| 摘要 |
<p>Three new non-polyglutamatable glutamic acid derivatives in the antifolate series are provided as well as procedures for their preparation. These compounds are: 4-amino-acid-4-deoxy-10-deazapteroyl-η-methyleneglutamic acid, (1); 4-amino-4-deoxy-10-ethyl-10-deazapteroyl-η-methyleneglutamic acid (2); and 4-amino-4-deoxy-10-deazapteroyl-3-hydroxyglutamic acid (3). None of the compounds undergo polyglutamylation as determined by their inability to serve as substrates for folylpolyglutamate synthetase (FPGS). Compounds (1) and (2) are transported more effectively to tumour cells and they are more powerful in inhibiting the growth of human leukaemia cells in culture as compared to the standard anticancer drug methotrexate. All three compounds (1, 2, and 3) inhibit human dihydrofolate reductase to the same extent as methotrexate.</p> |
