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.
Istituto di Chimica Farmaceutica e Tossicologica, Milan, Italy.
P
P
Conti
M
M
De Amici
C
C
De Micheli
D000818:Animals; D015195:Drug Design; D018690:Excitatory Amino Acid Agonists / Q000138:chemical synthesis / Q000494:pharmacology; D005971:Glutamates / Q000138:chemical synthesis* / Q000494:pharmacology; D051379:Mice; D008968:Molecular Conformation; D018091:Receptors, AMPA / Q000819:agonists; D018092:Kainic Acid Receptors / Q000819:agonists; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists; D013329:Structure-Activity Relationship
D018690:Excitatory Amino Acid Agonists; D005971:Glutamates; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate