Design of new analogues of glutamic acid with a conformationally restricted structure

Regioisomeric 3-carboxyisoxazolinyl prolines (CIP-A and CIP-B) and 3-hydroxyisoxazolinyl prolines [(±)-8 and (±)-9] were synthesized and assayed for glutamate receptor activity. CIP-A [(±)-6] showed a convulsant activity evaluated in vivo on DBA/2 mice, higher than AMPA and similar to kainic acid. The eutomer of CIP-A [CIP-AS, (-)-6], obtained from (S)-3,4-didehydroproline, evidenced common stereochemical requirements with AMPA and kainic acid. Copyright (C) 2000 Elsevier Science S.A.