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75607-67-9, Fludarabine Phosphate, CAS:75607-67-9

75607-67-9, Fludarabine Phosphate,
CAS:75607-67-9
C10H13FN5O7P / 365.21
MFCD00866418

 氟达拉滨磷酸盐, Fludarabine phosphate

Fludarabine phosphate is an antileukemic drug that inhibits DNA polymerase α and β, as well as other enzymes in the nucleotide synthesis pathway. It is used to treat patients with chronic myelogenous leukemia (CML) who have developed resistance to other treatments. Fludarabine phosphate has been shown to induce a cytotoxic effect against tumor cells by binding to ATP-binding cassette transporter proteins on the cell membrane and inhibiting intracellular targets such as DNA, RNA, and protein synthesis. Fludarabine phosphate has also been shown to inhibit the growth of tumor cells through synergistic interactions with other anticancer drugs such as hydroxyurea or busulfan, which may be due to its ability to inhibit enzyme activities such as erythrocyte alkaline phosphatase.

Fludarabine phosphate is a chemical compound that belongs to the purine analog class of drugs. It is an antineoplastic agent, which is used for the treatment of various cancers, particularly chronic lymphocytic leukemia (CLL) and non-Hodgkin's lymphoma (NHL). Fludarabine phosphate is a prodrug of fludarabine, which is converted to fludarabine triphosphate (FLT) by deoxycytidine kinase (dCK) in cells. FLT is a potent inhibitor of DNA synthesis and causes cell death by apoptosis. In this paper, we will discuss the physical and chemical properties, synthesis and characterization, analytical methods, biological properties, toxicity, safety, applications in scientific experiments, limitations, and future directions of fludarabine phosphate.

Physical and Chemical Properties:

The chemical formula of fludarabine phosphate is C10H13FN5O7P. It is a white or slightly yellow crystalline powder, which is soluble in water and slightly soluble in ethanol. The molecular weight of fludarabine phosphate is 365.2 g/mol. It has a melting point of 110-112°C. The pKa and log P values of fludarabine phosphate are 1.4 and -0.3, respectively.

Synthesis and Characterization:

Fludarabine phosphate can be synthesized by the reaction of 2-fluoro-ara-adenosine with phosphoric acid in the presence of sulfuric acid. The reaction yields fludarabine phosphate, which is then purified by recrystallization. The structure of fludarabine phosphate can be characterized by various spectroscopic techniques, such as nuclear magnetic resonance (NMR) spectroscopy, infrared (IR) spectroscopy, and mass spectrometry.

Analytical Methods:

Several analytical methods have been developed for the analysis of fludarabine phosphate, including High-performance liquid chromatography (HPLC), Gas chromatography (GC), Ultraviolet-visible (UV-Vis) spectrophotometry, and Capillary electrophoresis (CE). These techniques can be used to determine the purity, potency, and stability of fludarabine phosphate.

Biological Properties:

Fludarabine phosphate has potent antineoplastic activity against CLL, NHL, and other cancers. It is a DNA synthesis inhibitor, which induces cell cycle arrest and apoptosis in cancer cells. Fludarabine phosphate can also affect the immune system by reducing the number of lymphocytes and impairing their function. It has been shown to be effective in combination with other drugs, such as cyclophosphamide, rituximab, and alemtuzumab.

Toxicity and Safety in Scientific Experiments:

Fludarabine phosphate can cause various adverse effects, including myelosuppression, immunosuppression, infectious complications, autoimmune disorders, and opportunistic infections. It can also cause severe allergic reactions, liver and kidney damage, and neurological disorders. The safety of fludarabine phosphate in scientific experiments depends on its dose, duration of exposure, and route of administration. The toxicity and safety of fludarabine phosphate can be assessed by animal studies, in vitro experiments, and clinical trials.

Applications in Scientific Experiments:

Fludarabine phosphate has several applications in scientific experiments, including cancer research, immunology, pharmacology, and toxicology. It can be used to study the mechanism of action of DNA synthesis inhibitors, apoptosis inducers, and immunomodulators. Fludarabine phosphate can also be used to evaluate the efficacy and safety of new drugs, drug combinations, and drug delivery systems.

Current State of Research:

Fludarabine phosphate is currently used for the treatment of CLL, NHL, and other cancers. However, there is ongoing research on the development of new drugs and treatment strategies that can improve its efficacy and reduce its toxicity. Several clinical trials are underway to investigate the safety and efficacy of fludarabine phosphate in combination with other drugs, such as venetoclax, obinutuzumab, and daratumumab.

Future Directions:

There are several future directions for the research and development of fludarabine phosphate. These include:

1. Developing new analogs of fludarabine phosphate that have higher potency, selectivity, and safety.

2. Designing new drug delivery systems that can enhance the bioavailability and reduce the toxicity of fludarabine phosphate.

3. Investigating the molecular mechanisms of resistance to fludarabine phosphate and developing strategies to overcome it.

4. Studying the immunomodulatory effects of fludarabine phosphate and its potential use in cancer immunotherapy.

5. Developing new biomarkers to predict the response to fludarabine phosphate and to monitor its toxicity.

6. Investigating the potential use of fludarabine phosphate in other diseases, such as autoimmune disorders and viral infections.

7. Developing new methods to synthesize fludarabine phosphate that are more efficient, cost-effective, and environmentally friendly.

8. Investigating the long-term safety and efficacy of fludarabine phosphate in patients with CLL and NHL.

9. Performing pharmacokinetic studies to optimize the dosing regimen and to prevent drug interactions.

10. Studying the potential interactions of fludarabine phosphate with food, supplements, and other drugs to optimize its safety and efficacy.

Conclusion:

Fludarabine phosphate is a potent antineoplastic agent that has several applications in cancer research and treatment. It has some adverse effects that need to be carefully monitored. Future research on fludarabine phosphate should focus on developing new analogs and drug delivery systems, understanding its immunomodulatory effects, and investigating its potential use in other diseases. The ultimate goal is to improve the safety and efficacy of fludarabine phosphate and to provide better treatment options for patients with cancer and other diseases.

Title: Fludarabine

CAS Registry Number: 21679-14-1

CAS Name: 9-b-D-Arabinofuranosyl-2-fluoro-9H-purin-6-amine

Additional Names: 9-b-D-arabinofuranosyl-2-fluoroadenine; 2-fluorovidarabine; 2-fluoro-9-b-D-arabinofuranosyladenine; 2-F-araA

Manufacturers' Codes: NSC-118218; NSC-118218-H

Molecular Formula: C10H12FN5O4

Molecular Weight: 285.23

Percent Composition: C 42.11%, H 4.24%, F 6.66%, N 24.55%, O 22.44%

Literature References: Adenosine deaminase-resistant purine nucleoside antimetabolite. Prepn and in vitro cytotoxicity: J. A. Montgomery, K. Hewson, J. Med. Chem. 12, 498 (1969). Improved prepn: J. A. Montgomery et al., J. Heterocycl. Chem. 16, 157 (1979); J. A. Montgomery, US 4210745 (1980 to U.S. Dept. Health, Education and Welfare). Inhibition of DNA synthesis and in vivo antileukemic activity: R. W. Brockman et al., Biochem. Pharmacol. 26, 2193 (1977). Metabolized to 5¢-monophosphate: R. W. Brockman et al., Cancer Res. 40, 3610 (1980). HPLC determn in human leukemia cells: V. Gandhi et al., J. Chromatogr. 413, 293 (1987). Prepn of 5¢-monophosphate: J. A. Montgomery, A. T. Shortnacy, US 4357324 (1982 to U.S. Dept. of Health and Human Services). Pharmacokinetics in humans: M. R. Hersh et al., Cancer Chemother. Pharmacol. 17, 277 (1986). Evaluation of therapeutic efficacy and CNS toxicity in acute refractory leukemia: R. P. Warrell, Jr., E. Berman, J. Clin. Oncol. 4, 74 (1986); H. G. Chun et al., Cancer Treat. Rep. 70, 1225 (1986). Series of articles on pharmacology and therapeutic use: Semin. Oncol. 17, Suppl. 8, 1-78 (1990).

Properties: Crystals from ethanol + water, mp 260°. [a]D25 +17 ±2.5° (c = 0.1 in ethanol). uv max (pH 1, pH 7, pH 13): 262, 261, 262 nm (e ´ 10-3 13.2, 14.8, 15.0). Sparingly sol in water, organic solvents.

Melting point: mp 260°

Optical Rotation: [a]D25 +17 ±2.5° (c = 0.1 in ethanol)

Absorption maximum: uv max (pH 1, pH 7, pH 13): 262, 261, 262 nm (e ´ 10-3 13.2, 14.8, 15.0)

 

Derivative Type: 5'-Monophosphate

CAS Registry Number: 75607-67-9

Additional Names: 2-F-ara-AMP

Manufacturers' Codes: NSC-328002; NSC-312887

Trademarks: Fludara (Schering AG)

Molecular Formula: C10H13FN5O7P

Molecular Weight: 365.21

Percent Composition: C 32.89%, H 3.59%, F 5.20%, N 19.18%, O 30.67%, P 8.48%

Properties: Sol in water.

 

Therap-Cat: Phosphate as antineoplastic.

Keywords: Antineoplastic; Antimetabolites; Purine Analogs.

CAS Number75607-67-9
Product NameFludarabine phosphate
IUPAC Name[(2R,3S,4S,5R)-5-(6-amino-2-fluoropurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl dihydrogen phosphate
Molecular FormulaC10H13FN5O7P
Molecular Weight365.21 g/mol
InChIInChI=1S/C10H13FN5O7P/c11-10-14-7(12)4-8(15-10)16(2-13-4)9-6(18)5(17)3(23-9)1-22-24(19,20)21/h2-3,5-6,9,17-18H,1H2,(H2,12,14,15)(H2,19,20,21)/t3-,5-,6+,9-/m1/s1
InChI KeyGIUYCYHIANZCFB-FJFJXFQQSA-N
SMILESC1=NC2=C(N=C(N=C2N1C3C(C(C(O3)COP(=O)(O)O)O)O)F)N
Solubility2.97e+00 g/L
Water 9.2 (mg/mL)
pH 4 buffer 27.6 (mg/mL)
pH 9 buffer 57 (mg/mL)
Synonyms9 beta-D-arabinofuranosyl-2-fluoroadenine monophosphate, 9H-purin-6-amine, 2-fluoro-9-(5-O-phosphono-beta-D-arabinofuranosyl)-, Beneflur, F-ara-AMP, FaraAMP, Fludara, fludarabine 5'-monophosphate, fludarabine monophosphate, fludarabine phosphate, fluoro-ara-AMP, NSC 312887, NSC-312887
Canonical SMILESC1=NC2=C(N=C(N=C2N1C3C(C(C(O3)COP(=O)(O)O)O)O)F)N
Isomeric SMILESC1=NC2=C(N=C(N=C2N1[C@H]3[C@H]([C@@H]([C@H](O3)COP(=O)(O)O)O)O)F)N
CAS No: 75607-67-9 Synonyms: 9-b-D-Arabinofuranosyl-2-fluoroadenine 5-phosphate2-Fluoroadenine arabinoside 5-monophosphateFludarabine 5-monophosphate[(2R,3R,4S,5R)-5-(6-Amino-2-fluoro-purin-9-yl)-3,4-dihydroxy-oxolan-2-yl]methoxyphosphonic acid MDL No: MFCD00866418 Chemical Formula: C10H13FN5O7P Molecular Weight: 365.21


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