Serotonin 5-HT4 receptor agonistic activity of the optical isomers of (±)-4-amino-N-[2-(1-azabicyclo[3.3.0]octan-5-yl)ethyl]-5-chloro-2,3-dihydro- 2-methylbenzo[b]furan-7-carboxamide

Abstract

The enantiomers, (R)-(-)-1 and (S)-(+)-1, of (±)-4-amino-N-[2-(1- azabicyclo[3.3.0]octan-5-yl)ethyl]-5-chloro-2,3-dihydro-2- methylbenzo[b]furan-7-carboxamide [(±)-1] were prepared from optically active benzyl 4-acetylamino-2,3-dihydro-2-methylbenzo[b]furan-7- carboxylate[(R)-(+)-6,(S)-(-)-6], respectively. The requisite (R)-(+)-6 and (S)-(-)-6 were prepared by large-scale preparative HPLC on chiral stationary phases (CSPs). The absolute configuration of (S)-(+)-1 was determined by single crystal X-ray analysis. The serotonin 5-HT4 receptor agonistic activity of (S)-(-)-1 hemifumarate (SK-951) which was hemifumarate of (S)- (+)-1 was about twice that of the other enantiomer (R)-(+)-1 hemifumarate which was hemifumarate of (R)-(-)-1.