Amino diacid 3, a highly selective competitive GluR5 kainate receptor antagonist, exhibited high GluR5 receptor affinity and selectivity over other glutamate receptors. Its diethyl ester prodrug 4 was orally active in two models of migraine: the neurogenic dural plasma protein extravasation model and the nucleus caudalis c-fos expression model. These data suggest that a GluR5 kainate receptor antagonist might be an efficacious antimigraine therapy with a novel mechanism of action.

Amino acids 5 and 7, two potent and selective competitive GluR5 KA receptor antagonists, exhibited high GluR5 receptor affinity over other glutamate receptors. Their ester prodrugs 6 and 8 were orally active in three models of pain: reversal of formalin-induced paw licking, carrageenan-induced thermal hyperalgesia, and capsaicin-induced mechanical hyperalgesia.

Strongly stabilized carbon nucleophiles such as dialkyl malonates can also attack the central carbon of (π‐allyl)palladium complexes. The regiochemistry of the reaction (attack at the terminal or C2 carbon atom; see picture) is controlled by the choice of the ligands L in the palladium complex. E = CO2Et, L = PPh3, PtBu3, P(OPh)3, etc.

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