Quinazolindione derivatives as potent 5-HT3A receptor antagonists.
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.
Lee
Byung-Hwan
BH
Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University, Seoul, Republic of Korea.
Choi
Min Jung
MJ
Jo
Mi Na
MN
Seo
Hee Jeong
HJ
Nah
Seung-Yeol
SY
Cho
Yong Seo
YS
Nam
Ghilsoo
G
Pae
Ae Nim
AN
Rhim
Hyewhon
H
Choo
Hyunah
H
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
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