124638-90-0Relevant academic research and scientific papers
Latent Inhibitors. Part 5. Latent Inhibition of Dihydrofolate Reductase by a Pteridine-spiro-cyclopropane
Haddow, John,Suckling, Colin J.,Wood, Hamish C. S.
, p. 1297 - 1304 (2007/10/02)
The design of cyclopropane-containing enzyme activated inhibitors of dihydrofolate reductase is presented.The synthesis of two examples, 2-amino-7,8-dihydro-6-hydroxymethylpteridine-7-spirocyclopropan-4(3H)-one and 2,4-diamino-5-(4-chlorophenyl)-6-cyclopropylpyrimidine, is described.Kinetic studies with dihydrofolate reductase from E. coli are presented to show that the former is a time-dependent inhibitor of the enzyme whereas the latter is a typical competitive inhibitor.The results are interpreted with regard to the active site structure of dihydrofolate reductase.
