NR2B-selective N-methyl-D-aspartate antagonists: synthesis and evaluation of 5-substituted benzimidazoles

  • J Med Chem. 2004 Apr 8;47(8):2089-96. doi: 10.1021/jm030483s.
John A McCauley  1 ,  Cory R Theberge ,  Joseph J Romano ,  Susan B Billings ,  Kenneth D Anderson ,  David A Claremon ,  Roger M Freidinger ,  Rodney A Bednar ,  Scott D Mosser ,  Stanley L Gaul ,  Thomas M Connolly ,  Cindra L Condra ,  Menghang Xia ,  Michael E Cunningham ,  Bohumil Bednar ,  Gary L Stump ,  Joseph J Lynch ,  Alison Macaulay ,  Keith A Wafford ,  Kenneth S Koblan ,  Nigel J Liverton
Affiliations
  • 1. Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA. [email protected]
PMID: 15056006 DOI: 10.1021/jm030483s
Abstract

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 Alpha(1)-adrenergic binding. Benzimidazole 37a shows excellent activity in the carrageenan-induced mechanical hyperalgesia assay in rats as well as good pharmacokinetic behavior in dogs.

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