Synthesis and pharmacology of new enantiopure Δ3-4-arylkainoids

Seven Δ3-4-arylkainoids possessing various 4-position aromatic and heteroaromatic groups were synthesized and their apparent affinities were measured in order to explore the influences of 4-position electron density and stereochemistry on receptor affinity and specificity. Kainoids 1a–f were shown to be selective agonists at the NMDA receptor and the electron rich furanyl and thienyl analogues exhibited the highest affinities. Naphthylkainoid 1g proved to be a nonselective antagonist at the iGluRs. Scheme 1. Synthesis of (2S)-Δ3-4-Arylkainoids 1a–g.