Synthesis of Naphthoic Acids as Potential Anticancer Agents

As part of ongoing research to investigate structural requirements for lactate dehydrogenase inhibition by highly substituted naphthoic acids, nine new aryl-substituted dihydroxynaphthoic acids were synthesized from three known precursors. Described here are efficient preparations of the 1-naphthoic acid target compounds by using Suzuki coupling reactions, formylations, oxidations, and demethylations. Lactate dehydrogenase inhibition studies conducted with five of the compounds revealed values of the inhibitory constant K-i in the low micromolar range.