Synthesis and antitumor activity of 2,4-diamino-6-(2,5-dimethoxybenzyl)-5-methylpyrido[2,3-d]pyrimidine.

Basic Information

ID: ALA1121591

Journal: J Med Chem

Title: Synthesis and antitumor activity of 2,4-diamino-6-(2,5-dimethoxybenzyl)-5-methylpyrido[2,3-d]pyrimidine.

Authors: Grivsky EM, Lee S, Sigel CW, Duch DS, Nichol CA.

Abstract: The synthesis of 2,4-diamino-6-(2,5-dimethoxybenzyl)-5-methylpyrido[2,3-d]pyrimidine (BW301U, 7) by a route that has general applicability to the preparation of many 6-(substituted benzyl)-5-methylpyrido[2,3-d]pyrimidines is described. The key intermediate, 2,4-diamino-7,8-dihydro-6-(2,5-dimethoxybenzyl)-5-methyl-7-oxopyrido[2,3-d]pyrimidine (4), is converted to the 7-chloro compound 5 by treatment with a 1:1 complex of N,N-dimethylformamide--thionyl chloride, and 5 is hydrogenolyzed with palladium on charcoal in the presence of potassium hydroxide to yield 7. BW301U is a potent lipid-soluble inhibitor of mammalian dihydrofolate reductase and has significant activity against the Walker 256 carcinosarcoma in rats.

CiteXplore: 6928967

DOI: 10.1021/jm00177a025

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