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.
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.
Kakigami
T
T
General Research Park, Sanwa Kagaku Kenkyusho Co., Ltd., Mie, Japan.
Usui
T
T
Ikami
T
T
Tsukamoto
K
K
Miwa
Y
Y
Taga
T
T
Kataoka
T
T
D000818:Animals; D018360:Crystallography, X-Ray; D004947:Esophagus / Q000187:drug effects / Q000378:metabolism; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D051381:Rats; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D044422:Receptors, Serotonin, 5-HT4; D017366:Serotonin Receptor Agonists / Q000138:chemical synthesis* / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D044422:Receptors, Serotonin, 5-HT4