5-p-Benzoquinonyl-2'-deoxyuridine 5'-phosphate: a possible mechanism-based inhibitor of thymidylate synthetase

L Maggiora, CTC Chang, ME Hasson…

Index: Maggiora; Chang; Hasson; Bigge; Mertes Journal of Medicinal Chemistry, 1983 , vol. 26, # 7 p. 1028 - 1036

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Citation Number: 8

Abstract

The title compound (l), designed as a suicide inhibitor of thymidylate synthetase, can be prepared by silver (I1) oxide oxidative demethylation of the corresponding dimethoxyphenyl derivative. Compound 1 shows time-dependent inactivation of thymidylate synthetase (methotrexate-resistant Lactobacillus casei) and saturation kinetics, and the inactivation is responsive to substrate protection. The inactivation is not reversible on prolonged dialysis ...