Syntheses and biological activities of optical isomers of 3-chloro-5-[3-(2-oxo-1,2,3,5,6,7,8,8a-octahydroimidazo[1,2-a]pyridine- 3-spiro-4'-piperidino)propyl]-10,11-dihydro-5H-dibenz[b,f]azepine (mosapramine) dihydrochloride.
Mosapramine (1) is a new neuroleptic drug with an asymmetric carbon atom (8a) in its imidazopyridine ring. The enantiomers of this agent were synthesized to compare their biological activities, such as antiapomorphine activity, affinity for dopamine D2 receptor and acute toxicity. The key intermediates, (R)-(-)- and (S)-(+)-2-oxo-1,2,3,5,6,7,8,8a-octahydroimidazo[1,2-a]pyridine- 3-spiro-4'-piperidines, were prepared by optical resolution of the corresponding (+/-)-compound and were treated with 3-chloro-5-(3-methanesulfonyloxypropyl)-10,11-dihydro-5H-dibenz[b, f]azepine to afford (R)-(-)-1 and (S)-(+)-1, respectively. There were few differences in the examined biological activities of the two enantiomers as their dihydrochlorides.
Tashiro
C
C
Research Laboratories, Yoshitomi Pharmaceutical Industries, Ltd., Fukuoka, Japan.
Setoguchi
S
S
Fukuda
T
T
Marubayashi
N
N
D000818:Animals; D014150:Antipsychotic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D001058:Apomorphine / Q000037:antagonists & inhibitors*; D001522:Behavior, Animal / Q000187:drug effects; D001552:Benzazepines / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D004285:Dogs; D004347:Drug Interactions; D005260:Female; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism*; D013237:Stereoisomerism; D014839:Vomiting / Q000139:chemically induced
D014150:Antipsychotic Agents; D001552:Benzazepines; D017448:Receptors, Dopamine D2; C046384:mosapramine; D001058:Apomorphine