Azacitidine

Base Information

• Chemical Name: Azacitidine
• CAS No.: 320-67-2
• Molecular Formula: C8H12N4O5
• Molecular Weight: 244.207
• Hs Code.: 29349990
• European Community (EC) Number: 206-280-2
• NSC Number: 758186
• UNII: M801H13NRU
• DSSTox Substance ID: DTXSID9020116
• Nikkaji Number: J1.523G
• Wikipedia: Azacitidine
• Wikidata: Q416451
• NCI Thesaurus Code: C288
• RXCUI: 1251
• Pharos Ligand ID: APQ4TYS6L28M
• Metabolomics Workbench ID: 43193
• ChEMBL ID: CHEMBL1489
• Mol file: 320-67-2.mol

Synonyms:5 Azacytidine;5-Azacytidine;Azacitidine;Azacytidine;NSC 102816;NSC-102816;NSC102816;Vidaza

Chemical Property of Azacitidine

Chemical Property:

• Appearance/Colour: White-to-off-white crystalline solid
• Vapor Pressure: 1.18E-13mmHg at 25°C
• Melting Point: 226-232 °C (dec.)(lit.)
• Refractive Index: 1.823
• Boiling Point: 534.5 °C at 760 mmHg
• PKA: 13.46±0.70(Predicted)
• Flash Point: 277 °C
• PSA: 143.72000
• Density: 2.08 g/cm³
• LogP: -2.58680
• Storage Temp.: 2-8°C
• Solubility.: Soluble in DMSO (up to 25 mg/ml), or in Water (up to 12 mg/ml).
• Water Solubility.: 0.5-1.0 g/100 mL at 21 ºC
• XLogP3: -2.2
• Hydrogen Bond Donor Count: 4
• Hydrogen Bond Acceptor Count: 5
• Rotatable Bond Count: 2
• Exact Mass: 244.08076950
• Heavy Atom Count: 17
• Complexity: 384

Purity/Quality:

99% ,99.9%, ^*data from raw suppliers

5-Azacytidine 98+% ^*data from reagent suppliers

Safty Information:

• Pictogram(s): T
• Hazard Codes: T
• Statements: 45-46-22
• Safety Statements: 53-22-36/37/39-45

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Antineoplastic Agents
• Canonical SMILES: C1=NC(=NC(=O)N1C2C(C(C(O2)CO)O)O)N
• Isomeric SMILES: C1=NC(=NC(=O)N1[C@H]2[C@@H]([C@@H]([C@H](O2)CO)O)O)N
• Recent ClinicalTrials: Study of Efficacy and Safety of MBG453 in Combination With Azacitidine in Subjects With Intermediate, High or Very High Risk Myelodysplastic Syndrome (MDS) as Per IPSS-R, or Chronic Myelomonocytic Leukemia-2 (CMML-2)
• Recent EU Clinical Trials: Venetoclax plus Azacitidine versus Standard intensive Chemotherapy for Patients with newly diagnosed Acute Myeloid Leukemia (AML) and NPM1 Mutations eligible for intensive Treatment (VINCENT)
• Recent NIPH Clinical Trials: [M20-866] AML and MDS: Lemzoparlimab in Combination with Venetoclax and/or Azacitidine
• Description: Azacytidine also referred to as Azacytidine and 5-azacytidine (brand name: Vidaza) is an anti-cancer chemotherapy medication. The drug is classified as demethylation and antimetabolite agent. Azacytidine acts by inhibiting the growth and proliferation of cancer cells in the body. The drug is indicated for the treatment of specific types of blood cell disorders and bone marrow cancers. 5-Azacytidine is an analog of the nucleoside cytidine which can be incorporated into DNA and RNA. 5-Azacytidine acts as an epigenetic modifier by incorporating into DNA where it irreversibly binds to DNA methyltransferases, thus inhibiting their activity.Azacitidine is an antineoplastic agent launched for the treatment of myelodysplastic syndrome (MDS). MDS is a group of closely related diseases caused by abnormal blood-forming stem cells of the bone marrow. Azacitidine is indicated for the treatment of all five subtypes of MDS, which consist of refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, and chronic myelomonocytic leukemia.
• Uses: A potent growth inhibitor and cytotoxic agent. It acts as a demethylating agent by inhibiting DNA methyltransferase Antineoplastic;'Antimetabolite 5-Azacytidine, its incorporation into RNA alters RNA synthesis and processing, and results in inhibition of protein synthesis. It has been used as a cancer chemotherapeutic agent. It is a powerful bacteriostatic, antitumor, and mutagenic agent; it also exhibits immunosuppressive, antimitotic, radioprotective, and virostatic effects.
• Therapeutic Function: Antineoplastic
• Biological Functions: Azacitidine is given subcutaneously for the treatment of myelodysplastic syndrome, and serum levels generally are maximized within 30 minutes. The parent drug and its metabolites are excreted in the urine. Azacitidine is carcinogenic and teratogenic in rodents, and leukopenia, thrombocytopenia, and neutropenia are the most common reasons for drug discontinuation or dosage reduction.
• Clinical Use: Antineoplastic agent: Treatment of people not eligible for stem cell transplants with myelodysplastic syndromes, chronic myelomonocytic leukaemia or acute myeloid leukaemia
• Drug interactions: Potentially hazardous interactions with other drugs None known

Technology Process of Azacitidine

There total 22 articles about Azacitidine which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 99.13%

5-azacytidine mono-hydrochloride → 5-azacytidine (320-67-2)

Guidance literature:

With triethylamine; In methanol; at 25 - 30 ℃; for 2h; Product distribution / selectivity; Inert atmosphere;

Reference yield: 89.2%

p-chlorobenzoyl azacitidine → 5-azacytidine (320-67-2)

Guidance literature:

With ammonia; In methanol; for 2h;

Reference yield: 80.2%

2,3,5-tri-O-acetyl-β-D-ribofuranose-4-amino-1,3,5-triazine (10302-78-0) → 5-azacytidine (320-67-2)

Guidance literature:

With sodium methylate; In methanol; for 2h; Inert atmosphere;

upstream raw materials:

N-(Formylamidino)-N'-β-D-ribofuranosylharnstoff

1,2,3,5-tetraacetylribose

2-(trimethylsilylamino)-4-(trimethylsilyloxy)-s-triazine

2,3,5-tri-O-acetyl-β-D-ribofuranose-4-amino-1,3,5-triazine

Downstream raw materials:

5'-O-(4,4'-dimethoxytrityl)-5-azacytidine

5,6-dihydro-5-azacytidine

2’, 3’-O-isopropyl-5-N-cytidine

Imidazole-1-carbothioic acid O-{(2R,3R,5S)-2-(4-amino-2-oxo-2H-[1,3,5]triazin-1-yl)-5-[bis-(4-methoxy-phenyl)-phenyl-methoxymethyl]-tetrahydro-furan-3-yl} ester

Refernces

• 1、 Bozhok,Kalinichenko,Kuz’mitskii,Golubeva. "Synthesis, Hydrolytic Stability, and Antileukemic Activity of Azacytidine Nucleoside Analogs". . p. 804 - 809. Retrieved 2016.
• 2、 -. "Method for preparing azacitidine by high-purity and low-calcination residue". Paragraph 0014; 0043; 0046-0048; 0051-0053; 0056-0058;. . Retrieved 2019/10/01.
• 3、 -. "Preparation method of azacitidine (by machine translation)". Paragraph 0024; 0027; 0028; 0031; 0032; 0035; 0036; 0039. . Retrieved 2019/10/01.