75607-67-9 Usage
Description
Fludarabine phosphate is an antimetabolite indicated for the treatment of B cell
lymphocytic leukemia. It is reportedly effective in patients refractory to other
therapies. Fludarabine phosphate acts by inhibiting primer RNA synthesis. Its side
effects include bone marrow suppression, anemia, thrombocytopenia and neutropenia.
Originator
Southern Research Institute (U.S.A.)
Uses
Different sources of media describe the Uses of 75607-67-9 differently. You can refer to the following data:
1. anticonvulsant
2. Fludarabine phosphate is used for the treatment of chronic lymphatic leukemia and low-grade lymphoma. In the circulation,fludarabine phosphate is immediately dephosphorylated to the nucleoside fludarabine. About 30-40% of nucleoside fludarabine is excreted into the urine. In addition, fludarabine is metabolized into a hypoxanthine metabolite also excreted in the urine.Intracellularly,fludarabine is stepwise rephosphorylated to the active triphosphate. Deoxycytidine kinase is the dominant, if not the exclusive,enzyme for the formation of the monophosphate. Adenylate kinase and nucleoside diphosphate kinase are believed to be involved in the formation of the diphosphate and triphosphate,respectively.
Definition
ChEBI: Fludarabine phosphate is a purine arabinonucleoside monophosphate having 2-fluoroadenine as the nucleobase. A prodrug, it is rapidly dephosphorylated to 2-fluoro-ara-A and then phosphorylated intracellularly by deoxycytidine kinase to the active triphosphate, 2-fluoro-ara-ATP. Once incorporated into DNA, 2-fluoro-ara-ATP functions as a DNA chain terminator. It is used for the treatment of adult patients with B-cell chronic lymphocytic leukemia (CLL) who have not responded to, or whose disease has progressed during, treatment with at least one standard alkylating-agent containing regimenas. It has a role as an antimetabolite, an antineoplastic agent, an immunosuppressive agent, an antiviral agent, a prodrug and a DNA synthesis inhibitor. It is an organofluorine compound, a nucleoside analogue and a purine arabinonucleoside monophosphate. It derives from a 2-fluoroadenine.
Brand name
Fludara (Berlex).
Pharmacology
Fludarabine phosphate is rapidly dephosphorylated to 2-fluoro-ara-A and then phosphorylated intracellularly by deoxycytidine kinase to the active triphosphate, 2-fluoro-ara-ATP. This metabolite appears to act by inhibiting DNA polymerase alpha, ribonucleotide reductase and DNA primase, thus inhibiting DNA synthesis. The mechanism of action of this antimetabolite is not completely characterized and may be multi-faceted.
Phase I studies in humans have demonstrated that fludarabine phosphate is rapidly converted to the active metabolite, 2-fluoro-ara-A, within minutes after intravenous infusion.
Consequently, clinical pharmacology studies have focused on 2-fluoro-ara-A pharmacokinetics. After the five daily doses of 25 mg 2-fluoro-ara-AMP/m2 to cancer patients infused over 30 minutes, 2-fluoro-ara-A concentrations show a moderate accumulation. During a 5-day treatment schedule, 2-fluoro-ara-A plasma trough levels increased by a factor of about 2. The terminal half-life of 2-fluoro-ara-A was estimated as approximately 20 hours. In vitro, plasma protein binding of fludarabine ranged between 19% and 29%.
Clinical Use
Fludarabine phosphate (Fludara ? ), is a fluorinated nucleotide analog of the antiviral agent vidarabine, 9-β-D-arabinofuranosyladenine(ara-A), which differs only by the presence of a fluorine atom at position 2 of the purine moiety and a phosphate group at position 5 of the arabinose moiety (Plunkett et al., 1993). These structural modifications result in increased aqueous solubility and resistance to enzymatic degradation by adenosine deaminases compared to vidarabine (Brockman et al., 1977; Plunkett et al., 1990). Fludarabine phosphate is indicated for the treatment of patients with B-cell chronic lymphocytic leukemia (CLL) who have not responded to or whose disease has progressed during treatment with at least one standard alkylating agent containing regimen (Boogaerts et al., 2001; Rossi et al., 2004).
Drug interactions
Potentially hazardous interactions with other drugs
Antipsychotics: avoid concomitant use with
clozapine, increased risk of agranulocytosis.
Cytotoxics: increased pulmonary toxicity with
pentostatin (unacceptably high incidence of
fatalities); increases intracellular concentration of
cytarabine.
Metabolism
Intravenous fludarabine phosphate is rapidly
dephosphorylated to fludarabine which is taken up
by lymphocytes and rephosphorylated via the enzyme
deoxycytidine kinase to the active triphosphate
nucleotide. Clearance of fludarabine from the plasma
is triphasic; elimination is mostly via renal excretion:
40-60% of an intravenous dose is excreted in the urine.
The pharmacokinetics of fludarabine show considerable
inter-individual variation
Check Digit Verification of cas no
The CAS Registry Mumber 75607-67-9 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 7,5,6,0 and 7 respectively; the second part has 2 digits, 6 and 7 respectively.
Calculate Digit Verification of CAS Registry Number 75607-67:
(7*7)+(6*5)+(5*6)+(4*0)+(3*7)+(2*6)+(1*7)=149
149 % 10 = 9
So 75607-67-9 is a valid CAS Registry Number.
InChI:InChI=1/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
75607-67-9Relevant articles and documents
Synthesis method of fludarabine phosphate
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Paragraph 0041-0043; 0061-0065, (2020/08/22)
The invention provides a synthesis method of fludarabine phosphate, and the synthesis route is as follows: with vidarabine as a starting raw material, fludarabine is obtained through upper protection,nitrification, fluorination denitration and deprotection, so that the fludarabine is prepared by adopting a brand-new synthesis route; meanwhile, by improving the process of phosphorylation and refining of fludarabine, the reaction time is shortened, the generation of by-products is reduced, and the product quality is improved. The method has the following advantages: 1, the initial raw materialis beta-configuration, isomer separation is avoided, and the yield is improved; raw materials are easy to obtain, the route is simple, and the price is low; 3, salification and column-passing purification and separation are avoided, so that the method is suitable for industrialization.
Fludarabine phosphate preparation method
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Paragraph 0009, (2017/01/26)
The invention discloses a fludarabine phosphate preparation method. The method comprises the specific steps that fludarabine and triethyl phosphate are added into a reaction container, the reaction container is placed into a subzero 6 DEG C low-temperature reaction bath, phosphorus oxychloride is added on the stirring condition, water and dichloromethane are added into the reaction container after the reaction is performed for 12 h, standing is performed, then, extraction is performed to obtain a water phase and an organic phase, the pH value of the water phase is adjusted to 2-3, recrystallization is performed to obtain white focculus, and filtering and vacuum drying are performed to obtain a target product of fludarabine phosphate with the purity being 99.95%. The method has the advantages that reaction conditions are mild, operation is easy, the product is easy to separate and purify, the yield is high, the product is environmentally friendly, high in purity, small in organic solvent residual quantity and capable of meeting the medicinal standard, and the method is suitable for industrial production.
PROCESS FOR THE PREPARATION OF FLUDARABINE PHOSPHATE
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Page/Page column 4-5, (2008/06/13)
A description is given of a process for the preparation of 9-beta-D-arabinofuranosyl-2-fluoroadenine-5'-phosphate starting from 9-beta-D-arabinofuranosyl-2-fluoroadenine by reaction with a mixture composed of triethyl phosphate and phosphorus oxychloride and in accordance with a work-up which provides for the use of toluene.
