Design and synthesis of noncompetitive metabotropic glutamate receptor subtype 5 antagonists

A series of diaryl amides was designed and synthesized as novel nonethynyl mGluR5 antagonists. The systematic variation of the pharmacophoric groups led to the identification of a lead compound that demonstrated micromolar affinity for the mGluR5. Further optimization resulted in compounds with impr...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2006-07, Vol.16 (13), p.3371-3375
Main Authors: Kulkarni, Santosh S., Nightingale, Barbara, Dersch, Christina M., Rothman, Richard B., Newman, Amy Hauck
Format: Article
Language:English
Subjects:
Amides - chemical synthesis
Amides - chemistry
Amides - pharmacology
Animals
Binding Sites - drug effects
Biological and medical sciences
Cattle
Crystallography, X-Ray
Drug Design
Drug Evaluation, Preclinical
Glutamatergic system (aspartate and other excitatory aminoacids)
In Vitro Techniques
Ligands
Medical sciences
Metabotropic glutamate receptor subtype 5
mGluR5
Models, Molecular
Molecular Structure
Neuropharmacology
Neurotransmitters. Neurotransmission. Receptors
Noncompetitive antagonists
Pharmacology. Drug treatments
Receptor, Metabotropic Glutamate 5
Receptors, Metabotropic Glutamate - antagonists & inhibitors
Stereoisomerism
Structure-Activity Relationship
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Summary:A series of diaryl amides was designed and synthesized as novel nonethynyl mGluR5 antagonists. The systematic variation of the pharmacophoric groups led to the identification of a lead compound that demonstrated micromolar affinity for the mGluR5. Further optimization resulted in compounds with improved binding affinities and antagonist profiles, in vitro.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2006.04.032