55-98-1 Usage
Description
Busulfan is a chemically classified alkyl sulfonate that can cause DNA interstrand and intrastrand cross-linking through the displacement of methylsulfonate ester moieties by the nucleophilic N7 of guanine. It also exhibits cytotoxicity through alkylation of Cys sulfhydryl groups.
Used in Pharmaceutical Industry:
Busulfan is used as an antineoplastic alkylating agent for the palliative treatment of chronic myeloid leukemia and other myeloproliferative disorders. It is also used as an insect sterilant.
Used in Oncology:
Busulfan USP (Myleran) is utilized as a treatment for Chronic granulocytic leukemia, demonstrating its effectiveness in managing this specific type of cancer.
Originator
Myleran,Burroughs-
Wellcome,US,1954
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.
Manufacturing Process
3.6 grams of redistilled 1,4-butanediol were dissolved in 10 ml of pyridine and
the solution was cooled in ice and water. 9.6 grams of redistilled methanesulfonyl-
chloride were added dropwise at such a rate that the temperature did
not rise above 20°C. The solution was then allowed to stand at room
temperature to; 30 minutes, during which time the temperature rose to 60°C.
A thick precipitate of pyridine hydrochloride was formed.
The mass was cooled in ice water and was treated with 30 ml of ice cold
water. On agitation, a white crystalline precipitate was formed. This was
filtered off and washed well with ice cold water and allowed to drain on the
pump. It weighed 7.8 grams and had a melting point of 100°C. 3.5 grams of
the material were recrystallized from acetone and ether to give small white
needles, having a melting point of 106°-107°C, unchanged by further
recrystallization.
Therapeutic Function
Antineoplastic
Air & Water Reactions
Busulfan is an alkylating agent which hydrolyzes in water. .
Reactivity Profile
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.
Fire Hazard
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.
Side effects
Serious bone marrow hypoplasia and myelosuppression are possible with this agent, and recovery from busulfaninduced pancytopenia can take up to 2 years.
Safety Profile
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.
Synthesis
Busulfan, 1,4-butandioldimethansulfonate (30.2.3.1), is made by reacting
butandiol with methanesulfonyl chloride.
Veterinary Drugs and Treatments
Busulfan may be useful in the adjunctive therapy of chronic granulocytic
leukemias or polycythemia vera in small animals. Not commonly
used in veterinary medicine.
Drug interactions
Potentially hazardous interactions with other drugs
Antibacterials: concentration increased by
metronidazole.
Antipsychotics: avoid with clozapine, increased risk
of agranulocytosis.
Antifungals: metabolism inhibited by itraconazole,
monitor for signs of busulfan toxicity.
Carcinogenicity
1,4-Butanediol dimethanesulfonate is known to be a human carcinogen based on sufficient evidence of carcinogenicity from studies in
humans.
Metabolism
Busulfan is extensively metabolised in the liver, mainly
by conjugation with glutathione, either spontaneously or
mediated by the enzyme glutathione-S-transferase. About
12 inactive metabolites have been identified, which are
excreted in the urine. About 1% of busulfan is excreted
unchanged. Elimination in the faeces is considered to be
negligible.
references
[1]. probin v, wang y, zhou d. busulfan-induced senescence is dependent on ros production upstream of the mapk pathway. free radic biol med, 2007, 42(12): 1858-1865. [2]. probin v, wang y, bai a, et al. busulfan selectively induces cellular senescence but not apoptosis in wi38 fibroblasts via a p53-independent but extracellular signal-regulated kinase-p38 mitogen-activated protein kinase-dependent mechanism. j pharmacol exp ther, 2006, 319(2): 551-560.[3]. choi yj, ok dw, kwon dn, et al. murine male germ cell apoptosis induced by busulfan treatment correlates with loss of c-kit-expression in a fas/fasl- and p53-independent manner. febs lett, 2004, 575(1-3): 41-51.
Check Digit Verification of cas no
The CAS Registry Mumber 55-98-1 includes 5 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 2 digits, 5 and 5 respectively; the second part has 2 digits, 9 and 8 respectively.
Calculate Digit Verification of CAS Registry Number 55-98:
(4*5)+(3*5)+(2*9)+(1*8)=61
61 % 10 = 1
So 55-98-1 is a valid CAS Registry Number.
InChI:InChI=1/C6H14O6S2/c1-13(7,8)11-5-3-4-6-12-14(2,9)10/h3-6H2,1-2H3
55-98-1Relevant articles and documents
Busulfan drug intermediate 1,4 bis-methyl sulfonate butyl diester synthetic method
-
Paragraph 0014; 0015, (2016/10/10)
A busulfan drug intermediate 1,4-bis-methyl sulfonate butyl diester synthetic method comprises the following steps: 0.15mol of 1,4-butanediol and 150-170ml of triethylamine are added into a reaction vessel, solution temperature is reduced to 3-5 DEG C, stirring speed is controlled at 130-160rpm, 0.36-0.38mol of methanesulfonic acid amine is slowly dropwise added, after the completion of the dropwise addition, the solution temperature is raised to 35-40 DEG C, the solution is stirred for 3-4h, solution temperature is reduced to 15-20 DEG C, a solid is precipitated, and the solid is filtered, washed with a saline solution, dehydrated with a dehydrating agent, and recrystallized in cyclohexane to obtain a white solid of 1,4-bis-methyl sulfonate butyl diester; and the saline solution in the step is any one of sodium nitrate and potassium sulphate.
DITHIOAMINE REDUCING AGENTS
-
Page/Page column, (2013/08/28)
Dithioamine reducing agents useful for the reduction of disulfide bonds. The reducing agents of this invention are useful, for example, to reduce disulfide bonds, particularly in proteins, or to prevent the formation of disulfide bonds, particularly in proteins and other biological molecules. Reducing agents of this invention are useful and suitable for application in a variety of biological applications, particularly as research and synthetic reagents. The invention provides S-acylated dithioamines which can be selectively activated reducing agents by removal of the S-acyl groups enzymatically or chemically. The invention further provides dithiane precursors of thioamino reducing agents. The invention provides dithioamine reducing agents, S-acylated dithioamines and dithianes which are immobilized on surfaces, including among others, glass, quartz, microparticles, nanoparticles and resins.
THERAPEUTIC FOR HEPATIC CANCER
-
, (2011/02/18)
A novel pharmaceutical composition for treating or preventing hepatocellular carcinoma and a method of treatment are provided. A pharmaceutical composition for treating or preventing liver cancer is obtained by combining a chemotherapeutic agent with an anti-glypican 3 antibody. Also disclosed is a pharmaceutical composition for treating or preventing liver cancer which comprises as an active ingredient an anti-glypican 3 antibody for use in combination with a chemotherapeutic agent, or which comprises as an active ingredient a chemotherapeutic agent for use in combination with an anti-glypican 3 antibody. Using the chemotherapeutic agent and the anti-glypican 3 antibody in combination yields better therapeutic effects than using the chemotherapeutic agent alone, and mitigates side effects that arise from liver cancer treatment with the chemotherapeutic agent.