{[(2R,3S,4S,5R)-5-(6-amino-2-fluoro-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy}phosphonic acid

• ChemBase ID: 944
• Molecular Formular: C10H13FN5O7P
• Molecular Mass: 365.2116842
• Monoisotopic Mass: 365.05366263
• SMILES: P(=O)(OC[C@H]1O[C@@H](n2c3nc(F)nc(N)c3nc2)[C@@H](O)[C@@H]1O)(O)O
• Canonical SMILES: O[C@H]1[C@H](O)[C@H](O[C@H]1n1cnc2c1nc(F)nc2N)COP(=O)(O)O
• InChI: InChI=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
• InChIKey: GIUYCYHIANZCFB-FJFJXFQQSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: {[(2R,3S,4S,5R)-5-(6-amino-2-fluoro-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy}phosphonic acid
• IUPAC Traditional name: fludarabine
• Brand Name: Fludara; Fludura
• Synonyms: FAMP; Fludarabine 5'-monophosphate; Fludarabine monophosphate; Fludarabine phosphate; Fludarabine; Fludara; Fludarabine Phosphate(Fludara)

Database IDs

• CAS Number: 1679-14-1; 75607-67-9
• PubChem SID: 160964407; 46507525
• PubChem CID: 30751

CALCULATED PROPERTIES

JChem

• Acid pKa: 1.3406203
• H Acceptors: 10
• H Donor: 5
• LogD (pH = 5.5): -4.035218
• LogD (pH = 7.4): -5.1241035
• Log P: -1.9500656
• Molar Refractivity: 74.9321 cm^3
• Polarizability: 28.966225 Å^3
• Polar Surface Area: 186.07 Å^2
• Rotatable Bonds: 4
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: -2.51
• LOG S: -2.09
• Solubility (Water): 2.97e+00 g/l

PROPERTIES

Physical Property

• Solubility: 3.53 mg/ml; DMSO
• Hydrophobicity(logP): -2.8

Safety Information

• Storage Condition: -20°C

Pharmacology Properties

• Target: Antimetabolites

Product Information

• Purity: 97%
• Salt Data: Phosphate

DETAILS

DrugBank - DB01073

• Drug Groups: approved
• Description: Fludarabine (marketed as fludarabine phosphate under the trade name Fludara) is a chemotherapy drug used in the treatment of hematological malignancies. [Wikipedia]
• Indication: 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 regimen
• Pharmacology: Fludarabine is a chemotherapy drug used in the treatment of chronic lymphocytic leukemia. It acts at DNA polymerase alpha, ribonucleotide reductase and DNA primase, results in the inhibition of DNA synthesis, and destroys the cancer cells.
• Affected Organisms: Humans and other mammals
• Absorption: Bioavailability is 55% following oral administration.
• Half Life: 20 hours
• Protein Binding: 19-29%
• Clearance: * 117-145 mL/min [patients with B-cell CLL receiving IV administration of a single dose of 40 mg/m2]
• References: Rai KR, Peterson BL, Appelbaum FR, Kolitz J, Elias L, Shepherd L, Hines J, Threatte GA, Larson RA, Cheson BD, Schiffer CA: Fludarabine compared with chlorambucil as primary therapy for chronic lymphocytic leukemia. N Engl J Med. 2000 Dec 14;343(24):1750-7. [Pubmed] ; Gonzalez H, Leblond V, Azar N, Sutton L, Gabarre J, Binet JL, Vernant JP, Dighiero G: Severe autoimmune hemolytic anemia in eight patients treated with fludarabine. Hematol Cell Ther. 1998 Jun;40(3):113-8. [Pubmed] ; Tournilhac O, Cazin B, Lepretre S, Divine M, Maloum K, Delmer A, Grosbois B, Feugier P, Maloisel F, Villard F, Villemagne B, Bastit D, Belhadj K, Azar N, Michallet M, Manhes G, Travade P: Impact of frontline fludarabine and cyclophosphamide combined treatment on peripheral blood stem cell mobilization in B-cell chronic lymphocytic leukemia. Blood. 2004 Jan 1;103(1):363-5. Epub 2003 Sep 11. [Pubmed]
• External Links: Wikipedia; RxList; Drugs.com

Selleck Chemicals - S1229

Research Area: Cancer
Biological Activity:
Fludarabine Phosphate (Fludara) is a nucleoside analogue and formulated as the monophosphate form of F-ara-AMP(fludarabine, IC50 < 3 μM). To enhance solubility, Fludara is formulated as the monophosphate (F-ara-AMP, fudarabine), which is instantaneously and quantitatively dephosphorylated to the parent nucleoside upon intravenous infusion. Inside the cells rephosphorylation occurs which leads to fuoroadenine arabinoside triphosphate (F-ara-ATP),the major cytotoxic metabolite of F-ara-A. This metabolite inhibits several key processes necessary for the DNA replication, i.e. enzymes required in the DNA synthesis, such as ribonucleotide reductase, DNA primase, DNA polymerase, 3’-5’ exonuclease activity of DNA polymerase d and e and DNA ligase I. [1] Fludarabine can also induce pro-inflammatory stimulation of monocytic cells, as evaluated by increased expression of ICAM-1 and IL-8 release. [2] Fludarabine did not affect the growth of ovarian cancer cell lines, whereas it induced a marked and dose-dependent inhibition of proliferation in melanoma cell lines. [3]

REFERENCES

• Rai KR, Peterson BL, Appelbaum FR, Kolitz J, Elias L, Shepherd L, Hines J, Threatte GA, Larson RA, Cheson BD, Schiffer CA: Fludarabine compared with chlorambucil as primary therapy for chronic lymphocytic leukemia. N Engl J Med. 2000 Dec 14;343(24):1750-7. Pubmed
• Gonzalez H, Leblond V, Azar N, Sutton L, Gabarre J, Binet JL, Vernant JP, Dighiero G: Severe autoimmune hemolytic anemia in eight patients treated with fludarabine. Hematol Cell Ther. 1998 Jun;40(3):113-8. Pubmed
• Tournilhac O, Cazin B, Lepretre S, Divine M, Maloum K, Delmer A, Grosbois B, Feugier P, Maloisel F, Villard F, Villemagne B, Bastit D, Belhadj K, Azar N, Michallet M, Manhes G, Travade P: Impact of frontline fludarabine and cyclophosphamide combined treatment on peripheral blood stem cell mobilization in B-cell chronic lymphocytic leukemia. Blood. 2004 Jan 1;103(1):363-5. Epub 2003 Sep 11. Pubmed
• Zaffaroni N et al. Eur J Cancer. 1996;32A(10)