Design of thymidylate synthase inhibitors using protein crystal structures: the synthesis and biological evaluation of a novel class of 5-substituted quinazolinones

…, V Kathardekar, KM Welsh, S Webber…

Index: Webber; Bleckman; Attard; Deal; Kathardekar; Welsh; Janson; Matthews; Smith; Freer; Jordan; Bacquet; Howland; Booth; Ward; Hermann; White; Morse; et al. Journal of Medicinal Chemistry, 1993 , vol. 36, # 6 p. 733 - 746

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Citation Number: 156

Abstract

The design, synthesis, and biological evaluation of a new class of inhibitors of thymidylate synthase (TS) is described. The molecular design was carried out by a repetitive crystallographic analysis of protein-ligand structures. At the onset of this project, we focused on the folate cofactor binding site of a high-resolution ternary crystal complex of Escherichia coli TS, 5'-fluorodeoxyuridylate (5-FdUMP) and a classical glutamate-containing folic acid ...