Quinazolindione derivatives as potent 5-HT3A receptor antagonists

5-HT3A 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-HT3A receptor antagonists, we screened our in-house small molecule library, resulting in identifying the quinazolindione derivatives as potent 5-HT3A receptor antagonists. For the purpose of structure–activity relationship study, 24 quinazolindione analogues were biologically evaluated against 5-HT3A receptor. Among those, KKHT10612 shows the best antagonistic effect against 5-HT3A receptor with an IC50 value of 0.8 μM which is comparable with that of the reference compound, MDL72222, and selectivity over T-type calcium channel as well.

Novel 5-HT3A receptor antagonists were discovered and, among those, KKHT10612 shows the most potent antagonistic activity against 5-HT3A receptor and selectivity over T-type calcium channel.Figure optionsDownload as PowerPoint slide