Synthesis and biological evaluation of fenobam analogs as mGlu5 receptor antagonists

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Abstract

Optimization of affinity and microsomal stability led to identification of the potent, metabolically stable fenobam analog 4l. Robust in vivo efficacy of 4l was demonstrated in four different models of anxiety. Additionally, a ligand based pharmacophore alignment of fenobam and MPEP is proposed.

Graphical abstract

Optimization of affinity and microsomal stability led to identification of the potent, metabolically stable fenobam analog 4l. Robust in vivo efficacy of 4l was demonstrated in four different models of anxiety. Additionally, a ligand based pharmacophore alignment of fenobam and MPEP is proposed.

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Acknowledgments

The excellent technical assistance of Daniel Rueher, Antonio Ricci, Francoise Kahn, Severine Weil-Bandinelli, and Sean Durkin is gratefully acknowledged.

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