Synthesis, 11C labeling and biological properties of derivatives of the tyrphostin AG957
| Autor: | John I. Sachinidis, Henri Tochon-Danguy, Andrew M. Scott, Uwe Ackermann, Edouard C. Nice, Maureen Nerrie |
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| Rok vydání: | 2004 |
| Předmět: |
Cancer Research
Schiff base Cell growth Stereochemistry Total synthesis Tyrphostins Quinone Benzaldehyde chemistry.chemical_compound chemistry Epidermal growth factor Cell culture Cell Line Tumor Isotope Labeling Leukemia Myelogenous Chronic BCR-ABL Positive Positron-Emission Tomography Molecular Medicine Humans Radiology Nuclear Medicine and imaging Carbon Radioisotopes Radiopharmaceuticals Tyrosine kinase Nuclear chemistry Cell Proliferation |
| Zdroj: | Nuclear medicine and biology. 32(4) |
| ISSN: | 0969-8051 |
| Popis: | Four analogues of AG957, a known inhibitor of the tyrosine kinase p210 bcr-abl , have been synthesized and tested for their growth inhibitory effect against the BCR/ABL-positive FDrv210C cells as well as the epidermal growth factor (EGF) receptor-positive Baf/ERX cells. All compounds that can undergo oxidation to the corresponding quinone demonstrated inhibition of FDrv210C cells and Baf/ERX cells. Compounds that cannot become oxidized showed significantly less inhibition of BCR/ABL- or EGF receptor-mediated cell proliferation. The 11 C-labeled compounds were prepared by labeling 4-aminobenzoic acid using [ 11 C]CH 3 I, which afforded the corresponding 11 C-labeled methyl ester in excellent yields. Subsequent condensation of the amino group with an appropriately substituted hydroxy benzaldehyde formed the respective Schiff base. Reduction of this compound with NaBH 3 CN gave the 11 C-labeled inhibitors in an overall radiochemical yield of 17.3±2.1% ( n =3; not decay corrected) and an average specific radioactivity of 40 GBq/µmol (1.1 Ci/µmol) at the end of synthesis. The total synthesis time from EOB including HPLC purification and formulation was 45 min. |
| Databáze: | OpenAIRE |
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