Design, synthesis, and biological evaluation of a scaffold for iGluR ligands based on the structure of (-)-dysiherbaine.
The design and synthesis of four 2,2-disubstituted dihydrobenzofurans that are structurally related to several glutamate-containing natural products, including (-)-dysiherbaine, is described. Biological evaluation of these analogs shows that one is a KA receptor antagonist and another is an NMDA receptor agonist.
Cohen
Jamie L
JL
Department of Chemistry, University of California at Irvine, Irvine, CA 92697, USA.
Limon
Agenor
A
Miledi
Ricardo
R
Chamberlin
A Richard
AR
D000409:Alanine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D001572:Benzofurans / Q000138:chemical synthesis* / Q000494:pharmacology; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000737:chemistry* / Q000494:pharmacology; D002540:Cerebral Cortex / Q000378:metabolism; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D008024:Ligands; D051381:Rats; D017470:Receptors, Glutamate / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists*; D013329:Structure-Activity Relationship
D001572:Benzofurans; D019086:Bridged Bicyclo Compounds, Heterocyclic; D018691:Excitatory Amino Acid Antagonists; D008024:Ligands; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; C121741:dysiherbaine; D000409:Alanine