Clofarabine

Base Information

• Chemical Name: Clofarabine
• CAS No.: 123318-82-1
• Molecular Formula: C10H11ClFN5O3
• Molecular Weight: 303.68
• Hs Code.: 29349990
• European Community (EC) Number: 631-422-9
• UNII: 762RDY0Y2H
• DSSTox Substance ID: DTXSID5046437
• Nikkaji Number: J457.798A
• Wikipedia: Clofarabine
• Wikidata: Q5134875
• NCI Thesaurus Code: C26638
• RXCUI: 44151
• Pharos Ligand ID: BZGNRY23MQGT
• Metabolomics Workbench ID: 42955
• ChEMBL ID: CHEMBL1750
• Mol file: 123318-82-1.mol

Synonyms:2 Chloro 2' arabino fluoro 2' deoxyadenosine;2 Chloro 2' fluoroarabino 2' deoxyadenosine;2-chloro-2'-arabino-fluoro-2'-deoxyadenosine;2-chloro-2'-fluoroarabino-2'-deoxyadenosine;2-chloro-9-(2-deoxy-2-fluoro-beta-D-arbinofuranosyl)adenine;2-chloro-9-(2-deoxy-2-fluoroarabinofuranosyl)adenine;9H-Purin-6-amine, 2-chloro-9-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-;Cl-F-ara-A;clofarabine;Clofarex;Clolar;Evoltra

Chemical Property of Clofarabine

Chemical Property:

• Appearance/Colour: white solid
• Vapor Pressure: 3.19E-15mmHg at 25°C
• Melting Point: 228-231 °C
• Refractive Index: 1.843
• Boiling Point: 550 °C at 760 mmHg
• PKA: 12.56±0.70(Predicted)
• Flash Point: 286.4 °C
• PSA: 119.31000
• Density: 2.12 g/cm³
• LogP: 0.23180
• Storage Temp.: Desiccate at +4°C
• Solubility.: DMSO: >10mg/mL
• XLogP3: 0.9
• Hydrogen Bond Donor Count: 3
• Hydrogen Bond Acceptor Count: 8
• Rotatable Bond Count: 2
• Exact Mass: 303.0534451
• Heavy Atom Count: 20
• Complexity: 370

Purity/Quality:

99% ^*data from raw suppliers

Clofarabine ^*data from reagent suppliers

Safty Information:

• Pictogram(s): T
• Hazard Codes: T
• Statements: 25
• Safety Statements: 45

MSDS Files:

SDS file from LookChem

Total 1 MSDS from other Authors

Useful:

• Drug Classes: Antineoplastic Agents
• Canonical SMILES: C1=NC2=C(N=C(N=C2N1C3C(C(C(O3)CO)O)F)Cl)N
• Isomeric SMILES: C1=NC2=C(N=C(N=C2N1[C@H]3[C@H]([C@@H]([C@H](O3)CO)O)F)Cl)N
• Recent ClinicalTrials: Cord Blood Transplant in Children and Young Adults With Blood Cancers and Non-malignant Disorders
• Recent EU Clinical Trials: A Phase Ib study of Vyxeos? (liposomal daunorubicin and cytarabine) in combination with Clofarabine in children with relapsed/refractory AML, ITCC-092
• Description: Clofarabine is a new member of the purine nucleoside antimetabolite class of drugs, and it was launched as an intravenous infusion for treating pediatric patients (1–21 years old) with relapsed or refractory acute lymphoblastic leukemia (ALL) after at least two prior regimens. Adenosine-related antimetabolites, such as cladribine and fludarabine have proven successful in treating low-grade lymphomas, chronic lymphocytic leukemia, and hairy-cell leukemia. Although structurally similar to cladribine and fludarabine, a key differentiator for clofarabine is the presence of a fluorine in the C-2′ position, which renders it less susceptible to phosphorolytic cleavage of the glycosydic bond and inactivation by purine nucleoside phosphorylases. In addition, the C-2′ fluoro group improves the acid stability relative to its predecessors. As seen with other purine nucleoside analogs, the mechanism of action of clofarabine involves intracellular phosphorylation to active triphosphate by 2′ -deoxycytidine kinase, and subsequent inhibition of RNA reductase and DNA polymerase a. Clofarabine is cytotoxic to rapidly proliferating and quiescent cancer cell types in vitro.The higher potency of clofarabine relative to other purine nucleoside analogs is attributed to the higher efficiency of its phosphorylation by deoxycytidine kinase, and the longer intracellular half-life of the triphosphate metabolite (＞24 h). The chemical synthesis of clofarabine involves the conversion of 2-deoxy-2-β-fluoro-1,3,5-tri-O-benzoyl- 1-α-D-arabinofuranose to the corresponding bromosugar with hydrogen bromide, subsequent coupling with 2-chloroadenine, and the removal of benzoyl protecting groups with catalytic sodium methoxide in methanol. The recommended pediatric dosage of clofarabine is 52mg/m2 daily, administered by i.v. infusion over 2 h, for 5 consecutive days. Treatment cycles are repeated following recovery or return to baseline organ function, approximately every 2–6weeks.Clinical efficacy of clofarabine was evaluated in a single-arm study involving 49 pediatric patients, who had relapsed or failed two or more prior therapies. Fifteen patients (30.6%) demonstrated either a complete remission, a complete remission minus platelet recovery, or a partial response. For patients experiencing complete remission, the response lasted from 43 days to ＞160 days. Adverse events associated with clofarabine were similar to other chemotherapy agents, including vomiting, nausea, febrile neutropenia, and diarrhea.
• Uses: Clofarabine has been used in a cell viability assay to analyze the sensitivity of the isogenic cell lines towards clofarabine. It is also used to study the interaction of anticancer drug clofarabine with human serum albumin and human α-1 acid glycoprotein. ISecond generation purine nucleoside analog; antimetabolite that inhibits DNA synthesis and resists deamination by adenosine deaminase. Antineoplastic

Technology Process of Clofarabine

There total 25 articles about Clofarabine 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: 95.5%

6-amino-2-chloro-9-(2'-deoxy-2'-fluoro-3',5'-di-O-benzoyl-β-D-arabinofuranosyl)-9H-purine (355138-50-0) → clofarabine (123318-82-1)

Guidance literature:

With methanol; sodium methylate; at 15 - 20 ℃; for 2h;

Reference yield: 90.0%

6-amino-2-chloro-9-(2-deoxy-2-fluoro-3,5-di-O-(triisopropylsilyl)-β-D-arabinofuranosyl)-9H-purine (1234346-14-5) → clofarabine (123318-82-1)

Guidance literature:

With tetramethylammonium fluoride; acetic acid; In N,N-dimethyl-formamide; at 20 ℃;

Reference yield: 90.0%

C25H19ClF3N5O8S → clofarabine (123318-82-1)

Guidance literature:

With ammonia; In methanol; at 60 ℃; for 5h;

DOI:10.1039/c6ra27790j

upstream raw materials:

2,6-dichloro-9-(3-O-acetyl-5-O-benzoyl-2-deoxy-2-fluoro-β-D-arabinofuranosyl)-9H-purine

6-amino-2-chloro-9-(2'-deoxy-2'-fluoro-3',5'-di-O-benzoyl-β-D-arabinofuranosyl)-9H-purine

1,3,5-tri-O-benzoyl-2-deoxy-2-fluoro-α-D-arabinofuranose

9-Trimethylsilyl-2,6-dichlorpurin

Downstream raw materials:

C₄₅H₇₇ClFN₅O₁₀P^(1-)*Na⁽¹⁺⁾

Refernces

• 1、 -. "Green synthesizing technology of clofarabine". Paragraph 0004; 0028-0032. . Retrieved 2019/02/25.
• 2、 -. "Method for synthesizing clofarabine". Paragraph 0040; 0067; 0068. . Retrieved 2017/08/27.