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

Academic Article
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related to degree

  • Haynes, Nancy-Ellen, Ph.D. in Organic Chemistry, Scripps Research 1991 - 1996

publication date

  • September 1997

abstract

  • 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 microM) and more modest inhibition of AICAR Tfase (Ki = 42 +/- 11 microM).