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Methylating Agent (methylating + agent)

Distribution by Scientific Domains

Chemistry	85%

Selected Abstracts

An Environmentally Benign Access to Dimethylated 1,6-Dihydropyrimidines Using Dimethyl Carbonate as Methylating Agent under Microwave

CHINESE JOURNAL OF CHEMISTRY, Issue 2 2008
Xi-Cun WANG
Abstract An environmentally benign procedure for dimethylated 1,6-dihydropyrimidines has been developed by the reaction of 1,2,3,4-tetrahydropyrimidine-2-thiones with dimethyl carbonate, a non-toxic and environmentally friendly reagent. The methylation of 1,2,3,4-tetrahydropyrimidine-2-thione was promoted by MgO and tetrabutylammonium bromide (TBAB) under microwave. This protocol avoids the use of strong bases and highly toxic methylating agents such as methyl halide or dimethyl sulfate. Additionally, the possible role of MgO/TBAB in the reaction was also presented. [source]

Methyl Orthocarboxylates as Methylating Agents of Heterocycles.

CHEMINFORM, Issue 39 2002
Yves L. Janin
Abstract For Abstract see ChemInform Abstract in Full Text. [source]

Fully automated high yield synthesis of (R)- and (S)-[11C]verapamil for measuring P-glycoprotein function with positron emission tomography

JOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 14 2002
Gert Luurtsema
Abstract Racemic (±) verapamil is a well characterized substrate for P-glycoprotein (P-gp). However, the in vivo pharmacokinetics and pharmacodynamics of both enantiomers are reported to be different. In the preparation of evaluation studies of both enantiomers in animals and humans, the purpose of the present study was to optimize and automate the synthesis of (R)- and (S)-[11C]verapamil. (R)- and (S)-[11C]verapamil were prepared from (R)- and (S)-desmethyl-verapamil, respectively, by methylation with no-carrier added [11C]methyliodide or [11C]methyltriflate. Different conditions of the methylation reaction were studied: reaction time, temperature, base and solvent, and chemical form of the precursor using either the hydrochloric acid salt or the free base of the starting material. After optimization, the synthesis was fully automated using home-made modules and performed according to GMP guidelines. Optimal yields of 60,70% for the methylation reaction were obtained using 1.5 mg of the free base of (R)- or (S)-desmethyl-verapamil in 0.5 ml of acetonitrile at 50°C for 5 min with [11C]methyltriflate as methylating agent. Under the same reaction conditions, but with a reaction temperature of 100°C, the radiochemical yield starting with [11C]methyliodide as methylation reagent was 40%. The specific activity of (R)- and (S)-[11C]verapamil was >20 GBq/,mol and the radiochemical purity was >99% for both methods. The total synthesis time was 45 min. The automated high yield synthesis of (R)- and (S)-[11C]verapamil provides the means for evaluating both enantiomers as in vivo tracers of P-gp function. Copyright © 2002 John Wiley & Sons, Ltd. [source]

Determination of organic acids in urine by solid-phase microextraction and gas chromatography,ion trap tandem mass spectrometry previous ,in sample' derivatization with trimethyloxonium tetrafluoroborate

BIOMEDICAL CHROMATOGRAPHY, Issue 10 2008
Marco Pacenti
Abstract A method for the determination of the organic acids directly in the urine employing derivatization with trimethyloxonium tetrafluoroborate as a methylating agent and sequential extraction by head space and direct immersion/solid phase microextraction is reported. Furoic acid, hippuric acid, methylhippuric acid, mandelic acid, phenylglyoxylic acid and trans, trans muconic acid contained in urine and proposed by the American Conference of Governmental Industrial Hygienists as biological exposure indices were determined after a fast and economically convenient preparation step and sensitive gas chromatography,ion trap,mass spectrometry/tandem mass spectrometry analysis. Urine is rather a complex sample and hence the acquisition method required specific GC-MS instrumentation capable of supporting the changeover, fully automated during a single chromatographic separation, from mass to tandem mass spectrometry and both chemical and electron ionization modes. The automation of the analytical method provides a number of advantages, including reduced analysis time for both routine analysis and method development, and greater reproducibility. The equilibrium and kinetics of this substances vs head space/direct immersion-solid phase microextraction were investigated and evaluated theoretically. Copyright © 2008 John Wiley & Sons, Ltd. [source]

Multi-institutional phase II study of temozolomide administered twice daily in the treatment of recurrent high-grade gliomas,

CANCER, Issue 5 2008
Casilda Balmaceda MD
Abstract BACKGROUND. The prognosis for patients with recurrent high-grade gliomas is poor and treatment options are limited. Current chemotherapeutic regimens can improve clinical outcomes, but extend survival by only a few months. Temozolomide is a methylating agent that is typically administered once daily. Because preclinical studies suggested that a twice-daily dosing schedule might be more effective, the safety and efficacy of twice-daily dosing of temozolomide were studied in patients with recurrent gliomas at their first, second, or third recurrence. METHODS. This multi-institutional trial enrolled 120 patients with recurrent glioblastoma multiforme (GBM), anaplastic astrocytoma (AA), or anaplastic oligodendroglioma (AO). An initial oral dose of 200 mg/m2 of temozolomide was followed by 9 consecutive doses of 90-mg/m2 every 12 hours. Treatment cycles were repeated every 28 days. Doses were escalated to 100 mg/m2 twice daily in the absence of unacceptable toxicity or were reduced if unacceptable toxicity occurred. RESULTS. For GBM, AA, and AO patients, respectively, the median progression-free survival (PFS) was 4.2 months, 5.8 months, and 7.7 months, whereas the median overall survival (OS) was 8.8 months, 14.6 months, and 18 months. The overall response rate (partial and complete) for the GBM, AA, and AO patients was 31%, 46%, and 46%, respectively. Grade 3/4 toxicities included neutropenia (1.1%), thrombocytopenia (3.6%), and anemia (0.3%) (graded according to the World Health Organization grading system). CONCLUSIONS. Twice-daily dosing may enhance the efficacy of temozolomide in the treatment of recurrent gliomas without increasing toxicity. This regimen compares favorably with other dosing schedules of temozolomide reported in the literature. Cancer 2008. © 2008 American Cancer Society. [source]

Activation barriers for DNA alkylation by carcinogenic methane diazonium ions

JOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 3 2006
Kaushalya S. Ekanayake
Abstract Methylation reactions of the DNA bases with the methane diazonium ion, which is the reactive intermediate formed from several carcinogenic methylating agents, were examined. The SN2 transition states of the methylation reactions at N7, N3, and O6 of guanine; N7, N3, and N1 of adenine; N3 and O2 of cytosine; and O2 and O4 of thymine were calculated using the B3LYP density functional method. Solvation effects were examined using the conductor-like polarizable continuum method and the combined discrete/SCRF method. The transition states for reactions at guanine N3, adenine N7, and adenine N1 are influenced by steric interactions between the methane diazonium ion and exocyclic amino groups. Both in the gas phase and in aqueous solution, the methylation reactions at N atoms have transition states that are looser, and generally occur earlier along the reaction pathways than reactions at O atoms. The forming bonds in the transition states in water are 0.03 to 0.13 Å shorter than those observed in the gas phase, and the activation energies are 13 to 35 kcal/mol higher. The combined discrete/SCRF solvation energy calculations using base-water complexes with three water molecules yield base solvation energies that are larger than those obtained from the CPCM continuum method, especially for cytosine. Reactivities calculated using barriers obtained with the discrete/SCRF method are consistent with the experimentally observed high reactivity at N7 of guanine. © 2005 Wiley Periodicals, Inc. J Comput Chem 27: 277,286, 2006 [source]