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Updated: Feb 21, 2026

A High-content Assay for Monitoring AMPA Receptor Trafficking
Published on: January 28, 2019
Discovery of 3-substituted aminocyclopentanes as potent and orally bioavailable NR2B subtype-selective NMDA
Mark E Layton1, Michael J Kelly, Kevin J Rodzinak
1Departments of Medicinal Chemistry, Merck Research Laboratories, West Point, Pennsylvania 19486, USA. mark_layton@merck.com
Abstract:
A series of 3-substituted aminocyclopentanes has been identified as highly potent and selective NR2B receptor antagonists. Incorporation of a 1,2,4-oxadiazole linker and substitution of the pendant phenyl ring led to the discovery of orally bioavailable analogues that showed efficient NR2B receptor occupancy in rats. Unlike nonselective NMDA antagonists, the NR2B-selective antagonist 22 showed no adverse affects on motor coordination in the rotarod assay at high dose. Compound 22 was efficacious following oral administration in a spinal nerve ligation model of neuropathic pain and in an acute model of Parkinson's disease in a dose dependent manner.
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