2-(β-D-Ribofuranosyl)-4-amino-1,3,5-triazin-2-on

AZACITIDINE · AZACYTIDINE · Vidaza · 5-AZAC · mylosar · 4-amino-1-β-D-ribofuranosyl-s-triazin-2(1H)-one · 5-AC · 5 AZC

Identifikatoren & physikalische Daten

CAS No.	320-67-2
Summenformel	C8H12N4O5
Durchschnittliche Molmasse	244,2 g/mol
Monoisotopische Masse	244,0807695 g/mol
SMILES	Nc1ncn([C@@H]2O[C@H](CO)[C@@H](O)[C@H]2O)c(=O)n1
InChIKey	NMUSYJAQQFHJEW-KVTDHHQDSA-N
PubChem CID	9444
ChEMBL	CHEMBL1489
ChEBI	CHEBI:2038
EC No.	206-280-2
DTXSID	DTXSID9020116
Lokaler Name	2-(β-D-Ribofuranosyl)-4-amino-1,3,5-triazin-2-on

Chemische & physikalische Eigenschaften

XLogP	-2,2
Polarare Oberfläche (TPSA)	141
H-Brücken-Donoren	4
H-Brücken-Akzeptoren	5
Frei drehbare Bindungen	2
Schwere Atome	17
Formalladung	0
Komplexität	384
Arzneimittel	Pharmaceuticals -> Listed in ZINC15Pharmaceuticals -> Antibiotics
LogP (Verteilungskoeffizient)	-3.5
Color/Form	Crystals from methanol
Löslichkeit	5 to 10 mg/mL at 70 °F (NTP, 1992)1.21e+01 g/LDMSO 52.7 (mg/mL)Distilled H2O 13.7-14.0 (mg/mL)0.1 N HCL 27.7-28.0 (mg/mL)Soluble in DMSO (up to 25 mg/ml), or in Water (up to 12 mg/ml).0.5-1.0 g/100 mL at 21 ºC
Human Drugs	Breast FeedingLactationMilk, HumanAntimetabolitesAntineoplastic AgentsEnzyme InhibitorsFDA approved drugs -> Active ingredientEMA approved medicines: Human medicine
Decomposition	When heated to decomposition it emits toxic fumes of /nitrogen oxides/.
Schmelzpunkt	442 to 446 °F (decomposes) (NTP, 1992)228-230 °C (decomposes)229 °C226-232 °C (dec.)(lit.)
Optical Rotation	Optical rotation: + 39 degrees @ 25 °C (c = 1 in water)(c = 1, H2O) [a]20 D = 40.0 ± 1.0°
Physical Description	5-azacytidine is a white crystalline powder. (NTP, 1992)Solid
Stability/Shelf Life	Intact vials should be stored under refrigeration & are stable for a least 4 yr. Although the drug is stable for 3 yr at room temp, refrigeration is recommended because degradation may result at elevated temperatures. The constituted soln hydrolyzes at room temp & should be used within 30 min. The pH providing optimum soln stability has been reported to be about 6.5-7. Azacitidine 0.5 & 2 mg/ml in Ringer's injection, lactated, was stable for up to one month when frozen at -20 °C in polypropylene syringes.Bulk: Samples of 5- azacitidine and 5- azacitidine hydrate were found to be stable at 25 °C and 60 °C for at least 30 days. Solution: Dilute aqueous solutions of 5-azacitidine have been found to be unstable at 24 -26 ° C. A 1% aqueous solution at 5-6°C decomposes 2, 5, and 9% in 2, 8, and 24 hours respectively. At room temperature a 1% aqueous solution shows 7, 20 and 41% decomposition in 2, 8, and 24 hours respectively (UV and NMR).
Collision Cross Section	150.12 Å² [M+H]+ [CCS Type: TWMethod: calibrated with polyalanine and drug standards]
Siedepunkt	387.12°C (rough estimate)
Dichte	1.4287 (rough estimate)
Brechungsindex	1.6590 (estimate)
Lagerbedingungen	-20°C
Aggregatzustand	lyophilized powder
pKa (Säurekonstante)	13.46±0.70(Predicted)
Farbe	White to Off-white
Biologische Quelle	synthetic (organic)
Merck	14,887
BRN	620461
Stabilität	Stable for 2 years from date of purchase as supplied. Solutions in DMSO or distilled water may be stored at -20° for up to 1 month.
InChI	1S/C8H12N4O5/c9-7-10-2-12(8(16)11-7)6-5(15)4(14)3(1-13)17-6/h2-6,13-15H,1H2,(H2,9,11,16)/t3-,4-,5-,6-/m1/s1
InChIKey	NMUSYJAQQFHJEW-WGDKFINWSA-N
SMILES	NC1=NC(=O)N(C=N1)[C@@H]2O[C@H](CO)[C@@H](O)[C@H]2O
LogP (Verteilungskoeffizient)	-2.191 (est)
CAS Datenbank	320-67-2(CAS DataBase Reference)
EPA chemische Informationen	Azacitidine (320-67-2)

Sicherheit & Vorschriften

GHS-Einstufung	DangerH302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]P203, P264, P270, P280, P301+P317, P318, P330, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 85 reports by companies from 10 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.H302: Harmful if swallowed [Warning Acute toxicity, oral]
Regulatorische Informationen	Hazard Traits - Carcinogenicity
Brandgefahren	Flash point data for this chemical are not availablehowever, it is probably combustible. (NTP, 1992)
Gesundheitsgefahren	SYMPTOMS: Symptoms of exposure to this compound via intravenous route include nausea, vomiting, diarrhea, reduction in white cell count, leukopenia and agranulocytosis. Other symptoms via intravenous route include dose-related leukemia, thrombocytopenia, myelosuppression, gastrointestinal upset, alterations in hepatic function tests, fatal hepatic coma, myalgia, rhabdomyolysis, rash, stomatitis, fever, hypotension and reversible renal impairment. Symptoms of exposure to this type of compound include anorexia, local irritant effects, allergic reactions including pruritus and erythema, headache, malaise, weakness, anaphylaxis, vesicant or irritant effect on skin and mucous membranes, thrombophlebitis, anemia, bleeding, immunosuppressant effect, mouth ulcers, esophagitis, abdominal pain, hemorrhage, perforation of the stomach, alopecia, delayed wound healing, amenorrhea, inhibition of spermatogenesis, gynecomastia, hyperuricemia, acute renal failure due to uric acid nephropathy, hyperphosphatemia, disturbances of electrolyte balance, pigmentation of the skin and nails, jaundice and abnormal liver function tests.
Reaktive Gruppe	Alcohols and Polyols
Special Reports	National Toxicology Program. Eleventh Report on Carcinogens (2005). The Report on Carcinogens is an informational scientific and public health document that identifies and discusses substances (including agents, mixtures, or exposure circumstances) that may pose a carcinogenic hazard to human health. Azacitidine (320-67-2) is listed as reasonably anticipated to be a human carcinogen.[Available from, as of July 31, 2009: http://ntp.niehs.nih.gov/ntp/roc/eleventh/profiles/s017azac.pdf]

Anwendungen & Verwendung

Beschreibung

5-Azacytidine is an analog of the nucleoside cytidine which can be incorporated into DNA and RNA. 5-Azacytidine acts as an epigenetic modifier by incorporating into DNA where it irreversibly binds to DNA methyltransferases, thus inhibiting their activity.Azacitidine is an antineoplastic agent launched for the treatment of myelodysplastic syndrome (MDS). MDS is a group of closely related diseases caused by abnormal blood-forming stem cells of the bone marrow. Azacitidine is indicated for the treatment of all five subtypes of MDS, which consist of refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, and chronic myelomonocytic leukemia.

Verwenden

5-Azacytidine, its incorporation into RNA alters RNA synthesis and processing, and results in inhibition of protein synthesis. It has been used as a cancer chemotherapeutic agent. It is a powerful bacteriostatic, antitumor, and mutagenic agent; it also exhibits immunosuppressive, antimitotic, radioprotective, and virostatic effects.