A novel class of AMPA receptor allosteric modulators. Part 1: Design, synthesis, and SAR of 3-aryl-4-cyano-5-substituted-heteroaryl-2-carboxylic acid derivatives

The synthesis and initial SAR studies of novel, highly potent positive allosteric modulators of AMPA receptors based on 3-(4- tert-butylphenyl)-4-cyano-5-methylsulfanyl-thiophene-2-carboxylic acid ( 6a) are described. The synthesis and initial SAR studies of novel, highly potent positive allosteric...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2006-10, Vol.16 (19), p.5057-5061
Main Authors: Fernandez, Maria-Carmen, Castaño, Ana, Dominguez, Esteban, Escribano, Ana, Jiang, Delu, Jimenez, Alma, Hong, Eric, Hornback, William J., Nisenbaum, Eric S., Rankl, Nancy, Tromiczak, Eric, Vaught, Grant, Zarrinmayeh, Hamideh, Zimmerman, Dennis M.
Format: Article
Language:English
Subjects:
Allosteric Regulation
AMPA receptor allosteric modulators
Biological and medical sciences
Carboxylic Acids
Drug Design
Excitatory Amino Acid Agents - chemical synthesis
Excitatory Amino Acid Agents - pharmacology
Glutamatergic system (aspartate and other excitatory aminoacids)
Heteroaryl carboxylic acids
Heterocyclic Compounds - chemical synthesis
Heterocyclic Compounds - pharmacology
Humans
Medical sciences
Neuropharmacology
Neurotransmitters. Neurotransmission. Receptors
Pharmacology. Drug treatments
Receptors, AMPA - drug effects
Structure-Activity Relationship
Sulfides
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Summary:The synthesis and initial SAR studies of novel, highly potent positive allosteric modulators of AMPA receptors based on 3-(4- tert-butylphenyl)-4-cyano-5-methylsulfanyl-thiophene-2-carboxylic acid ( 6a) are described. The synthesis and initial SAR studies of novel, highly potent positive allosteric modulators of AMPA receptors based on 3-(4- tert-butylphenyl)-4-cyano-5-methylsulfanyl-thiophene-2-carboxylic acid ( 6a) are described. SAR studies at the thioether moiety indicated that substitution at this position was mandatory and better potency was achieved with small groups.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2006.07.035