Enantiomers of 2-[(acylamino)ethyl]-1,4-benzodiazepines, potent ligands ofkappa-opioid receptor: Chiral chromatographic resolution, configurational assignment, and biological activity

Compounds 2a and 3a-e are racemic 2-[(acylamino)ethyl]-1,4-benzodiazepines, tifluadom analogs, with high affinity and selectivity towards the kappa -o pioid receptor. We describe the enantiomeric separation of all compounds th rough liquid chromatography with chiral stationary phases, as well as the r esolution of the enantiomers of the most interesting compounds, 2a and 3a, by the semipreparative column Chiralpak AD. The configuration of the resolv ed enantiomers was investigated: the comparative study of CID and H-1 NMR s pectra shows that compounds (-)-2a and (-)-3a have the same absolute config uration of (+)-(S)-tifluadom. A study on the stereoselective interaction wi th opiate receptors is reported. Chirality 13:606-612, 2001. (C) 2001 Wiley -Liss, Inc.