title: A novel series of N-(hexahydro-1,4-diazepin-6-yl) and N-(hexahydroazepin- 3-yl)benzamides with high affinity for 5-HT3 and dopamine D2 receptors.
abstract: A novel series of benzamides with a hexahydro-1,4-diazepine or hexahydroazepine ring in the amine moiety were prepared, and their binding affinities for 5-HT3 and dopamine D2 receptors were evaluated. The R isomer of the 1-ethyl-4-methylhexahydro-1,4-diazepinylbenzamide (R)-22 had potent affinity for both receptors. The R-enantiomer of the corresponding 1-ethylhexahydroazepinylbenzamide 28 showed potent affinity for dopamine D2 receptors with reduced affinity for 5-HT3 receptors, while the S isomer was found to be a potent and selective 5-HT3 receptor antagonist.
authors.affiliation: Discovery Research Laboratories I, Dainippon Pharmaceutical Co., Ltd., Osaka, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Hirokawa
authors.forename: T
authors.initials: T
authors.lastname: Morie
authors.forename: H
authors.initials: H
authors.lastname: Yamazaki
authors.forename: N
authors.initials: N
authors.lastname: Yoshida
authors.forename: S
authors.initials: S
authors.lastname: Kato
mesh_terms: D000818:Animals; D001549:Benzamides / Q000378:metabolism*; D001665:Binding Sites; D002540:Cerebral Cortex / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism; D004294:Domperidone / Q000378:metabolism; D018492:Dopamine Antagonists / Q000378:metabolism; D007093:Imidazoles / Q000378:metabolism; D007211:Indoles / Q000378:metabolism; D008024:Ligands; D008787:Metoclopramide / Q000378:metabolism; D008956:Models, Chemical; D017294:Ondansetron / Q000378:metabolism; D051381:Rats; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000378:metabolism*; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists / Q000378:metabolism; D013134:Spiperone / Q000378:metabolism; D013237:Stereoisomerism
chemical_list: D001549:Benzamides; D018492:Dopamine Antagonists; D007093:Imidazoles; D007211:Indoles; D008024:Ligands; D017448:Receptors, Dopamine D2; D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists; C059068:GR 65630; D017294:Ondansetron; D013134:Spiperone; D004294:Domperidone; D008787:Metoclopramide