Design and synthesis of noncompetitive metabotropic glutamate receptor subtype 5 antagonists

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Abstract

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.

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Acknowledgments

S.S.K. was supported by a NIH-visiting fellowship, B.N. was supported by a post-baccalaureate IRTA fellowship. Functional assay data were provided by the National Institute on Mental Health-Psychoactive Drug Screening Program (PDSP) with special thanks to Drs. Linda Brady and Bryan Roth for their support. Also, the authors wish to acknowledge Dr. Jarda Wroblewski for his contributions through the PDSP contract and thoughtful discussion of the functional assay results. This work is supported by

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