Design, synthesis, and biological evaluation of simplified alpha-keto heterocycle, trifluoromethyl ketone, and formyl substituted folate analogues as potential inhibitors of GAR transformylase and AICAR transformylase

Bioorg Med Chem. 2003 Oct 1;11(20):4487-501. doi: 10.1016/s0968-0896(03)00456-5.

Abstract

A series of simplified alpha-keto heterocycle, trifluoromethyl ketone, and formyl substituted folate analogues lacking the benzoylglutamate subunit were prepared and examined as potential inhibitors of glycinamide ribonucleotide transformylase (GAR Tfase) and aminoimidazole carboxamide transformylase (AICAR Tfase).

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Drug Design
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / pharmacology
  • Folic Acid / analogs & derivatives*
  • Folic Acid / chemical synthesis
  • Folic Acid / pharmacology
  • Humans
  • Hydroxymethyl and Formyl Transferases / antagonists & inhibitors*
  • Inhibitory Concentration 50
  • Ketones
  • Phosphoribosylaminoimidazolecarboxamide Formyltransferase
  • Phosphoribosylglycinamide Formyltransferase
  • Structure-Activity Relationship

Substances

  • Enzyme Inhibitors
  • Ketones
  • Folic Acid
  • Hydroxymethyl and Formyl Transferases
  • Phosphoribosylglycinamide Formyltransferase
  • Phosphoribosylaminoimidazolecarboxamide Formyltransferase