6-Mercaptopurine monohydrate

Bezeichnung:6-Mercaptopurine monohydrate

CAS-Nr6112-76-1

Englisch Name:6-Mercaptopurine monohydrate

CBNumberCB7337963

SummenformelC5H6N4OS

Molgewicht170.19

MOL-Datei6112-76-1.mol

6-Mercaptopurine monohydrate physikalisch-chemischer Eigenschaften

Schmelzpunkt	>300 °C(lit.)
storage temp.	2-8°C
Löslichkeit	INSOLUBLE
Aggregatzustand	Fine Powder
Farbe	Yellow
Wasserlöslichkeit	INSOLUBLE
Merck	14,5871
BRN	4012091
BCS Class	4
Stabilität	Stable. Incompatible with strong oxidizing agents, acids, strong bases. Light sensitive.
CAS Datenbank	6112-76-1(CAS DataBase Reference)
EPA chemische Informationen	Mercaptopurine monohydrate (6112-76-1)

Sicherheit

Kennzeichnung gefährlicher	Xn,Xi
R-Sätze:	22-36/37/38-63-20/21/22
S-Sätze:	22-36/37/39-45-36/37
RIDADR	UN 2811 6.1 / PGIII
WGK Germany	3
RTECS-Nr.	UP0400000
HS Code	29335995

Gefahreninformationscode (GHS)

6-Mercaptopurine monohydrate Chemische Eigenschaften,Einsatz,Produktion Methoden

R-Sätze Betriebsanweisung:
R22:Gesundheitsschädlich beim Verschlucken.
R36/37/38:Reizt die Augen, die Atmungsorgane und die Haut.
R63:Kann das Kind im Mutterleib möglicherweise schädigen.
R20/21/22:Gesundheitsschädlich beim Einatmen,Verschlucken und Berührung mit der Haut.
S-Sätze Betriebsanweisung:
S22:Staub nicht einatmen.
S36/37/39:Bei der Arbeit geeignete Schutzkleidung,Schutzhandschuhe und Schutzbrille/Gesichtsschutz tragen.
S45:Bei Unfall oder Unwohlsein sofort Arzt zuziehen (wenn möglich, dieses Etikett vorzeigen).
S36/37:Bei der Arbeit geeignete Schutzhandschuhe und Schutzkleidung tragen.
Beschreibung
6-Mercaptopurine (6-MP) is an inhibitor of purine synthesis and interconversion. It is rapidly converted to 6-mercaptopurine ribonucleoside-5''-monophosphate, which inhibits phosphoribosyl pyrophosphate (PRPP) amidotransferase, the rate-limiting enzyme in purine synthesis. It also inhibits the conversion of IMP to adenylosuccinic acid and xanthylic acid and blocks AMP formation in vitro. 6-MP (30 mg/kg) inhibits growth of sarcoma 180, adenocarcinoma E 0771, and adenocarcinoma 755 tumors and reduces the size of leukemia L1210 subcutaneous growths in mice. It also decreases delayed-type hypersensitivity and thyroid inflammation in a guinea pig model of thyroiditis when administered pre- or post-disease onset. Formulations containing mercaptopurine have been used for maintenance therapy in patients with acute lymphoblastic leukemia.
Chemische Eigenschaften
white to light yellow crystal powder
Verwenden
An immunosuppressive drug used to treat leukemia. It is also used for pediatric non-Hodgkin lymphoma, polycythemia vera, and psoriatic arthritis
Verwenden
antihypertensive, ACE inhibitor
Verwenden
An immunosuppressive drug used to treat leukemia. It is also used for pediatric non-Hodgkin’s lymphoma, polycythemia vera, and psoriatic arthritis.
Indications
Mercaptopurine (Purinethol) is an analogue of hypoxanthine and was one of the first agents shown to be active against acute leukemias. It is now used as part of maintenance therapy in acute lymphoblastic leukemia. Mercaptopurine must be activated to a nucleotide by the enzyme HGPRTase. This metabolite is capable of inhibiting the synthesis of the normal purines adenine and guanine at the initial aminotransferase step and inhibiting the conversion of inosinic acid to the nucleotides adenylate and guanylate at several steps. Some mercaptopurine is also incorporated into DNA in the form of thioguanine. The relative significance of these mechanisms to the antitumor action of mercaptopurine is not clear.
Resistance to mercaptopurine may be a result of decreased drug activation by HGPRTase or increased inactivation by alkaline phosphatase.
The plasma half-life of an intravenous bolus injection of mercaptopurine is 21 minutes in children and 47 minutes in adults. After oral administration, peak plasma levels are attained within 2 hours. The drug is 20% bound to plasma proteins and does not enter the CSF. Xanthine oxidase is the primary enzyme involved in the metabolic inactivation of mercaptopurine.
Mercaptopurine is used in the maintenance therapy of acute lymphoblastic leukemia. It also displays activity against acute and chronic myelogenous leukemias.
The major toxicities of mercaptopurine are myelosuppression, nausea, vomiting, and hepatic toxicity.
Definition
ChEBI: Mercaptopurine hydrate is a hydrate. It contains a mercaptopurine.
Trademarks
Purinethol (Teva).
Allgemeine Beschreibung
The drug is available as a 50-mg tablet for oral use. The primaryuses of mercaptopurine are in the treatment of lymphoblasticleukemia, acute lymphocytic leukemia, and Crohndisease. The mechanism of action includes incorporation ofmercaptopurine into DNA and RNA via the triphosphatemetabolite. This incorporation inhibits synthesis and functionof the resulting modified DNA or RNA. The parent drug isinactive and requires phosphorylation for activity. Resistancecan occur via decreased expression of the activating enzymesor increased expression of the major catabolic enzymes.Oral absorption is generally incomplete (about 50%) andthe drug does not enter the CNS in therapeutic quantities.Mercaptopurine is metabolized by methylation, and themethylated product has anticancer activity. Oxidation byxanthine oxidase yields inactive metabolites. The concurrentuse of xanthine oxidase inhibitors such as allopurinol can enhancethe potency of mercaptopurine by inhibiting its catabolicbreakdown. The toxicities for mercaptopurine includemyelosuppression, immunosuppression, nausea, vomiting,diarrhea, dry skin, urticaria, and photosensitivity.
Allgemeine Beschreibung
Odorless light yellow to yellow crystalline powder. Becomes anhydrous at 284°F.
Air & Water Reaktionen
6-Mercaptopurine monohydrate is sensitive to light and oxidation. Insoluble in water.
Reaktivität anzeigen
6-Mercaptopurine monohydrate reacts with strong oxidizing agents, strong bases and strong acids.
Brandgefahr
Flash point data for 6-Mercaptopurine monohydrate are not available. 6-Mercaptopurine monohydrate is probably combustible.
Mechanism of action
Because the major mechanism of action of mercaptopurine is inhibition of de novo purine nucleotide biosynthesis rather than apoptosis secondary to the incorporation of false nucleotides into DNA, there is a lower risk for mutagenesis and secondary malignancy compared to thioguanine.
Clinical Use
Mercaptopurine is used in the treatment of acute lymphatic and myelogenous leukemias.
Nebenwirkungen
Bone marrow suppression is the major use-limiting toxicity, although the drug can be hepatotoxic in high doses. Dosage adjustments should be considered in the face of renal or hepatic impairment.
Synthese
Mercaptopurine, 6-purinthiol, is made from uric acid (30.1.2.5), which is synthesized from barbituric acid (30.1.2.1). Barbituric acid (30.1.2.1) is easily made by condensing urea with malonic ester and then nitrosylating it with nitrous acid. The nitrosoderivative (30.1.2.2) is reduced by hydrogen (obtained in situ by reacting tin with hydrochloric acid) to an amine (uramil) (30.1.2.3), and then reacted with isocyanic acid, which forms pseudouric acid (30.1.2.4). This undergoes cyclization to uric acid (30.1.2.5) when heated in the presence of hydrochloric acid. Upon reacting phosphorous pentachloride with uric acid, 2,6,8-trichloropurine (30.1.2.6) is formed. The three chlorine atoms in trichloropurine differ significantly in terms of reactivity for nucleophilic substitution. The chlorine atom at C6 is much more active than the chlorine atom at C2, and this is more active than the chlorine atom at C8, which allows subsequent manipulation by them. Interaction of 2,6,8-trichloropurine (30.1.2.6) with sodium hydroxide allows to replace the chlorine atom at C6, forming the dichloro-derivative (30.1.2.7), which is then reduced by hydriodic acid to hypoxanthine (30.1.2.8). Upon reaction with phosphorous pentasulfide, hypoxanthine is transformed into mercaptopurine (30.1.2.9).
Arzneimittelwechselwirkung
Potentially hazardous interactions with other drugs
Allopurinol: decreased rate of metabolism of mercaptopurine - reduce dose of mercaptopurine to a quarter of normal dose.
Antibacterials: increased risk of haematological toxicity with co-trimoxazole and trimethoprim.
Anticoagulants: possibly reduced anticoagulant effect of coumarins.
Antipsychotics: avoid with clozapine (increased risk of agranulocytosis).
Febuxostat: avoid concomitant use.
Stoffwechsel
It is available in an oral dosage form, but absorption can be erratic and is reduced by the presence of food. The drug is extensively metabolized on first pass and excreted by the kidneys.
läuterung methode
Crystallise 6-mercaptopurine from pyridine (30mL/g), wash it with pyridine, then triturate with water (25mL/g) and adjust to pH 5 by adding M HCl. Recrystallise it by heating, then cooling, the solution. Filter off the solid, wash it with water and dry it at 110o. It has also been crystallised from water (charcoal) as yellow crystals of the monohydrate which become anhydrous on drying at 140o. It has UV: at 230 and 312nm ( 14,000 and 19,600) in 0.1N NaOH; 222 and 327nm ( 9,2400 max and 21,300), and 216 and 329nm ( 8,740 and 19,300) in MeOH. It forms a 1:1 complex with Zn2+ , Pb2+ , Co2+, and Ni2+ in aqueous dioxan. It is an antineoplastic. [Albert & Brown J Chem Soc 2060 1954, IR: Brown & Mason J Chem Soc 682 1957, UV: Fox et al. J Am Chem Soc 80 1669 1958, UV: Mason J Chem Soc 2071 1954, Beilstein 26 III/IV 2097.]

6-Mercaptopurine monohydrate Upstream-Materialien And Downstream Produkte

6-Mercaptopurine monohydrate Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

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