Add time:07/13/2019         Source:sciencedirect.com

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 transformylase (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 (Ki = 4.5 ± 0.3 μM) and more modest inhibition of AICAR Tfase (Ki = 42 ± 11 μM).

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