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NR2B-Selective N-Methyl-d-aspartate Antagonists:  Synthesis and Evaluation of 5-Substituted Benzimidazoles

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Departments of Medicinal Chemistry, Molecular Pharmacology, and Pharmacology, Merck Research Laboratories, West Point, Pennsylvania 19486
Cite this: J. Med. Chem. 2004, 47, 8, 2089–2096
Publication Date (Web):March 11, 2004
https://doi.org/10.1021/jm030483s
Copyright © 2004 American Chemical Society

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    Abstract

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    Two classes of 5-substituted benzimidazoles were identified as potent antagonists of the NR2B subtype of the N-methyl-d-aspartate (NMDA) receptor. Selected compounds show very good selectivity versus the NR2A, NR2C, and NR2D subtypes of the NMDA receptor as well as versus hERG-channel activity and α1-adrenergic binding. Benzimidazole 37a shows excellent activity in the carrageenan-induced mechanical hyperalgesia assay in rats as well as good pharmacokinetic behavior in dogs.

    *

     To whom correspondence should be addressed. Phone:  215-652-4133. Fax:  215-652-3971. E-mail:  [email protected].

     Department of Medicinal Chemistry.

     Department of Molecular Pharmacology.

     Department of Pharmacology.

    #

     Department of Pharmacology, Merck Sharp & Dohme Research Laboratories, The Neuroscience Research Centre, Terlings Park, Eastwick Road, Harlow, Essex, CM20 2QR, UK.

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