Synthesis, biological activity, and absolute stereochemical assignment of NPS 1392: a potent and stereoselective NMDA receptor antagonist.
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.
Moe
S T
ST
NPS Pharmaceuticals, Inc., Salt Lake City, UT 84108, USA.
Shimizu
S M
SM
Smith
D L
DL
Van Wagenen
B C
BC
DelMar
E G
EG
Balandrin
M F
MF
Chien
Y
Y
Raszkiewicz
J L
JL
Artman
L D
LD
Mueller
A L
AL
Lobkovsky
E
E
Clardy
J
J
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*
D018691:Excitatory Amino Acid Antagonists; C121295:NPS 1392; D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D011407:Propane