ABENZYL 10-FORMYL-TRIDEAZAFOLIC ACID (ABENZYL 10-FORMYL-TDAF) - AN EFFECTIVE INHIBITOR OF GLYCINAMIDE RIBONUCLEOTIDE TRANSFORMYLASE

The synthesis of quinazolin-6-yl)-6-formyl-1-oxo-heptyl]-L-glutamic ac id (2, abenzyl 10-formyl-5,8,10-trideazafolic acid) as a potential enz yme-assembled tight binding inhibitor of glycinamide ribonucleotide tr ansformylase (GAR Tfase) or aminoimidazole carboxamide ribonucleotide transformylase (AICAR Tfase) is reported. The inhibitor was prepared b y a convergent synthesis utilizing the sequential alkylations of aceta ldehyde dimethylhydrazone with 6 and 8. The agent exhibited effective inhibition of GAR Tfase (K-i = 4.5 +/- 0.3 mu M) and more modest inhib ition of AICAR Tfase (K-i = 42 +/- 11 mu M). (C) 1997 Elsevier Science Ltd.