Fludarabine

Base Information

• Chemical Name: Fludarabine
• CAS No.: 21679-14-1
• Molecular Formula: C₁₀H₁₂FN₅O₄
• Molecular Weight: 285.235
• Hs Code.: 29349990
• European Community (EC) Number: 244-525-5
• UNII: P2K93U8740
• DSSTox Substance ID: DTXSID4039657
• Nikkaji Number: J33.087F
• Wikipedia: Fludarabine
• Wikidata: Q72478349
• NCI Thesaurus Code: C1094
• RXCUI: 24698
• Pharos Ligand ID: B6JBTYSCP6RL
• ChEMBL ID: CHEMBL1568
• Mol file: 21679-14-1.mol

Synonyms:2-fluoroadenine arabinoside;9-beta-D-arabinofuranosyl-2-fluoroadenine;9H-purin-6-amine, 9-beta-D-arabinofuranosyl-2-fluoro-;F-ara-A;fludarabine

Chemical Property of Fludarabine

Chemical Property:

• Appearance/Colour: white solid
• Vapor Pressure: 1.86E-23mmHg at 25°C
• Melting Point: 265-268 °C
• Refractive Index: 1.876
• Boiling Point: 747.3 °C at 760 mmHg
• PKA: 13.05±0.70(Predicted)
• Flash Point: 405.8 °C
• PSA: 139.54000
• Density: 2.17 g/cm³
• LogP: -1.25970
• Storage Temp.: 2-8°C
• Solubility.: DMF: 20 mg/mL, clear, faintly yellow
• Water Solubility.: Soluble in DMF, DMSO, methanol or ethanol. Sparingly soluble in water
• XLogP3: -0.6
• Hydrogen Bond Donor Count: 4
• Hydrogen Bond Acceptor Count: 9
• Rotatable Bond Count: 2
• Exact Mass: 285.08733204
• Heavy Atom Count: 20
• Complexity: 367

Purity/Quality:

99% ^*data from raw suppliers

Fludarabine ^*data from reagent suppliers

Safty Information:

• Pictogram(s): R23/24/25:; R36/37/38:; R39:
• Hazard Codes: Xn
• Statements: 23/24/25-36/37/38-39/23/24/25-39-22
• Safety Statements: 26-36/37-45-36

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Antineoplastic Agents
• Canonical SMILES: C1=NC2=C(N=C(N=C2N1C3C(C(C(O3)CO)O)O)F)N
• Isomeric SMILES: C1=NC2=C(N=C(N=C2N1[C@H]3[C@H]([C@@H]([C@H](O3)CO)O)O)F)N
• Recent ClinicalTrials: Immunotherapy Using Tumor Infiltrating Lymphocytes for Patients With Metastatic Cancer
• Recent EU Clinical Trials: Phase I/IIa multicentre phase I/IIa study of infusion of autologous peripheral blood T lymphocytes expanded and genetically modified using Sleeping Beauty family transposons to express a chimeric antigenic receptor with anti-CD19 specificity conjugated to the 4-1BB co-stimulatory and signal-transduction region CD3z and huEGFRt (TranspoCART19) in patients with relapsed or refractory B-cell lymphoma.
• Recent NIPH Clinical Trials: Multi-institutional phase 1 clinical study to examine the safety and tolerability of MU-MA402C for MAGE A4-positive and HLA-A*02:01-positive unresectable advanced or recurrent solid cancer
• Description: Fludarabine (21679-14-1) is a synthetic adenosine analog that inhibits DNA biosynthesis and is a clinically useful antineoplastic agent.1 In cells fludarabine accumulates as its 5’-triphosphate (F-ara-ATP) for which the rate-limiting step in formation is the conversion of fludarabine to its monophosphate.2 F-ara-ATP has multiple mechanisms of action including inhibition of ribonucleotide reductase, DNA polymerase, ligase and primase.2 A frequently used agent in myeloablative conditioning regimens for allogeneic hematopoietic cell transplantation.3 Immunosuppressive effects are mediated via inhibition of TNFa-stimulated production of IL-2 and IFN-g through inactivation of NFkB.4 Antagonist at adenosine A1 receptors.5
• Uses: Fludarabine is not one of the most used drugs in pediatric oncology area. It is used in combination with other drugs to treat AML in children, mostly those who are receiving second-line therapy. It is commonly sold as 10 mg film-coated tablets and IV vial containing 50mg. Fludarabine is used in the treatment of chroniclymphocytic leukaemia. It is a DNA synthesis and methylation inhibitor;A cell permeable agent that interferes with DNA synthesis and repair; also inhibits RNA transcription.
• Indications: Fludarabine (Fludara) is a fluorinated purine analogue of the antiviral agent vidarabine.The active metabolite, 2-fluoro-ara-adenosine triphosphate, inhibits various enzymes involved in DNA synthesis, including DNA polymerase-α, ribonucleotide reductase, and DNA primase. Unlike most antimetabolites, it is toxic to nonproliferating as well as dividing cells, primarily lymphocytes and lymphoid cancer cells. The drug is highly active in the treatment of chronic lymphocytic leukemia, with approximately 40% of patients achieving remissions after previous therapy with alkylating agents has failed. Activity is also seen in the low-grade lymphomas. The major side effect is myelosuppression, which contributes to fevers and infections in as many as half of treated patients. Nausea and vomiting are mild. Occasional neurotoxicity has been noted at higher doses, with agitation, confusion, and visual disturbances.
• Therapeutic Function: Antineoplastic

Technology Process of Fludarabine

There total 20 articles about Fludarabine 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: 95.0%

2-fluoro-9-(2,3,5-tri-o-benzyl-beta-D-arabinofuranosyl)adenine (24649-69-2) → Fludarabine (146-78-1,19768-92-4,21679-14-1,21679-15-2)

Guidance literature:

2-fluoro-9-(2,3,5-tri-o-benzyl-beta-D-arabinofuranosyl)adenine; With palladium 10% on activated carbon; ammonium formate; In methanol; water; at 25 - 75 ℃; Inert atmosphere;

In water; at 90 - 95 ℃;

DOI:10.1021/op3000509

Reference yield: 93.0%

2-fluoro-9-(3,5-di-O-benzoyl-β-D-arabinofuranosyl)adenine → Fludarabine (146-78-1,19768-92-4,21679-14-1,21679-15-2)

Guidance literature:

With methanol; ammonia; at 0 - 40 ℃; for 6h; Autoclave;

DOI:10.1055/s-0039-1690732

Reference yield: 92.0%

araU (3083-77-0) + 2-fluoroadenosine (146-78-1) → Fludarabine (146-78-1,19768-92-4,21679-14-1,21679-15-2)

Guidance literature:

With uridine phosphorylase; disodium hydrogen arsenate heptahydrate; Escherichia coli purine nucleoside phosphorylase; In aq. phosphate buffer; at 52 ℃; pH=7; Enzymatic reaction;

DOI:10.1134/S1068162016040105

upstream raw materials:

fludarabine phosphate

2,3,5-tri-O-benzyl-1-(4-nitrobenzoyloxy)-D-arabinofuranose

2,3,5-tri-O-benzyl-α-D-arabinofuranosyl chloride

6-azido-2-fluoropurine

Downstream raw materials:

fludarabine phosphate

2-fluoroadenine

O¹-Phosphono-α-D-arabinofuranose

Refernces

• 1、 -. "Synthesis method of fludarabine phosphate". Paragraph 0041-0043; 0056-0060. . Retrieved 2020/08/22.
• 2、 -. "Synthesis process of fludarabine base". Paragraph 0012-0025. . Retrieved 2018/11/10.