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147-94-4 molecular structure
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4-amino-1-[(2R,3S,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1,2-dihydropyrimidin-2-one

ChemBase ID: 861
Molecular Formular: C9H13N3O5
Molecular Mass: 243.21662
Monoisotopic Mass: 243.08552053
SMILES and InChIs

SMILES:
O1[C@@H](n2ccc(nc2=O)N)[C@@H](O)[C@H](O)[C@H]1CO
Canonical SMILES:
OC[C@H]1O[C@H]([C@H]([C@@H]1O)O)n1ccc(nc1=O)N
InChI:
InChI=1S/C9H13N3O5/c10-5-1-2-12(9(16)11-5)8-7(15)6(14)4(3-13)17-8/h1-2,4,6-8,13-15H,3H2,(H2,10,11,16)/t4-,6-,7+,8-/m1/s1
InChIKey:
UHDGCWIWMRVCDJ-CCXZUQQUSA-N

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CBID:861 http://www.chembase.cn/molecule-861.html

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NAMES AND DATABASE IDS

NAMES AND DATABASE IDS

Names Database IDs
IUPAC name
4-amino-1-[(2R,3S,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1,2-dihydropyrimidin-2-one
IUPAC Traditional name
cytarabine
Brand Name
AR3
Alexan
Arabitin
Arafcyt
Cytarbel
Cytosar
Cytosar-U
Depocyt
Depocyt (liposomal)
Erpalfa
Iretin
Spongocytidine
Tarabine
Udicil
Synonyms
(β-D-Arabinofuranosyl)cytosine
Cytarabine
Cytosine β-D-arabinofuranoside
Ara-C
Arabinocytidine
Arabinofuranosylcytosine
Arabinosylcytosine
AraC
Aracytidine
Aracytin
Aracytine
beta-Arabinosylcytosine
Beta-cytosine arabinoside
beta-D-Arabinosylcytosine
Citarabina [INN-Spanish]
Cytarabina
Cytarabin
Cytarabinoside
Cytarabinum [INN-Latin]
Cytosine 1-beta-D-arabinofuranoside
Cytosine beta-D-arabinoside
Cytosine arabinoside
Cytosine arabinose
Cytosine arabinofuranoside
Cytosine, beta-D-arabinoside
Cytosine-1-beta-D-arabinofuranoside
Cytosine-beta-arabinoside
Cytosine-beta-D-arabinofuranoside
cytarabine liposome injection
Cytarabine
Cytosar-U
4-AMino-1-((2R,3S,4S,5R)-3,4-dihydroxy-5-(hydroxyMethyl)tetrahydrofuran-2-yl)pyriMidin-2(1H)-one
(β-D-阿拉伯呋喃糖基)胞嘧啶
胞嘧啶阿拉伯糖苷
阿拉伯糖胞嘧啶
阿糖胞嘧啶
阿糖胞苷
胞嘧啶 β-D-呋喃阿拉伯糖苷
CAS Number
147-94-4
EC Number
205-705-9
MDL Number
MFCD00066487
Beilstein Number
89175
PubChem SID
46505879
24892435
160964324
24858315
PubChem CID
6253

CALCULATED PROPERTIES

CALCULATED PROPERTIES

JChem ALOGPS 2.1
Acid pKa 12.553241  H Acceptors
H Donor LogD (pH = 5.5) -2.7975185 
LogD (pH = 7.4) -2.7975204  Log P -2.7975173 
Molar Refractivity 54.5448 cm3 Polarizability 21.48729 Å3
Polar Surface Area 128.61 Å2 Rotatable Bonds
Lipinski's Rule of Five true 
Log P -2.18  LOG S -0.74 
Solubility (Water) 4.38e+01 g/l 

PROPERTIES

PROPERTIES

Physical Property Safety Information Pharmacology Properties Product Information Bioassay(PubChem)
Solubility
DMSO expand Show data source
Freely soluble expand Show data source
H2O: soluble50 mg/mL, clear, colorless expand Show data source
Apperance
crystalline expand Show data source
Optical Rotation
[α]20/D +158±2°, c = 1% in H2O expand Show data source
Hydrophobicity(logP)
-2.8 expand Show data source
Storage Condition
-20°C expand Show data source
RTECS
HA5425000 expand Show data source
European Hazard Symbols
Harmful Harmful (Xn) expand Show data source
MSDS Link
Download expand Show data source
German water hazard class
3 expand Show data source
Risk Statements
63-43 expand Show data source
Safety Statements
36/37 expand Show data source
GHS Pictograms
GHS07 expand Show data source
GHS08 expand Show data source
GHS Signal Word
Warning expand Show data source
GHS Hazard statements
H317-H361 expand Show data source
GHS Precautionary statements
P280 expand Show data source
Personal Protective Equipment
Eyeshields, Faceshields, full-face particle respirator type N100 (US), Gloves, respirator cartridge type N100 (US), type P1 (EN143) respirator filter, type P3 (EN 143) respirator cartridges expand Show data source
Storage Temperature
2-8°C expand Show data source
Gene Information
human ... POLB(5423)mouse ... Cda(72269) expand Show data source
Purity
≥90% (HPLC) expand Show data source
≥99.0% (HPLC) expand Show data source
98% expand Show data source
Salt Data
Free Base expand Show data source
Empirical Formula (Hill Notation)
C9H13N3O5 expand Show data source

DETAILS

DETAILS

DrugBank DrugBank Selleck Chemicals Selleck Chemicals Sigma Aldrich Sigma Aldrich
DrugBank - DB00987 external link
Item Information
Drug Groups approved; investigational
Description A pyrimidine nucleoside analog that is used mainly in the treatment of leukemia, especially acute non-lymphoblastic leukemia. Cytarabine is an antimetabolite antineoplastic agent that inhibits the synthesis of DNA. Its actions are specific for the S phase of the cell cycle. It also has antiviral and immunosuppressant properties. (From Martindale, The Extra Pharmacopoeia, 30th ed, p472)
Indication For the treatment of acute non-lymphocytic leukemia, acute lymphocytic leukemia and blast phase of chronic myelocytic leukemia.
Pharmacology Cytarabine is an antineoplastic anti-metabolite used in the treatment of several forms of leukemia including acute myelogenous leukemia and meningeal leukemia. Anti-metabolites masquerade as purine or pyrimidine - which become the building blocks of DNA. They prevent these substances becoming incorporated in to DNA during the "S" phase (of the cell cycle), stopping normal development and division. Cytarabine is metabolized intracellularly into its active triphosphate form (cytosine arabinoside triphosphate). This metabolite then damages DNA by multiple mechanisms, including the inhibition of alpha-DNA polymerase, inhibition of DNA repair through an effect on beta-DNA polymerase, and incorporation into DNA. The latter mechanism is probably the most important. Cytotoxicity is highly specific for the S phase of the cell cycle.
Toxicity Cytarabine syndrome may develop - it is characterized by fever, myalgia, bone pain, occasionally chest pain, maculopapular rash, conjunctivitis, and malaise.
Affected Organisms
Humans and other mammals
Biotransformation Hepatic.
Absorption Less than 20% of the orally administered dose is absorbed from the gastrointestinal tract.
Half Life 10 minutes
Protein Binding 13%
Elimination The primary route of elimination of cytarabine is metabolism to the inactive compound ara-U, followed by urinary excretion of ara-U.
External Links
Wikipedia
RxList
Drugs.com
Selleck Chemicals - S1648 external link
Research Area
Description Cancer
Biological Activity
Description Cytarabine (Cytosine arabinoside, AraC) is an antimetabolic agent and DNA synthesis inhibitor with IC50 of 16 nM in wild-type CCRF-CEM cells.
Targets DNA synthesis
IC50 16 nM [1] in wild-
In Vitro Cytarabine (AraC) is phosphorylated into a triphosphate form (Ara-CTP) involving deoxycytidine kinase (dCK), which competes with dCTP for incorporation into DNA, and then blocks DNA synthesis by inhibiting the function of DNA and RNA polymerases. Cytarabine displays a higher growth inhibitory activity towards wild-type CCRF-CEM cells compared to other acute myelogenous leukemia (AML) cells with IC50 of 16 nM. [1] Increasing concentrations of Cytarabine (IC50 of 0.69 μM) results in decreased metabolic activity of sensitive rat leukemic cell line RO/1, and the cell toxity can be highly enhanced by transfection with human wt dCK (IC50 of 0.037 μM) but not the inactive, alternatively spliced dCK forms. [2] Cytarabine apparently induces apoptosis of rat sympathetic neurons at 10 μM, of which 100 μM shows the highest toxicity and kills over 80% of the neurons by 84 hours, involving the release of mitochondrial cytochrome-c and the activation of caspase-3, and the toxicity can be attenuated by p53 knockdown and delayed by bax deletion. [3]
In Vivo Cytarabine is highly effective against acute leukaemias, which causes the characteristic G1/S blockage and synchronization, and increases the survival time for leukaemic Brown Norway rats in a weak dose-related fashion indicating that the use of higher dosages of Cytarabine does not contribute to its antileukaemic effectiveness in man. [4] Cytarabine (250 mg/kg) also causes placental growth retardation and increases placental trophoblastic cells apoptosis in the placental labyrinth zone of the pregnant Slc:Wistar rats, which increases from 3 hour after the treatment and peaks at 6 hour before returning to control levels at 48 hour, with remarkably enhanced p53 protein, p53 trancriptional target genes such as p21, cyclinG1 and fas and caspase-3 activity. [5]
Clinical Trials Phase I-II has been completed in the study of Oxaliplatin, Fludarabine, Cytarabine and Rituximab in patients with Richter's transformation, prolymphocytic leukemia or refractory/relapsed B-cell chronic lymphocytic leukemia.
Features Cytarabine is the first of a series of cancer drugs that altered the sugar component of nucleosides.
Protocol
Kinase Assay [1]
In Vitro Growth Inhibition Assay Stock solution of Cytarabine is prepared in absolute ethanol, and serial dilutions of Cytarabine are prepared. CCRF-CEM cells are suspended in RPMI medium supplemented with 10% FBS, 0.1% gentamicin, and 1% sodium pyruvate. The cells are suspended in their respective media to give 10 mL volumes of cell suspension at a final density of 3-6 × 104 cells/mL. Appropriate volumes of Cytarabine solution are transferred to the cell suspensions, and incubation is continued for 72 hours. The cells are spun down and resuspended in fresh Cytarabine -free medium, and final cell counts are determined. The data are analyzed by sigmoidal curve fitting of the cell count versus Cytarabine concentration, and the results are expressed as the IC50 (Cytarabine concentration that inhibits cell growth to 50% of the control value).
Cell Assay [2]
Cell Lines Rat leukemic cell lines RCL/0, RO/1 and K7 and human myelomonocytic leukemic U937
Concentrations ~100 μM
Incubation Time 24, 48 and 72 hours
Methods Cells are incubated in the presence of different concentrations of Cytarabine at 37 °C for 24, 48, and 72 hours. At the time of 20-, 44-, or 68-hour incubation in the presence of Cytarabine, 10 mL of cell proliferation reagent WST-1 solution is added. After 2- and 4-hour incubation with WST-1, cell metabolic activity is assessed with colorimetric changes quantified by measuring the absorbance in a spectrophotometer at 450 nm. And cell division times are calculated from eosin counting in parallel with viability assays.
Animal Study [4]
Animal Models Brown Norway rat with myelocytic leukaemia
Formulation Dissolved in phosphate-buffered saline (pH 7.0) just before use.
Doses 5 - 1000 mg/kg
Administration Injection i.v.
References
[1] Tobias SC, et al. Mol Pharm, 2004, 1(2), 112-116.
[2] Veuger MJ, et al. Blood, 2002, 99(4), 1373-1380.
[3] Besirli CG, et al. Cell Death Differ, 2003, 10(9), 1045-1058.
[4] Richel DJ, Br J Cancer, 1988, 58(6), 730-733.
[5] Yamauchi H, et al. Biol Reprod, 2004, 70(6), 1762-1767.
Sigma Aldrich - C1768 external link
Biochem/physiol Actions
阿糖胞苷复合到 DNA 中后,可通过与导致 DNA 断裂的拓扑异构酶 I 形成可裂解复合物而抑制 DNA 的复制,但不会抑制 RNA 的合成。抗白血病制剂。
Sigma Aldrich - 30399 external link
Biochem/physiol Actions
Ara-C incorporates into DNA and inhibits DNA replication by forming cleavage complexes with topoisomerase I resulting in DNA fragmentation; does not inhibit RNA synthesis. Anti-leukemia agent.

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