Abstract：
:Enantiomeric propanolamines have been identified as a new class of NR2B-selective NMDA receptor antagonists. The most effective agents are biaryl structures, synthesized in six steps with overall yields ranging from 11-64%. The compounds are potent and selective inhibitors of NR2B-containing recombinant NMDA receptors with IC 50 values between 30-100 nM. Potency is strongly controlled by substitution on both rings and the centrally located amine nitrogen. SAR analysis suggests that well-balanced polarity and chain-length factors provide the greatest inhibitory potency. Structural comparisons based on 3D shape analysis and electrostatic complementarity support this conclusion. The antagonists are neuroprotective in both in vitro and in vivo models of ischemic cell death. In addition, some compounds exhibit anticonvulsant properties. Unlike earlier generation NMDA receptor antagonists and some NR2B-selective antagonists, the present series of propanolamines does not cause increased locomotion in rodents. Thus, the NR2B-selective antagonists exhibit a range of therapeutically interesting properties.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Tahirovic YA,Geballe M,Gruszecka-Kowalik E,Myers SJ,Lyuboslavsky P,Le P,French A,Irier H,Choi WB,Easterling K,Yuan H,Wilson LJ,Kotloski R,McNamara JO,Dingledine R,Liotta DC,Traynelis SF,Snyder JPdoi
10.1021/jm8002153subject
Has Abstractpub_date
2008-09-25 00:00:00pages
5506-21issue
18eissn
0022-2623issn
1520-4804journal_volume
51pub_type
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