| Literature DB >> 22816022 |
Mark E Layton1, Michael J Kelly, Kevin J Rodzinak, Philip E Sanderson, Steven D Young, Rodney A Bednar, Anthony G Dilella, Terrence P McDonald, Hao Wang, Scott D Mosser, John F Fay, Michael E Cunningham, Duane R Reiss, Christine Fandozzi, Nicole Trainor, Annie Liang, Edward V Lis, Guy R Seabrook, Mark O Urban, James Yergey, Kenneth S Koblan.
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.Entities:
Keywords: NMDA; NR2B antagonist; Parkinson’s disease; neuropathic pain
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Year: 2011 PMID： 22816022 PMCID： PMC3369735 DOI： 10.1021/cn200013d
Source DB: PubMed Journal: ACS Chem Neurosci ISSN： 1948-7193 Impact factor: 4.418