1,4-Butandiol-dimethylsulfonat Chemische Eigenschaften,Einsatz,Produktion Methoden
R-Sätze Betriebsanweisung:
R45:Kann Krebs erzeugen.
R26/27/28:Sehr giftig beim Einatmen, Verschlucken und Berührung mit der Haut.
R63:Kann das Kind im Mutterleib möglicherweise schädigen.
R46:Kann vererbbare Schäden verursachen.
R36/37/38:Reizt die Augen, die Atmungsorgane und die Haut.
R23/24/25:Giftig beim Einatmen, Verschlucken und Berührung mit der Haut.
S-Sätze Betriebsanweisung:
S53:Exposition vermeiden - vor Gebrauch besondere Anweisungen einholen.
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).
Beschreibung
Chemically, busulfan is classified as an alkyl sulfonate. One or both of the methylsulfonate ester moieties can be displaced by the nucleophilic N7 of guanine, leading to monoalkylated and cross-linked DNA. The extent of alkyl sulfonate–mediated DNA interstrand cross-linking has been shown to vary with the length of the alkyl chain between sulfonate esters, with the tetramethylene-containing busulfan showing less interstrand cross-linking capability than hexamethylene, methylene, or octamethylene analogues. Intrastrand cross-linking also occurs, preferentially at 5′-GA-3′ but also at 5′-GG-3′ sequences. Alkylation of Cys sulfhydryl groups is yet another mechanism of cytotoxicity.
Chemische Eigenschaften
White Crystalline Solid
Verwenden
Busulfan USP (Myleran) is used to treat Chronic granulocytic leukemia; other myeloproliferative disorders.
Indications
Busulfan (Myleran) is a bifunctional methanesulfonic
ester that forms intrastrand cross-linkages with DNA.
The drug is well absorbed after oral administration and
has a plasma half-life of less than 5 minutes. Metabolites
and degradation products are excreted primarily in the
urine.
Busulfan is used in the palliative treatment of
chronic granulocytic leukemia. Daily oral therapy results
in decreased peripheral white blood cells and improved
symptoms in almost all patients during the
chronic phase of the disease. Excessive uric acid production
from rapid tumor cell lysis should be prevented
by coadministration of allopurinol.
At usual therapeutic dosages, busulfan is selectively
toxic to granulocyte precursors rather than lymphocytes.
Thrombocytopenia and anemia and less commonly,
nausea, alopecia, mucositis, and sterility also may
occur. Unusual side effects of busulfan include gynecomastia,
a general increase in skin pigmentation, and interstitial
pulmonary fibrosis.
Definition
ChEBI: A methanesulfonate ester that is butane-1,4-diol in which the hydrogens of the hydroxy groups are replaced by methanesulfonyl groups. An alkylating antineoplastic agent, it is used for the treatment of chronic myeloid leukemia (although it has been largely
replaced by newer drugs). It is also used as an insect sterilant.
Allgemeine Beschreibung
As an alternative to utilizing aziridines as electrophilic species,it was found that simply utilizing a carbon chain terminated atboth ends by leaving groups gave compounds capable of actingas cross-linking agents.Busulfan utilizestwo sulfonate functionalities as leaving groups separated by afour-carbon chain that reacts with DNA to primarily form intrastrandcross-link at 5'-GA-3' sequences.The sulfonatesare also subject to displacement by the sulfhydryl functionsfound in cysteine and glutathione, and metabolic products areformed as a result of nucleophilic attack by these groups togenerate sulfonium species along with methane sulfonicacid.This is followed by conversion to tetrahydrothiophene,and further oxidation products are subsequently produced togive the sulfoxide and sulfone. The cyclic sulfone known assulfolane may be further oxidized to give 3-hydroxysulfolane.
Air & Water Reaktionen
Busulfan is an alkylating agent which hydrolyzes in water. .
Reaktivität anzeigen
Busulfan is an alkylating agent which hydrolyzes in water. . Strong reducers may yield hydrogen sulfide.
Hazard
Extremely toxic, carcinogen, clastogenic,
teratogenic, immunosuppressive, delayed bone
marrow aplasia, cataracts, pigmentation, pulmonary
thrombosis, cardiotoxic effects, thrombocytopenia.
Brandgefahr
Flash point data for Busulfan are not available. Busulfan is probably combustible.
Clinical Use
Busulfan is used in the treatment of chronic myelogenous leukemia and can be administered either orally or by IV infusion.
Nebenwirkungen
Serious bone marrow hypoplasia and myelosuppression are possible with this agent, and recovery from busulfaninduced pancytopenia can take up to 2 years.
Sicherheitsprofil
Confirmed carcinogen
producing leukemia, kidney, and uterine
tumors. Experimental neoplastigenic and
tumorigenic data. Poison by ingestion,
subcutaneous, intraperitoneal, intravenous,
and possibly other routes. Ingestion by
pregnant women can cause cancer of the
reproductive system of the fetus includtng
the uterus. Human teratogenic effects by
ingestion and possibly other routes include
developmental abnormaltties of the eye, ear,
craniofacial area including the nose and
tongue, gastrointestinal system, endocrine
system, urogenital system, and other
unspecified areas. Other human
reproductive effects by ingestion and
possibly other routes include: impotence,
changes in the uterus, cervix, and vagina,
and menstrual-cycle dtsorders. Experimental
reproductive effects. Human systemic
effects by ingestion: general arteriolar or
venous ddation of the eye, changes in
structure or function of salivary glands.
When heated to decomposition it emits
toxic fumes of SOx. See also
SULFONATES.
Carcinogenicity
1,4-Butanediol dimethanesulfonate is known to be a human carcinogen based on sufficient evidence of carcinogenicity from studies in
humans.
1,4-Butandiol-dimethylsulfonat Upstream-Materialien And Downstream Produkte
Upstream-Materialien
Downstream Produkte
