Chiral synthesis and pharmacological evaluation of NPS 1407 : A potent, stereoselective NMDA receptor antagonist

Abstract The stereoselective synthesis and biological activity of NPS 1407 ( 4a ), ( S )-(−)-3-amino-1,1-bis(3-fluorophenyl)butane, a potent, stereoselective antagonist of the NMDA receptor, are described. The racemate ( 4 ) was found to be active at the NMDA receptor in an in vitro assay, prompting the synthesis of the individual stereoisomers. The S isomer ( 4a ) was found to be 12 times more potent than the R isomer ( 4b ). Compound 4a demonstrated in vivo pharmacological activity in neuroprotection and anticonvulsant assays.