title: Synthesis, biological activity, and absolute stereochemical assignment of NPS 1392: a potent and stereoselective NMDA receptor antagonist.
abstract: The synthesis, biological activity, and single crystal X-ray structure of NPS 1392, (R)-(-)-3,3-bis(3-fluorophenyl)-2-methylpropan-1-amine (3a), a potent, stereoselective antagonist of the NMDA receptor, are described. The NMDA receptor selectively bound the levo isomer (3a) over its enantiomer (3b), which prompted a rigorous absolute configuration assignment. NPS 1392 has the R configuration based on the single-crystal X-ray diffraction analysis of the hydroiodide salt of NPS 1392. This compound is a potential neuroprotective agent for use in the treatment of ischemic stroke.
authors.affiliation: NPS Pharmaceuticals, Inc., Salt Lake City, UT 84108, USA.
authors.forename: S T
authors.initials: ST
authors.lastname: Moe
authors.forename: S M
authors.initials: SM
authors.lastname: Shimizu
authors.forename: D L
authors.initials: DL
authors.lastname: Smith
authors.forename: B C
authors.initials: BC
authors.lastname: Van Wagenen
authors.forename: E G
authors.initials: EG
authors.lastname: DelMar
authors.forename: M F
authors.initials: MF
authors.lastname: Balandrin
authors.forename: Y
authors.initials: Y
authors.lastname: Chien
authors.forename: J L
authors.initials: JL
authors.lastname: Raszkiewicz
authors.forename: L D
authors.initials: LD
authors.lastname: Artman
authors.forename: A L
authors.initials: AL
authors.lastname: Mueller
authors.forename: E
authors.initials: E
authors.lastname: Lobkovsky
authors.forename: J
authors.initials: J
authors.lastname: Clardy
mesh_terms: D000818:Animals; D018360:Crystallography, X-Ray; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D007511:Ischemia / Q000188:drug therapy; D008958:Models, Molecular; D018696:Neuroprotective Agents / Q000494:pharmacology; D011407:Propane / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
chemical_list: D018691:Excitatory Amino Acid Antagonists; C121295:NPS 1392; D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D011407:Propane