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Temozolomide (Figure l), a novel imidazotetrazinonel, shows promising activity against gliomas and malignant melanomaz. It is believed that temozolomide is a pro-drug which accesses DNA and undergoes nucleophilic induced activation within the micro-environment of the major grove of DNA 1.3. This process is believed to consist of base promoted conversion to a methyltriazene with loss of the cabonyl group at position 4. The triazene then alkylates the nitrogen or oxygen of the central guanine of a three guanine sequence in the major grove of the DNA3.4. Symposium Abstracts min and [3-N-~~C-rnethyJltemozolomide (Va) at 14 min. The radiochemical yield of [3-N-Wrnethydtemozolomide was 510% from [11C]iodomethane. (iii) [4-~1C-curbonyCJTemozolomide (Vb). Cyclisation of [ N -11C-~urbony[lmethylisocyanate~ with the diazo precursor (IV) gave [4-11C-curbonyfJtemozoiomide (Vb) using the same reaction and purification conditions as above. In order to improve the yield from the cyclisation of the diazo precursor w i t h methylisocyanate, we are investigating the use of microwave heating. Reactions in DMSO were carried out in a CEM MDS-2000 microwave system using a fibreoptic temperature probe, a

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Publisher

John Wiley and Sons; Wiley (John Wiley & Sons); John Wiley & Sons Inc.; Wiley (ISSN 0022-2135)

Published

1994

Language

EN

Field

Medicine (Life Sciences)