Abenzyl 10-formyl-trideazafolic acid (abenzyl 10-formyl-TDAF): An effective inhibitor of glycinamide ribonucleotide transformylase

The synthesis of N-[7-(2-amino-3,4-dihydro-4-oxo-quinazolin-6-yl)-6-formyl-1-oxo-heptyl]-L -glutamic acid (2, abenzyl 10-formyl-5,8,10-trideazafolic acid) as a potential enzyme-assembled tight binding inhibitor of glycinamide ribonucleotide transformylase (GAR Tfase) or aminoimidazole carboxamide ribonucleotide fransformylase (AICAR Tfase) is reported. The inhibitor was prepared by a convergent synthesis utilizing the sequential alkylations of acetaldehyde dimethylhydrazone with 6 and 8. The agent exhibited effective inhibition of GAR Tfase (K(i) = 4.5 ± 0.3 μM) and more modest inhibition of AICAR Tfase (K(i) = 42 ± 11 μM).