Indole- and indoline-based kainate analogues with antagonist activity at ionotropic glutamate receptors.
Bioorganic & medicinal chemistry letters 2005 Sep 1; 15(17):3942-7
Shou X X, Miledi R R, Chamberlin A AR
Department of Chemistry, University of California, Irvine, CA 92697, USA.
A conformationally constrained, indole-based kainate analogue was designed based on Gouaux's X-ray structure of kainic acid bound to an iGluR2(S1S2) construct, a structural model for AMPA/kainate ionotropic glutamate receptors. In contrast to the parent kainic acid, a potent agonist, this compound, along with three structurally related analogues derived from synthetic intermediates, exhibited antagonist behavior towards KAR expressed in oocytes, a result that is rationalized by molecular modeling studies.

