New aromatic inhibitors of EPSP synthase incorporating hydroxymalonates as novel 3-phosphate replacements

A Shah, JL Font, MJ Miller, JE Ream, MC Walker…

Index: Shah, Ajit; Font, Jose L.; Miller, Michael J.; Ream, Joel E.; Walker, Mark C.; Sikorski, James A. Bioorganic and Medicinal Chemistry, 1997 , vol. 5, # 2 p. 323 - 334

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Citation Number: 8

Abstract

A new, aromatic analogue of the EPSP synthase enzyme reaction intermediate 1 has been identified, which contains a 3-hydroxymalonate moiety in place of the usual 3-phosphate group. This simplified inhibitor was readily prepared in five steps from ethyl 3, 4- dihydroxybenzoate. The resulting tetrahedral intermediate mimic 9 is an effective, competitive inhibitor versus S3P with an apparent Ki of 0.57±0.06 μM. This result ...