A powerful growth inhibitor and cytotoxin agent, inhibiting DNA methyltransferase, an important regulatory mechanism of gene expression, gene activation and silencing; cancer-making aid, with weak antibody activity (Gram positive); used to study the DNA methylation process, DNA combined molecular effect a potential growth inhibitor and cytotoxin vector; Inhibition of DNA methyltransferase, the enzyme is an important mechanism for regulating gene expression, gene activation and gene shutdown. This factor causes DNA demethylation or semi-demethylation, allowing transcription factors to bind to DNA and reactivate tumor suppressor genes. |
| category | toxic substances |
| toxicity classification | highly toxic |
| acute toxicity | oral administration-mouse LD50: 572 mg/kg; Abdominal cavity-mouse LD50: 68 mg/kg |
| flammability hazard characteristics | flammability; Combustion produces toxic nitrogen oxide smoke; Side effects of patient medication: nausea, vomiting, diarrhea, leukopenia |
| storage and transportation characteristics | ventilation and low temperature drying; separate from warehouse food raw materials |
| fire extinguishing agent | dry powder, foam, sand, carbon dioxide, mist water |
| toxic substance data | information provided by: pubchem.ncbi.nlm.nih.gov (external link) |
Last Update：2024-04-09 19:05:11
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View History
5-Azacytidine
对叔丁基环己醇(薄醇)
3-Nitroacetophenone
4-N-叔丁氧羰基-哌嗪-2-羧酸
烯丙基[1,3-双(2,4,6-三甲苯基)咪唑-2-亚基]氯化钯(II)
1-BUTYL-3-METHYLIMIDAZOLIUM NITRATE
Fumaric acid diethyl ester
2-Hydroxy-6-methylnicotinic acid
ETHYL (DIPHENYLMETHYLENAMINO)ACETATE
5,6-Dibromobenzo[d]thiazol-2-amine
对叔丁基环己醇(薄醇)
3-Nitroacetophenone
4-N-叔丁氧羰基-哌嗪-2-羧酸
烯丙基[1,3-双(2,4,6-三甲苯基)咪唑-2-亚基]氯化钯(II)
1-BUTYL-3-METHYLIMIDAZOLIUM NITRATE
Fumaric acid diethyl ester
2-Hydroxy-6-methylnicotinic acid
ETHYL (DIPHENYLMETHYLENAMINO)ACETATE
5,6-Dibromobenzo[d]thiazol-2-amine