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

• ChemBase编号: 944
• 分子式: C10H13FN5O7P
• 平均质量: 365.2116842
• 单一同位素质量: 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

名称和登记号

名称

• IUPAC标准名: {[(2R,3S,4S,5R)-5-(6-amino-2-fluoro-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy}phosphonic acid
• IUPAC传统名: fludarabine
• 商标名: Fludara; Fludura
• 别名: FAMP; Fludarabine 5'-monophosphate; Fludarabine monophosphate; Fludarabine phosphate; Fludarabine; Fludara; Fludarabine Phosphate(Fludara)

登记号

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

理论计算性质

JChem

• Acid pKa: 1.3406203
• 质子受体: 10
• 质子供体: 5
• LogD (pH = 5.5): -4.035218
• LogD (pH = 7.4): -5.1241035
• Log P: -1.9500656
• 摩尔折射率: 74.9321 cm^3
• 极化性: 28.966225 Å^3
• 极化表面积: 186.07 Å^2
• 可自由旋转的化学键: 4
• 里宾斯基五规则: true

ALOGPS 2.1

• Log P: -2.51
• LOG S: -2.09
• 溶解度: 2.97e+00 g/l

分子性质

理化性质

• 溶解度: 3.53 mg/ml; DMSO
• 疏水性(logP): -2.8

安全信息

• 保存条件: -20°C

药理学性质

• 作用靶点: Antimetabolites

产品相关信息

• 纯度: 97%
• 成盐信息: Phosphate

详细说明

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]

参考文献

• 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)