Two non-polyglutamatable antifolates

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...

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544260, A61K 31505

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active

050735543

ABSTRACT:
Two new non-polyglutamatable glutamic acid derivatives in the antifolate series are provided as well as procedures for their preparation. These compounds are: 4-amino-4-deoxy-10-methylpteroyl-.tau.-methyleneglutamic acid (1) and 4-amino-4-deoxy-10-methylpteroyl-.beta.-hydroxyglutamic acid (2). Compounds 1 and 2 do not undergo polyglutamylation as determined by their inability to serve as substrates for folylpolyglutamate synthetase (FPGS), and they are powerful inhibitors of human dihydrofolate reductase (DHFR). Both compounds 1 and 2 are powerful inhibitors of the growth of Manca human lymphoma, human leukemia (CCRF-CEM) and H35 hepatoma cells.

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