Nelarabine

Bezeichnung:Nelarabine

CAS-Nr121032-29-9

Englisch Name:Nelarabine

CBNumberCB01011878

SummenformelC11H15N5O5

Molgewicht297.27

MOL-Datei121032-29-9.mol

Nelarabine physikalisch-chemischer Eigenschaften

Schmelzpunkt	209-217°
alpha	D20 +55.9° (c = 0.27 in DMF)
Siedepunkt	721.0±70.0 °C(Predicted)
Dichte	1.98±0.1 g/cm3(Predicted)
storage temp.	2-8°C(protect from light)
Löslichkeit	DMSO (Slightly), Methanol (Slightly, Heated), Water (Slightly, Sonicated)
Aggregatzustand	Solid
pka	13.07±0.70(Predicted)
Farbe	White
InChI	InChI=1/C11H15N5O5/c1-20-9-5-8(14-11(12)15-9)16(3-13-5)10-7(19)6(18)4(2-17)21-10/h3-4,6-7,10,17-19H,2H2,1H3,(H2,12,14,15)/t4-,6-,7+,10-/s3
InChIKey	IXOXBSCIXZEQEQ-GCTRTDOSNA-N
SMILES	N1(C=NC2C(OC)=NC(N)=NC1=2)[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 \|&1:12,13,15,17,r\|
CAS Datenbank	121032-29-9(CAS DataBase Reference)

Gefahreninformationscode (GHS)

Nelarabine Chemische Eigenschaften,Einsatz,Produktion Methoden

Beschreibung
Nelarabine is a new member of the purine nucleoside antimetabolite class of drugs. It was launched as an intravenous infusion for treating relapsed or refractory T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL) after at least two prior chemotherapy regimens. Nelarabine is a pro-drug of 9-b-D-arabinofuranosylguanine (ara-G), a deoxyguanosine derivative with a high level of T-cell selective cytotoxicity. Although Ara-G has been known since the 1960s, it has not been used in clinical studies due to its poor solubility. Nelarabine is the O-methyl derivative of ara-G with approximately 10 times greater aqueous solubility. It is demethylated in vivo by adenosine deaminase to produce ara-G, which is subsequently converted to the active 5’-triphosphate, ara-GTP. Accumulation of ara-GTP in leukemic blasts allows for incorporation into DNA, leading to inhibition of DNA synthesis and cell death.
Originator
Glaxo Wellcome (US)
Verwenden
A chemotherapy drug used in the treatment of relapsed/refractory T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL).
Definition
ChEBI: Nelarabine is a purine nucleoside in which O-methylguanine is attached to arabinofuranose via a beta-N(9)-glycosidic bond. Inhibits DNA synthesis and causes cell death; a prodrug of 9-beta-D-arabinofuranosylguanine (ara-G). It has a role as an antineoplastic agent, a DNA synthesis inhibitor and a prodrug. It is a purine nucleoside, a beta-D-arabinoside and a monosaccharide derivative. It is functionally related to a guanine and a 9-beta-D-arabinofuranosylguanine.
Trademarks
Arranon (SmithKline Beecham).
Clinical Use
Antineoplastic agent:
T-cell acute lymphoblastic leukaemia (T-ALL)
T-cell lymphoblastic lymphoma (T-LBL)
Synthese
The drug was synthesized by enzymatic coupling of arabinosyluracil 87, prepared according to literature and 2-amino- 6-methoxy purine 88 using purine nucleoside phosphorylase (PNP) and uridine phosphorylase (UP) in phosphate buffer for 30 days to give the nelarabine (XIII) in 48% yield.
Stoffwechsel
Nelarabine is a pro-drug of the deoxyguanosine analogue ara-G. Extensive metabolism by O-demethylation by adenosine deaminase to form ara-G, which undergoes hydrolysis to form guanine. In addition, some nelarabine is hydrolysed to form methylguanine, which is O-demethylated to form guanine. Guanine is N-deaminated to form xanthine, which is further oxidised to yield uric acid. Nelarabine and ara-G are partially eliminated by the kidneys.
Lager
Store at +4°C
Einzelnachweise
[1] cohen mh, johnson jr, massie t, et al. approval summary: nelarabine for the treatment of t-cell lymphoblastic leukemia/lymphoma. clin cancer res. september 2006. 18:5329–35.
[2] yesid alvarado, mary alma welch, ronan swords, john bruzzi, ellen schlette, francis j. giles. nelarabine activity in acute biphenotypic leukemia. leukemia research. november 2007. 31(11): 1600-1603.

Nelarabine Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

121032-29-9, Nelarabine Verwandte Suche:

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