title: Quinazolindione derivatives as potent 5-HT3A receptor antagonists.
abstract: 5-HT(3A) receptor antagonists have been used mainly for the treatment of nausea and vomiting. These days, the antagonists are of special interest due to their therapeutic potential to treat other diseases such as depression, psychotic disorder, drug abuse, and irritable bowel syndrome. To discover novel 5-HT(3A) receptor antagonists, we screened our in-house small molecule library, resulting in identifying the quinazolindione derivatives as potent 5-HT(3A) receptor antagonists. For the purpose of structure-activity relationship study, 24 quinazolindione analogues were biologically evaluated against 5-HT(3A) receptor. Among those, KKHT10612 shows the best antagonistic effect against 5-HT(3A) receptor with an IC(50) value of 0.8 microM which is comparable with that of the reference compound, MDL72222, and selectivity over T-type calcium channel as well.
authors.affiliation: Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University, Seoul, Republic of Korea.
authors.forename: Byung-Hwan
authors.initials: BH
authors.lastname: Lee
authors.forename: Min Jung
authors.initials: MJ
authors.lastname: Choi
authors.forename: Mi Na
authors.initials: MN
authors.lastname: Jo
authors.forename: Hee Jeong
authors.initials: HJ
authors.lastname: Seo
authors.forename: Seung-Yeol
authors.initials: SY
authors.lastname: Nah
authors.forename: Yong Seo
authors.initials: YS
authors.lastname: Cho
authors.forename: Ghilsoo
authors.initials: G
authors.lastname: Nam
authors.forename: Ae Nim
authors.initials: AN
authors.lastname: Pae
authors.forename: Hyewhon
authors.initials: H
authors.lastname: Rhim
authors.forename: Hyunah
authors.initials: H
authors.lastname: Choo
mesh_terms: D000818:Animals; D051379:Mice; D015394:Molecular Structure; D009865:Oocytes / Q000502:physiology; D010880:Piperidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D011799:Quinazolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D044406:Receptors, Serotonin, 5-HT3 / Q000378:metabolism*; D058831:Serotonin 5-HT3 Receptor Antagonists; D054852:Small Molecule Libraries / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014981:Xenopus
chemical_list: C543316:3-(4-methoxybenzyl)-N-(3-(2-piperidin-1-yl)ethyl)-2,4-dioxoquinazoline-7-carboxamide; D010880:Piperidines; D011799:Quinazolines; D044406:Receptors, Serotonin, 5-HT3; D058831:Serotonin 5-HT3 Receptor Antagonists; D054852:Small Molecule Libraries