Quinoline-2,4-dicarboxylic acids: Synthesis and evaluation as inhibitors of the glutamate vesicular transport system

Twenty-six quinoline-2,4-dicarboxylic acids (QDCʹs) were synthesized by a modified Doebner-von Miller pathway and tested as inhibitors against the glutamate vesicular transport (GVT) protein. The QDCʹs were active as inhibitors with the most potent QDCʹs found to contain halogens at the 6-/8-position, a hydroxyl at the 8-position, or a tethered aromatic moiety at the 6- or 7-position of the quinoline.